Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Jun 28;6(6):CD012721.
doi: 10.1002/14651858.CD012721.pub2.

Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction

Nicole Martin  1 , Karthick Manoharan, James Thomas, Ceri Davies, R Thomas Lumbers
Affiliations
Review

Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction

Nicole Martin et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Beta-blockers and inhibitors of the renin-angiotensin aldosterone system improve survival and reduce morbidity in people with heart failure with reduced left ventricular ejection fraction. There is uncertainty whether these treatments are beneficial for people with heart failure with preserved ejection fraction and a comprehensive review of the evidence is required.

Objectives: To assess the effects of beta-blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists in people with heart failure with preserved ejection fraction.

Search methods: We searched CENTRAL, MEDLINE, Embase and two clinical trial registries on 25 July 2017 to identify eligible studies. Reference lists from primary studies and review articles were checked for additional studies. There were no language or date restrictions.

Selection criteria: We included randomised controlled trials with a parallel group design enrolling adult participants with heart failure with preserved ejection fraction, defined by a left ventricular ejection fraction of greater than 40 percent.

Data collection and analysis: Two review authors independently selected studies for inclusion and extracted data. The outcomes assessed included cardiovascular mortality, heart failure hospitalisation, hyperkalaemia, all-cause mortality and quality of life. Risk ratios (RR) and, where possible, hazard ratios (HR) were calculated for dichotomous outcomes. For continuous data, mean difference (MD) or standardised mean difference (SMD) were calculated. We contacted trialists where neccessary to obtain missing data.

Main results: 37 randomised controlled trials (207 reports) were included across all comparisons with a total of 18,311 participants.Ten studies (3087 participants) investigating beta-blockers (BB) were included. A pooled analysis indicated a reduction in cardiovascular mortality (15% of participants in the intervention arm versus 19% in the control arm; RR 0.78; 95% confidence interval (CI) 0.62 to 0.99; number needed to treat to benefit (NNTB) 25; 1046 participants; 3 studies). However, the quality of evidence was low and no effect on cardiovascular mortality was observed when the analysis was limited to studies with a low risk of bias (RR 0.81; 95% CI 0.50 to 1.29; 643 participants; 1 study). There was no effect on all-cause mortality, heart failure hospitalisation or quality of life measures, however there is uncertainty about these effects given the limited evidence available.12 studies (4408 participants) investigating mineralocorticoid receptor antagonists (MRA) were included with the quality of evidence assessed as moderate. MRA treatment reduced heart failure hospitalisation (11% of participants in the intervention arm versus 14% in the control arm; RR 0.82; 95% CI 0.69 to 0.98; NNTB 41; 3714 participants; 3 studies; moderate-quality evidence) however, little or no effect on all-cause and cardiovascular mortality and quality of life measures was observed. MRA treatment was associated with a greater risk of hyperkalaemia (16% of participants in the intervention group versus 8% in the control group; RR 2.11; 95% CI 1.77 to 2.51; 4291 participants; 6 studies; high-quality evidence).Eight studies (2061 participants) investigating angiotensin converting enzyme inhibitors (ACEI) were included with the overall quality of evidence assessed as moderate. The evidence suggested that ACEI treatment likely has little or no effect on cardiovascular mortality, all-cause mortality, heart failure hospitalisation, or quality of life. Data for the effect of ACEI on hyperkalaemia were only available from one of the included studies.Eight studies (8755 participants) investigating angiotensin receptor blockers (ARB) were included with the overall quality of evidence assessed as high. The evidence suggested that treatment with ARB has little or no effect on cardiovascular mortality, all-cause mortality, heart failure hospitalisation, or quality of life. ARB was associated with an increased risk of hyperkalaemia (0.9% of participants in the intervention group versus 0.5% in the control group; RR 1.88; 95% CI 1.07 to 3.33; 7148 participants; 2 studies; high-quality evidence).We identified a single ongoing placebo-controlled study investigating the effect of angiotensin receptor neprilysin inhibitors (ARNI) in people with heart failure with preserved ejection fraction.

Authors' conclusions: There is evidence that MRA treatment reduces heart failure hospitalisation in heart failure with preserverd ejection fraction, however the effects on mortality related outcomes and quality of life remain unclear. The available evidence for beta-blockers, ACEI, ARB and ARNI is limited and it remains uncertain whether these treatments have a role in the treatment of HFpEF in the absence of an alternative indication for their use. This comprehensive review highlights a persistent gap in the evidence that is currently being addressed through several large ongoing clinical trials.

PubMed Disclaimer

Conflict of interest statement

NM: none known.

KM: none known.

JT: none known.

CD: has received sponsorship from Servier, Roche and Novartis to attend cardiology conferences, payment from GE Healthcare to give lectures on heart failure, and has served as a paid consultant to Servier and Vifor.

TL: has received research grants from Pfizer and has served as an unpaid consultant to GSK.

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Adamyan 2010 {published data only}
    1. Adamyan KG, Tumasyan LR. Independent and additive influence of statin and beta‐blocker on long‐term prognosis in patients with chronic heart failure and preserved systolic function. European Heart Journal 2010;31:850.
    1. Tumasyan LR, Adamyan KG. Influence of statin and beta‐blocker on long‐term prognosis in patients with chronic heart failure and preserved systolic function. European Journal of Heart Failure Supplements 2010;9:S23‐4.
ALDO‐DHF {published data only}
    1. Borlaug BA. Heart failure: Aldosterone antagonism for HFpEF. Nature Reviews Cardiology 2013;10(5):244‐6. - PubMed
    1. Djawid Hashemi D, Dettmann L, Trippel TD, Bobenko A, Gelbrich G, Lindhorst R, et al. Economic impact of heart failure with preserved ejection fraction: Insights from the prospective, randomized placebo‐controlled ALDO‐DHF trial. European Journal of Heart Failure 2017;19:155.
    1. Durstewitz K, Holzendorf V, Wachter R, Gelbrich G, Stahrenberg R, Hasenfuss G, et al. Galectin‐3 in heart failure with preserved ejection fraction‐the effects of chronic aldosterone receptor blockade (the ALDO‐DHF trial). Internist 2013;54(2):104‐5.
    1. Edelmann F, Gelbrich G, Duvinage A, Stahrenberg R, Behrens A, Prettin C, et al. Differential interaction of clinical characteristics with key functional parameters in heart failure with preserved ejection fraction‐‐results of the Aldo‐DHF trial. International Journal of Cardiology 2013;169(6):408‐17. - PubMed
    1. Edelmann F, Holzendorf V, Wachter R, Nolte K, Schmidt AG, Kraigher‐Krainer E, et al. Galectin‐3 in patients with heart failure with preserved ejection fraction: results from the Aldo‐DHF trial. European Journal of Heart Failure 2015;17(2):214‐23. - PubMed
AREA IN‐CHF {published and unpublished data}
    1. Boccanelli A, Caciatore G, Mureddu GF, Simone G, Clemenza F, Maria R, et al. Baseline characteristics of patients recruited in the AREA IN‐CHF study (Antiremodelling Effect of Aldosterone Receptors Blockade with Canrenone in Mild Chronic Heart Failure). Journal of Cardiovascular Medicine 2007;8(9):683‐91. - PubMed
    1. Boccanelli A, Mureddu GF, Cacciatore G, Clemenza F, Lenarda A, Gavazzi A, et al. Anti‐remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN‐CHF study): final results. European Journal of Heart Failure 2009;11(1):68‐76. - PubMed
    1. Cacciatore G, Boccanelli A, Mureddu GF, Maggioni AP, Latini R, Masson S, et al. The AREA IN‐CHF trial (antiremodeling effect of aldosterone receptors blockade with canrenone in mild chronic heart failure): rationale and design. Italian Heart Journal 2005;6(Suppl 1):66S‐74S. - PubMed
    1. Simone G, Chinali M, Mureddu GF, Cacciatore G, Lucci D, Latini R, et al. Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA‐in‐CHF study. Nutrition, Metabolism and Cardiovascular Diseases 2011;21(10):783‐91. - PubMed
    1. NCT00403910. Antiremodeling effect of aldosterone receptors blockade with canrenone in mild chronic heart failure. AREA IN‐CHF study [Phase 3 study of antiremodeling effect of aldosterone receptors blockade with canrenone in mild chronic heart failure]. clinicaltrials.gov/ct2/show/NCT00403910 (first received 27 November 2006.
Aronow 1993 {published data only}
    1. Aronow WS, Kronzon I. Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fraction. American Journal of Cardiology 1993;71(7):602‐4. - PubMed
Aronow 1997 {published data only}
    1. Aronow WS, Ahn C, Kronzon I. Effect of propranolol versus no propranolol on total mortality plus nonfatal myocardial infarction in older patients with prior myocardial infarction, congestive heart failure, and left ventricular ejection fraction > or = 40% treated with diuretics plus angiotensin‐converting enzyme inhibitors. American Journal of Cardiology 1997;80(2):207‐9. - PubMed
Aronow 1998 {published data only}
    1. Aronow WS, Mercando AD, Epstein S. Effect of benazepril on complex ventricular arrhythmias in older patients with congestive heart failure, prior myocardial infarction, and normal left ventricular ejection fraction. American Journal of Cardiology 1998;81(11):1368‐70. - PubMed
CandHeart {published data only}
    1. 2005‐001306‐87. Effects of Candesartan Cilexetil vs standard therapy on serum levels of brain natriuretic peptide in patients suffering from chronic heart failure with depressed and preserved systolic function. www.clinicaltrialsregister.eu/ctr‐search/trial/2005‐001306‐87/IT (first received 2 February 2007).
    1. Aleksova A, Masson S, Maggioni AP, Lucci D, Urso R, Staszewsky L, et al. Effects of candesartan on left ventricular function, aldosterone and BNP in chronic heart failure. Cardiovascular Drugs and Therapy 2012;26(6):131‐43. - PubMed
    1. NCT00843154. Efficacy of Candesartan on Brain Natriuretic Peptide Levels in Subjects With Chronic Heart Failure (CANDHEART) [Effects Of Candesartan Cilexetil vs Standard Therapy on Serum Levels of Brain Natriuretic Peptide in Patients Suffering From Chronic Heart Failure With Depressed and Preserved Systolic Function]. clinicaltrials.gov/ct2/show/NCT00843154 (First posted 13 February 2009).
CAN‐DHF {published data only}
    1. EudraCT 2007‐003070‐26. Candesartan “added” therapy for treatment optimization of symptomatic heart failure with diastolic dysfunction in diabetic and hypertensive patients. A randomized, placebo‐controlled, double‐blind, parallel‐group and multicentre clinical phase III study investigating the effects on NT‐proBNP over 6 months.. www.clinicaltrialsregister.eu/ctr‐search/trial/2007‐003070‐26/DE (first entered 10 July 2007).
    1. NCT00775840. Efficacy of candesartan on symptomatic heart failure in treating diabetic and hypertensive patients [Candesartan "added" therapy for treatment optimization of symptomatic heart failure with diastolic dysfunction in diabetic and hypertensive patients. A randomized, placebo‐controlled, double‐blind, parallel‐group and multicenter clinical phase III study investigating the effects on NT‐proBNP over 6 months]. clinicaltrials.gov/ct2/show/NCT00775840 (first received 20 October 2008).
CHARM‐Preserved {published data only}
    1. Badar AA, Perez‐Moreno AC, Hawkins NM, Brunton AP, Jhund PS, Wong CM, et al. Clinical characteristics and outcomes of patients with angina and heart failure in the CHARM (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity) Programme. European Journal of Heart Failure 2015;17(2):196‐204. - PubMed
    1. Bello NA, Claggett B, Desai AS, McMurray JJ, Granger CB, Yusuf S, et al. Influence of previous heart failure hospitalization on cardiovascular events in patients with reduced and preserved ejection fraction. Circulation 2014;7(4):590‐5. - PMC - PubMed
    1. Castagno D, Skali H, Takeuchi M, Swedberg K, Yusuf S, Granger CB, et al. Association of heart rate and outcomes in a broad spectrum of patients with chronic heart failure: results from the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and morbidity) program. Journal of the American College of Cardiology 2012;59(20):1785‐95. - PubMed
    1. Castagno D, Skali H, Takeuchi M, Swedberg K, Yusuf S, Granger CB, et al. Incidence and predictors of stroke in patients with chronic heart failure: Does left ventricular function Matter? Insights From the CHARM Program. Circulation 2011;124(Suppl 21):A17352.
    1. Chang SM, Granger CB, Johansson PA, Kosolcharoen P, McMurray JJ, Michelson EL, et al. Efficacy and safety of angiotensin receptor blockade are not modified by aspirin in patients with chronic heart failure: a cohort study from the Candesartan in Heart failure‐‐Assessment of Reduction in Mortality and morbidity (CHARM) programme. European Journal of Heart Failure 2010;12(7):738‐45. - PubMed
ELANDD {published data only}
    1. 2004‐000746‐20. Effects of the long‐term administration of nebivolol on the clinical symptoms, exercise capacity and left ventricular function of the patients with diastolic dysfunction (ELANDD). www.clinicaltrialsregister.eu/ctr‐search/search?query=eudract_number:200... (date submitted 9 October 2006).
    1. Conraads VM, Metra M, Kamp O, Keulenaer GW, Pieske B, Zamorano J, et al. Effects of the long‐term administration of nebivolol on the clinical symptoms, exercise capacity, and left ventricular function of patients with diastolic dysfunction: results of the ELANDD study. European Journal of Heart Failure 2012;14(2):219‐25. - PubMed
    1. Kamp O, Metra M, Keulenaer GW, Pieske B, Conraads V, Zamorano J, et al. Effect of the long‐term administration of nebivolol on clinical symptoms, exercise capacity and left ventricular function in patients with heart failure and preserved left ventricular ejection fraction: background, aims and design of the ELANDD study. Clinical Research in Cardiology 2010;99:75‐82. - PubMed
Hong Kong DHF {published data only}
    1. CUHK_CCT00035. Treatment of diastolic heart failure: the role of blockade of the renin‐angiotensin system. A comparison of diuretics with an angiotensin converting enzyme inhibitor, angiotensin receptor blockade or diuretics alone. www2.ccrb.cuhk.edu.hk/registry/public/15 (trial registration 7 September 2005).
    1. Yip GW, Wang M, Wang T, Chan S, Fung JW, Yeung L, et al. The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction. Heart 2008;94(5):573‐80. - PubMed
I‐PRESERVE {published data only}
    1. Adabag S, Rector TS, Anand IS, McMurray JJ, Zile M, Komajda M, et al. A prediction model for sudden cardiac death in patients with heart failure and preserved ejection fraction. European Journal of Heart Failure 2014;16(11):1175‐82. - PubMed
    1. Anand IS, Rector TS, Cleland JG, Kuskowski M, McKelvie RS, Persson H, et al. Prognostic value of baseline plasma amino‐terminal pro‐brain natriuretic peptide and its interactions with irbesartan treatment effects in patients with heart failure and preserved ejection fraction: findings from the I‐PRESERVE trial. Circulation 2011;4(5):569‐77. - PubMed
    1. Anonymous. Heart failure patients with preserved left ventricular ejection fraction did not benefit from additional ARB therapy. Cardiovascular Journal of Africa 2008;19(6):337‐9. - PubMed
    1. Badar AA, Perez‐Moreno AC, Hawkins NM, Jhund PS, Brunton AP, et al. Clinical characteristics and outcomes of patients with coronary artery disease and angina: analysis of the irbesartan in patients with heart failure and preserved systolic function trial. Circulation 2015;8(4):717‐24. - PubMed
    1. Blandon JA. ARBs and the impact of worsening renal function in heart failure patients with preserved EF. Cardiology Review 2014;30(6):no pagination.
J‐DHF {published data only}
    1. Hori M. Rationale and design of a randomized trial to assess the effects of β‐blocker in diastolic heart failure; Japanese Diastolic Heart Failure Study (J‐DHF). Journal of Cardiac Failure 2005;11(7):542‐7. - PubMed
    1. UMIN: C000000318. Japanese Diastolic Heart Failure Study. upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000000411 (Registered 1 February 2006).
    1. Yamamoto K, Origasa H, Hori M. Effects of carvedilol on heart failure with preserved ejection fraction: the Japanese Diastolic Heart Failure Study (J‐DHF). European Journal of Heart Failure 2013;15(1):110‐8. - PubMed
    1. Yamamoto K, Origasa H, Hori M. Left atrial dilatation as a predictive factor of beneficial response to carvedilol in patients with HFPEF: A finding from the Japanese Diastolic Heart Failure study (J‐DHF). European Heart Journal 2013;34:161.
    1. Yamamoto K, Origasa H, Suzuki Y, Takahashi T, Shinozaki T, Watanabe T, et al. Relation of risk factors with response to carvedilol in heart failure with preserved ejection fraction ‐ a report from the Japanese Diastolic Heart Failure Study (J‐DHF). Journal of Cardiology 2014;63(6):424‐31. - PubMed
Karapysh 2015 {published data only}
    1. Karapysh VA, Vatutin NT, Shevelok AN. Effects of spironolactone on the left ventricular hypertrophy in chronic heart failure with preserved ejection fraction. European Journal of Heart Failure 2015;17:48.
Kasama 2005 {published data only}
    1. Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, et al. Effects of candesartan on cardiac sympathetic nerve activity in patients with congestive heart failure and preserved left ventricular ejection fraction. Journal of the American College of Cardiology 2005;45(5):661‐7. - PubMed
Kitzman 2010 {published data only}
    1. Kitzman DW, Hundley WG, Brubaker PH, Morgan TM, Moore JB, Stewart KP, et al. A randomized double‐blind trial of enalapril in older patients with heart failure and preserved ejection fraction: effects on exercise tolerance and arterial distensibility. Circulation 2010;3(4):477‐85. - PMC - PubMed
    1. NCT01411735. Evaluation of enalapril versus placebo in patients with diastolic heart failure (PIE‐I). clinicaltrials.gov/show/NCT01411735 (first posted 8 August 2011).
Kurrelmeyer 2014 {published and unpublished data}
    1. Kurrelmeyer KM, Ashton Y, Xu J, Nagueh SF, Torre‐Amione G, Deswal A. Effects of spironolactone treatment in elderly women with heart failure and preserved left ventricular ejection fraction. Journal of Cardiac Failure 2014;20(8):560‐8. - PubMed
    1. NCT00206232. Novel treatment for diastolic heart failure in women. clinicaltrials.gov/show/NCT00206232 (first posted 21 September 2005).
Mak 2009 {published data only}
    1. Mak G, Ledwidge M, Murphy NF, Phelan D, Dawkins I, Watson C, et al. Eplerenone favourably alters collagen metabolism in diastolic heart failure. European Heart Journal 2009;30:866.
    1. Mak GJ, Ledwidge MT, Watson CJ, Phelan DM, Dawkins IR, Murphy N, et al. Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone. Journal of the American College of Cardiology 2009;54(18):1674‐82. - PubMed
    1. NCT00505336. The effect of eplerenone and atorvastatin on markers of collagen turnover in diastolic heart failure. clinicaltrials.gov/show/NCT00505336 (first posted 23 July 2007).
Mittal 2017 {published and unpublished data}
    1. CTRI/2010/091/000438. Evaluation of efficacy and safety of metoprolol in patients having heart failure with normal ejection fraction: a randomised, double‐blind, placebo‐controlled trial [A clinical trial to study the efficacy and safety of metoprolol in heart failure with normal ejection fraction]. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=1626 (registered on 19 May 2010).
    1. Mittal N, Shafiq N, Reddy S, Malhotra S, Kumari S, Varma S. Evaluation of efficacy of metoprolol in patients having heart failure with preserved ejection fraction: A randomized, double‐blind, placebo‐controlled pilot trial. Perspectives in Clinical Research 2017;8(3):124‐31. - PMC - PubMed
Mottram 2004 {published data only}
    1. Mottram PM, Haluska B, Leano R, Cowley D, Stowasser M, Marwick TH. Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure. Circulation 2004;110:558‐65. - PubMed
    1. Mottram PM, Haluska BA, Leano R, Cowley D, Stowasser M, Marwick TH. Myocardial dysfunction in hypertensive patients with isolated diastolic heart failure is reversible.A randomized trial of aldosterone antagonism. European Heart Journal 2004;25(Suppl S):47‐8. - PubMed
Orea‐Tejeda 2007 {published data only}
    1. Orea‐Tejeda A, Colin‐Ramirez E, Castillo‐Martinez L, Asensio‐Lafuente E, Corzo‐Leon D, Gonzalez‐Toledo R, et al. Aldosterone receptor antagonists induce favorable cardiac remodeling in diastolic heart failure patients. Revista de Investigacion Clinica 2007;59(2):103‐7. - PubMed
Parthasarathy 2009 {published and unpublished data}
    1. CVAL489B2401. Novartis Clinical Trial Results Database. www.novctrd.com/CtrdWeb/displaypdf.nov?trialresultid=2460 (date accessed 30 November 2017).
    1. NCT00171106. Efficacy and safety of valsartan versus placebo on exercise tolerance in patients with heart failure [A double‐blind, randomised, placebo‐controlled, parallel group study to determine the effects of valsartan on exercise time in subjects with symptomatic diastolic heart failure]. clinicaltrials.gov/show/NCT00171106 (first posted 15 September 2005).
    1. Parthasarathy HK, Pieske B, Weisskopf M, Andrews CD, Brunel P, Struthers AD, et al. A randomized, double‐blind, placebo‐controlled study to determine the effects of valsartan on exercise time in patients with symptomatic heart failure with preserved ejection fraction. European Journal of Heart Failure 2009;11(10):980‐9. - PMC - PubMed
PEP‐CHF {published data only}
    1. Cleland JG, Taylor J, Freemantle N, Goode KM, Rigby AS, Tendera M. Relationship between plasma concentrations of N‐terminal pro brain natriuretic peptide and the characteristics and outcome of patients with a clinical diagnosis of diastolic heart failure: a report from the PEP‐CHF study. European Journal of Heart Failure 2012;14(5):487‐94. - PubMed
    1. Cleland JG, Tendera M, Adamus J, Freemantle N, Gray CS, Lye M, et al. Perindopril for elderly people with chronic heart failure: the PEP‐CHF study. European Journal of Heart Failure 1999;1(3):211‐7. - PubMed
    1. Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J. The perindopril in elderly people with chronic heart failure (PEP‐CHF) study. European Heart Journal 2006;27(16):2338‐45. - PubMed
    1. McMurray J. Renin angiotensin blockade in heart failure with preserved ejection fraction: The signal gets stronger. European Heart Journal 2006;27(19):2257‐9. - PubMed
    1. Widimsky J. Managing diastolic heart failure. Results of PEP‐CHF [Lecba diastolickeho srdecniho selhani. Vysledky studie PEP‐CHF]. Cor Vasa 2006;48(11):403‐7.
RAAM‐PEF {published and unpublished data}
    1. Deswal A, Richardson P, Bozkurt B, Mann DL. Results of the Randomized Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction trial (RAAM‐PEF). Journal of Cardiac Failure 2011;17(8):634‐42. - PubMed
    1. NCT00108251. Aldosterone antagonism in diastolic heart failure. clinicaltrials.gov/ct2/show/NCT00108251 (first posted 15 April 2005).
Sahoo 2016 {published data only}
    1. Sahoo D, Kapoor A, Sinha A, Khanna R, Kumar S, Garg N, et al. Targeting the sympatho‐adrenergic link in chronic rheumatic mitral regurgitation: assessing the role of oral beta‐blockers. Cardiovascular Therapeutics 2016;34(4):261‐7. - PubMed
SENIORS {published data only}
    1. Cohen‐Solal A, Kotecha D, Veldhuisen DJ, Babalis D, Bohm M, Coats AJ, et al. Efficacy and safety of nebivolol in elderly heart failure patients with impaired renal function: insights from the SENIORS trial. European Journal of Heart Failure 2009;11(9):872‐80. - PMC - PubMed
    1. Flather MD, Shibata MC, Coats AJS, Veldhuisen DJ, Parkhomenko A, Borbola J, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). European Heart Journal 2005;26:215‐25. - PubMed
    1. Ghio S, Magrini G, Serio A, Klersy C, Fucili A, Ronaszeki A, Karpati P, et al. Effects of nebivolol in elderly heart failure patients with or without systolic left ventricular dysfunction: results of the SENIORS echocardiographic substudy. European Heart Journal 2006;27(5):562‐8. - PubMed
    1. Lindsey ML, Freeman GL. Beta‐blockade in heart failure: adding SENIORS to the mix. European Heart Journal 2006;27(5):506‐7. - PubMed
    1. Montero‐Perez‐Barquero M, Flather M, Roughton M, Coats A, Bohm M, Veldhuisen DJ, et al. Influence of systolic blood pressure on clinical outcome in elderly heart failure patients with preserved and reduced ejection fraction treated with nebivolol: data from SENIORS trial. European Heart Journal 2014;35:339. - PubMed
Shu 2005 {published data only}
    1. Shu M, Xi R, Zhang P, He G, Song Z, Chi L, et al. Short‐term and long‐term effects of bisoprolol on chronic heart failure related to rheumatic heart disease and atrial fibrillation. Pharmacy and Therapeutics 2005;30(7):400‐7.
SNEGOVIK {published data only}
    1. Mareev V, Skvortsov A, Danielyan M, Belenkov YU. Quinapril in treatment of ambulatory patients with arterial hypertension and congestive heart failure and preserved systolic left ventricular function. (Results from the SNEGOVIK Study). European Journal of Heart Failure. Supplement 2011;10:S78.
STRUCTURE {published data only}
    1. ACTRN12614000088640. Spironolactone in myocardial dysfunction with reduced exercise capacity [Effects of spironolactone or control on LV filling pressure and exercise capacity in patients with myocardial dysfunction with reduced exercise capacity]. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365563 (data submitted 6 January 2014).
    1. Kosmala W, Rojek A, Przewlocka‐Kosmala M, Wright L, Mysiak A, Marwick TH. Beneficial effect of aldosterone antagonism on exercise tolerance in heart failure with preserved ejection fraction‐SpironolacTone in myocaRdial dysfunction with reduced exercise capacity (STRUCTURE). European Heart Journal 2016;37:795. - PubMed
    1. Kosmala W, Rojek A, Przewlocka‐Kosmala M, Wright L, Mysiak A, Marwick TH. Effect of aldosterone antagonism on exercise tolerance in heart failure with preserved ejection fraction. Journal of the American College of Cardiology 2016;68(17):1823‐34. - PubMed
SUPPORT {published data only}
    1. Miura M, Sakata Y, Miyata S, Shiba N, Takahashi J, Nochioka K, et al. Influence of left ventricular ejection fraction on the effects of supplemental use of angiotensin receptor blocker olmesartan in hypertensive patients with heart failure. Circulation Journal 2016;80(10):2155‐64. - PubMed
    1. Miura M, Sakata Y, Miyata S, Tadaki S, Ushigome R, Yamouchi T, et al. The supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial. Journal of Cardiac Failure 2015;21(10):S159. - PubMed
    1. NCT00417222. Supplemental benefit of angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT). clinicaltrials.gov/ct2/show/NCT00417222 (first posted 29 December 2006).
    1. Sakata Y, Shiba N, Takahashi J, Miyata S, Nochioka K, Miura M, et al. Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: The supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial. European Heart Journal 2015;36(15):915‐23. - PMC - PubMed
SWEDIC {published data only}
    1. Bergstrom A, Andersson B, Edner M, Nylander E, Persson H, Dahlstrom U. Effect of carvedilol on diastolic function in patients with diastolic heart failure and preserved systolic function. Results of the Swedish Doppler‐echocardiographic study (SWEDIC). European Journal of Heart Failure 2004;6(4):453‐61. - PubMed
Takeda 2004 {published data only}
    1. Takeda Y, Fukutomi T, Suzuki S, Yamamoto K, Ogata M, Kondo H, et al. Effects of carvedilol on plasma B‐type natriuretic peptide concentration and symptoms in patients with heart failure and preserved ejection fraction. American Journal of Cardiology 2004;94:448‐53. - PubMed
TOPCAT {published data only}
    1. Anand IS, Claggett B, Liu J, Shah AM, Rector TS, Shah SJ, et al. Interaction between spironolactone and natriuretic peptides in patients with heart failure and preserved ejection fraction: from the TOPCAT trial. JACC. Heart Failure 2017;5(4):241‐52. - PubMed
    1. Anand IS, Solomon SD, Claggett B, Shah SJ, O'Meara E, Boineau R, et al. Prognostic value of baseline BNP and NT‐proBNP and its interaction with spironolactone in patients with heart failure and preserved ejection fraction in the TOPCAT trial. Circulation 2015;132:no pagination.
    1. Bajaj NS, Claggett B, Lewis E, Desai A, Fang J, Omeara E, et al. Influence of left ventricular ejection fraction on cause‐specific mortality in heart failure with preserved ejection fraction: The TOPCAT trial. Journal of the American College of Cardiology 2017;69(11):884.
    1. Bristow MR, Enciso JS, Gersh BJ, Grady C, Rice MM, Singh S, et al. Detection and management of geographic disparities in the TOPCAT trial: lessons learned and derivative recommendations. JACC: Basic to Translational Science 2016;1(3):180‐9. - PMC - PubMed
    1. Desai AS, Lewis EF, Li R, Solomon SD, Assmann SF, Boineau R, et al. Rationale and design of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction. American Heart Journal 2011;162(6):966‐72. - PubMed
Upadhya 2017 {published and unpublished data}
    1. NCT00123955. PIE II: pharmacological intervention in the elderly II [Exercise intolerance in elderly diastolic heart failure]. clinicaltrials.gov/show/NCT00123955 (first posted 26 July 2005).
    1. Upadhya B, Hundley WG, Brubaker PH, Morgan TM, Stewart KP, Kitzman DW. Effect of spironolactone on exercise tolerance and arterial function in older adults with heart failure with preserved ejection fraction. Journal of the American Geriatric Society 2017;19:19. - PMC - PubMed
Wang 2010 {published data only}
    1. Wang YC, Yu CC, Chiu FC, Tsai CT, Lai LP, Hwang JJ, et al. Aldosterone antagonism increases post‐exercise recruitment of systolic myocardial motion over left ventricular lateral wall in hypertensive patients with diastolic heart failure. Circulation 2010;122(2):P1059.
Yuksek 2012 {published data only}
    1. Yuksek U, Hamza D, Zehra A, Ugur K, Nihan KE, Rida B, et al. The effect of perindopril treatment on echocardiographic diastolic and systolic functional parameters and serum NT‐proBNP values in diastolic heart failure patients. European Journal of Heart Failure. Supplements 2012;11:S231.
Zi 2003 {published data only}
    1. Zi M, Carmichael N, Lye M. The effect of quinapril on functional status of elderly patients with diastolic heart failure. Cardiovascular Drugs and Therapy 2003;17:133‐9. - PubMed

References to studies excluded from this review

ACTRN12610001087044 {published data only}
    1. ACTRN12610001087044. Use of exercise and medical therapies to improve cardiac function among patients with exertional shortness of breath due to lung congestion. www.anzctr.org.au/ACTRN12610001087044.aspx (date received 13 December 2010).
    1. Kosmala W, Holland DJ, Rojek A, Wright L, Przewlocka‐Kosmala M, Marwick TH. Effect of If‐channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial. Journal of the American College of Cardiology 2013;62(15):1330‐8. - PubMed
Adgey 1992 {published data only}
    1. Adgey J, Clarke M, Raza A, Meddis D. Study of the safety and efficacy of ACE inhibitors and their effects on 24‐hour electrocardiographic monitoring in the treatment of moderate‐to‐severe heart failure: an interim analysis. American Journal of Cardiology 1992;70(10):142C‐4C. - PubMed
Ammon 2001 {published data only}
    1. Ammon S. Managing patients with heart failure. American Journal of Nursing 2001;101(12):34‐40. - PubMed
Andersson 1996 {published data only}
    1. Andersson B, Caidahl K, Lenarda A, Warren SE, Goss F, Waldenstrom A, et al. Changes in early and late diastolic filling patterns induced by long‐term adrenergic beta‐blockade in patients with idiopathic dilated cardiomyopathy. Circulation 1996;94(4):673‐82. - PubMed
Andersson 1999 {published data only}
    1. Andersson B, Stromblad SO, Lomsky M, Waagstein F. Heart rate dependency of cardiac performance in heart failure patients treated with metoprolol. European Heart Journal 1999;20(8):575‐83. - PubMed
Andersson 2000 {published data only}
    1. Andersson B, Waagstein F, Caidahl K, Eurenius I, Tang MS, Wikh R. Early changes in longitudinal performance predict future improvement in global left ventricular function during long term beta adrenergic blockade. Heart 2000;84(6):599‐605. - PMC - PubMed
Anonymous 1996 {published data only}
    1. Anonymous. Effectiveness of spironolactone added to an angiotensin‐converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (the Randomized Aldactone Evaluation Study [RALES]). American Journal of Cardiology 1996;78(8):902‐7. - PubMed
Anonymous 1999 {published data only}
    1. Anonymous. Heart failure management in primary care: implications of the ATLAS study. International Journal of Clinical Practice. Supplement 1999;100:25‐30. - PubMed
Anonymous 2000 {published data only}
    1. Anonymous. Effects of metoprolol CR in patients with ischemic and dilated cardiomyopathy : the randomized evaluation of strategies for left ventricular dysfunction pilot study. Circulation 2000;101(4):378‐84. - PubMed
Anonymous 2001 {published data only}
    1. Anonymous. Carvedilol saves lives ‐ new data from landmark trials prove survival benefits in heart failure and post myocardial infarction. Cardiovascular Journal of South Africa 2001;12(2):122‐3. - PubMed
Anonymous 2002 {published data only}
    1. Anonymous. Stress intolerance in diastolic dysfunction. A case for AT1 blocker?. MMW Fortschritte der Medizin 2002;144(1‐2):69. - PubMed
Anonymous 2003 {published data only}
    1. Anonymous. When after myocardial infarction a pump weakness remains. ACE inhibitors and AT‐1 blockers equivalent. MMW Fortschritte der Medizin 2003;145(49):18‐9. - PubMed
Anonymous 2003a {published data only}
    1. Anonymous. CHARM shows benefits of Atacand for symptomatic heart failure. Cardiovascular Journal of South Africa 2003;14(5):284. - PubMed
Anonymous 2003b {published data only}
    1. Anonymous. Heart failure symptoms despite normal pump function. Beta blockers also improve diastole. MMW Fortschritte der Medizin 2003;145(26):58. - PubMed
Anonymous 2003c {published data only}
    1. Anonymous. NMR shows how beta blockers change the failing ventricle. Decreased size and better output performance. MMW Fortschritte der Medizin 2003;145(25):56. - PubMed
Anonymous 2005 {published data only}
    1. Anonymous. Heart failure after acute myocardial infarct. Early aldosterone blockade increases survival rate. MMW Fortschritte der Medizin 2005;147(27‐28):44. - PubMed
Anonymous 2008 {published data only}
    1. Anonymous. Diastolic heart failure: AT1 blocker without effect. MMW Fortschritte der Medizin 2008;150(47):13. - PubMed
Anonymous 2008a {published data only}
    1. Anonymous. Misdiagnosed emergency: heart failure symptoms after infarct. Rapid aldosterone block can safe the tired heart. MMW Fortschritte der Medizin 2008;150(22):48‐9. - PubMed
Anonymous 2013 {published data only}
    1. Anonymous. Spironolactone made no difference to patients with mild diastolic heart failure. BMJ 2013;346:f1290. - PubMed
ANZ HF carvedilol {published data only}
    1. Australia/New Zealand Heart Failure Research Collaborative Group. Randomised, placebo‐controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Lancet 1997;349(9049):375‐80. - PubMed
    1. Australia–New Zealand Heart Failure Research Collaborative Group. Effects of carvedilol, a vasodilator‐beta‐blocker, in patients with congestive heart failure due to ischemic heart disease. Australia‐New Zealand Heart Failure Research Collaborative Group. Circulation 1995;92(2):212‐8. - PubMed
    1. Doughty RN, Whalley GA, Gamble G, MacMahon S, Sharpe N. Effects of carvedilol on left ventricular regional wall motion in patients with heart failure caused by ischemic heart disease. Journal of Cardiac Failure 2000;6(1):11‐8. - PubMed
    1. Doughty RN, Whalley GA, Gamble G, MacMahon S, Sharpe N. Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease. Australia‐New Zealand Heart Failure Research Collaborative Group. Journal of the American College of Cardiology 1997;29(5):1060‐6. - PubMed
    1. Krum H, Shusterman N, MacMahon S, Sharpe N. Efficacy and safety of carvedilol in patients with chronic heart failure receiving concomitant amiodarone therapy. Australia/New Zealand Heart Failure Research Collaborative Group. Journal of Cardiac Failure 1998;4(4):281‐8. - PubMed
Aoyama 2007 {published data only}
    1. Aoyama N. Effect of combination therapy with angiotensin II type I receptor and aldosterone receptor blockers in heart failure. Nippon Rinsho 2007;65(Suppl 5):145‐9. - PubMed
Apostolovic 2013 {published data only}
    1. Apostolovic S, Stanojevic D, Jankovic‐Tomasevic R, Salinger‐Martinovic S, Djordjevic‐Radojkovic D, Pavlovic M, et al. Influence of optimal beta blocker therapy on biomarkers of inflammation and proliferation in elderly patients with chronic stable heart failure. European Journal of Heart Failure 2013;12:S200.
Apostolovic 2014a {published data only}
    1. Apostolovic S, Stanojevic D, Jankovic‐Tomasevic R, Salinger‐Martinovic S, Pavlovic M, Djordjevic‐Radojkovic D, et al. Beta‐blockers in heart failure‐influence on left ventricle remodeling. CIBIS ELD sub‐study. European Heart Journal Cardiovascular Imaging 2014;15:ii213.
Apostolovic 2014b {published data only}
    1. Apostolovic S, Stanojevic D, Salinger‐Martinovic S, Jankovic‐ Tomasevic R, Djordjevic‐Radojkovic D, Pavlovic M, et al. Influence of optimization of beta blocker therapy in heart failure patients on natriuretic peptide levels and exercise capacity. European Heart Journal: Acute Cardiovascular Care 2014;3(2):176.
Arena 2007 {published data only}
    1. Arena RA, Guazzi M, Myers J, Abella J. The prognostic value of ventilatory efficiency with beta‐blocker therapy in heart failure. Medicine & Science in Sports & Exercise 2007;39(2):213‐9. - PubMed
Armstrong 1999 {published data only}
    1. Armstrong PW. Improved outcome in heart failure. International Journal of Clinical Practice. Supplement 1999;100:10‐1. - PubMed
Aronow 1991 {published data only}
    1. Aronow WS. Digoxin or angiotensin converting enzyme inhibitors for congestive heart failure in geriatric patients. Which is the preferred treatment?. Drugs and Aging 1991;1(2):98‐103. - PubMed
Aronow 2001 {published data only}
    1. Aronow WS, Ahn C, Kronzon I. Effect of beta blockers alone, of angiotensin‐converting enzyme inhibitors alone, and of beta blockers plus angiotensin‐converting enzyme inhibitors on new coronary events and on congestive heart failure in older persons with healed myocardial infarcts and asymptomatic left ventricular systolic dysfunction. American Journal of Cardiology 2001;88(11):1298‐300. - PubMed
Axelsson 2015 {published data only}
    1. Axelsson A, Iversen K, Vejlstrup N, Ho C, Havndrup O, Jensen M K, et al. The effect of losartan on diastolic function, exercise capacity and symptoms in hypertrophic cardiomyopathy. JACC 2015;65(10):A857.
Balaban 2007 {published data only}
    1. Balaban Y, Ozhan H, Albayrak S, Kaya A, Ordu, Yazici M. Efficacy of spiranolactone therapy in patients with impaired left ventricular filling [Sol ventrikul doluzu bozulmus hastalarda spironolakton tedavisinin etkinligi]. MN Kardiyoloji 2007;14(3):182‐6.
Bao 2005 {published data only}
    1. Bao ZH, Han Y, Sheng ZS. Carvedilol for the intervention of the cardiac function and exercise tolerance in patients with congestive heart failure. Chinese Journal of Clinical Rehabilitation 2005;9(15):53‐5.
Barr 1995 {published data only}
    1. Barr CS, Lang CC, Hanson J, Arnott M, Kennedy N, Struthers AD. Effects of adding spironolactone to an angiotensin‐converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease. American Journal of Cardiology 1995;76(17):1259‐65. - PubMed
Barrios 2009 {published data only}
    1. Barrios V, Escobar C, Echarri R. Letter by Barrios et al regarding article, "Heart failure with preserved and reduced left ventricular ejection fraction in the antihypertensive and lipid‐lowering treatment to prevent heart attack trial". Circulation 2009;120(5):e31. - PubMed
Barry 2003 {published data only}
    1. Barry WH, Gilbert EM. How do beta‐blockers improve ventricular function in patients with congestive heart failure?. Circulation 2003;107(19):2395‐7. - PubMed
Bartels 1999 {published data only}
    1. Bartels Gl, Heuvel FM, Veldhuisen DJ, Ent M, Remme WJ. Acute anti‐ischemic effects of perindoprilat in men with coronary artery disease and their relation with left ventricular function. American Journal of Cardiology 1999; Vol. 83, issue 3:332‐6. - PubMed
Baruch 1999 {published data only}
    1. Baruch L, Anand I, Cohen IS, Ziesche S, Judd D, Cohn JN. Augmented short‐ and long‐term hemodynamic and hormonal effects of an angiotensin receptor blocker added to angiotensin converting enzyme inhibitor therapy in patients with heart failure. Vasodilator Heart Failure Trial (V‐HeFT) Study Group. Circulation 1999;99(20):2658‐64. - PubMed
Baruch 2004 {published data only}
    1. Baruch L, Glazer RD, Aknay N, Vanhaecke J, Heywood JT, Anand I, et al. Morbidity, mortality, physiologic and functional parameters in elderly and non‐elderly patients in the Valsartan Heart Failure Trial (Val‐HeFT). American Heart Journal 2004;148(6):951‐7. - PubMed
Bauersachs 2004 {published data only}
    1. Bauersachs J. Aldosterone antagonism in heart failure: improvement of cardiac remodelling, endothelial dysfunction and platelet activation. European Journal of Clinical Investigation 2004;34(10):649‐52. - PubMed
Baumhakel 2008 {published data only}
    1. Baumhakel M, Muller U, Bohm M. Valsartan improves symptoms and quality of life in patients with chronic heart failure. MMW Fortschritte der Medizin 2008;150(Suppl 1):48‐53. - PubMed
Bellenger 2004 {published data only}
    1. Bellenger NG, Rajappan K, Rahman SL, Lahiri A, Raval U, Webster J, et al. Effects of carvedilol on left ventricular remodelling in chronic stable heart failure: a cardiovascular magnetic resonance study. Heart 2004;90(7):760‐4. - PMC - PubMed
Berry 2001 {published data only}
    1. Berry C, Norrie J, McMurray JJV. Are angiotensin II receptor blockers more efficacious than placebo in heart failure? Implications of ELITE‐2. American Journal of Cardiology 2001;87(5):606‐7. - PubMed
Bettencourt 1999 {published data only}
    1. Bettencourt P. Treating diastolic heart failure: the role of ACE inhibitors. Revista Portuguesa de Cardiologia 1999;18(Suppl 5):V101‐6. - PubMed
Beygui 2016 {published data only}
    1. Beygui F, Cayla G, Roule V, Roubille F, Delarche N, Silvain J, et al. Early aldosterone blockade in acute myocardial infarction: The ALBATROSS randomized clinical trial. Journal of the American College of Cardiology 2016;67(16):1917‐27. - PubMed
Blagodar 2003 {published data only}
    1. Blagodar VN, Petrii VV, Makolkin VI. Effect of lisinopril on cardiac remodeling in patients with cardiosclerosis after myocardial infarction and signs of chronic heart failure. Kardiologiia 2003;43(9):17‐20. - PubMed
Blomer 1990 {published data only}
    1. Blomer H. Treatment of heart failure: what ‐ when ‐ how?. Verhandlungen Der Deutschen Gesellschaft Fur Innere Medizin 1990;96:157‐67. - PubMed
Borghi 2011 {published data only}
    1. Borghi C. Double‐blind, randomized comparison of zofenopril vs. ramipril in MI patients treated with ASA: The SMILE 4 study and subgroup analysis. Circulation 2011;124(21):no pagination.
Borgi 1990 {published data only}
    1. Borgi C, Magelli C, Costa FV, Magnani B, Ambrosioni E. Captopril improves hemodynamic response to static exercise in patients with congestive heart failure: a double‐blind, placebo‐controlled, randomized trial. Clinical Cardiology 1990;13(5):329‐34. - PubMed
Borlaug 2014 {published data only}
    1. Borlaug BA. MY APPROACH to heart failure with preserved ejection fraction. Trends in Cardiovascular Medicine 2014;24(8):369‐70. - PubMed
Bornkessel 1992 {published data only}
    1. Bornkessel B, Heinzl S. ACE‐inhibitors and heart failure. Results of studies of left ventricular dysfunction. Medizinische Monatsschrift für Pharmazeuten 1992;15(3):76‐80. - PubMed
Bounhoure 1991 {published data only}
    1. Bounhoure J P. Perindopril and chronic heart failure. Archives Des Maladies Du Coeur Et Des Vaisseaux 1991;84(Spec No 4):89‐92. - PubMed
Braunwald 2004 {published data only}
    1. Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J, et al. Angiotensin‐converting‐enzyme inhibition in stable coronary artery disease. New England Journal of Medicine 2004;351(20):2058‐68. - PMC - PubMed
Brilla 1989 {published data only}
    1. Brilla CG, Kramer B, Hoffmeister HM, Muller‐Schauenburg W, Risler T, Seipel L. Low‐dose enalapril in severe chronic heart failure. Cardiovascular Drugs and Therapy 1989;3(2):211‐8. - PubMed
Brilla 1991 {published data only}
    1. Brilla CG, Kramer B, Risler T, Seipel L. Low‐dose enalapril in severe chronic heart failure [Niedrigdosiertes Enalapril bei schwerer chronischer Herzinsuffizienz]. Zeitschrift für Kardiologie 1991;80(Suppl 2):44‐9. - PubMed
Bristow 1994 {published data only}
    1. Bristow MR, O'Connell JB, Gilbert EM, French WJ, Leatherman G, Kantrowitz NE, et al. Dose‐response of chronic beta‐blocker treatment in heart failure from either idiopathic dilated or ischemic cardiomyopathy. Bucindolol Investigators. Circulation 1994;89(4):1632‐42. - PubMed
Bristow 1996 {published data only}
    1. Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al. Carvedilol produces dose‐related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation 1996;94(11):2807‐16. - PubMed
Bussmann 1987 {published data only}
    1. Bussmann WD, Storger H, Hadler D, Reifart N, Fassbinder W, Jungmann E, et al. Long‐term treatment of severe chronic heart failure with captopril: a double‐blind, randomized, placebo‐controlled, long‐term study. Journal of Cardiovascular Pharmacology 1987;9(Suppl 2):S50‐60. - PubMed
Butler 2017 {published data only}
    1. Butler J, Anstrom KJ, Felker GM, Givertz MM, Kalogeropoulos AP, Konstam MA, et al. Efficacy and safety of spironolactone in acute heart failure: the ATHENA‐HF randomized clinical trial. JAMA Cardiology 2017;2(9):950‐8. - PMC - PubMed
    1. Butler J, Hernandez AF, Anstrom KJ, Kalogeropoulos A, Redfield MM, Konstam MA, et al. Rationale and design of the ATHENA‐HF trial: aldosterone targeted neurohormonal combined with natriuresis therapy in heart failure. Journal of the American College of Cardiology. Heart Failure 2016;4(9):726‐35. - PMC - PubMed
    1. NCT02235077. Study of high‐dose spironolactone vs placebo therapy in acute heart failure (ATHENA‐HF). clinicaltrials.gov/show/NCT02235077 (first received 9 September 2014).
Cafaro 2010 {published data only}
    1. Cafaro B, Barr S, Brand JL. Question: does beta‐blocker therapy improve outcomes in patients with congestive heart failure with normal left ventricular function (diastolic dysfunction)?. Journal of the Oklahoma State Medical Association 2010;103(2):51‐2. - PubMed
Cardoso 1999 {published data only}
    1. Cardoso JS. Treating diastolic heart failure: the role of beta‐blockers. Revista Portuguesa de Cardiologia 1999;18(Suppl 5):V97‐9. - PubMed
Castagno 2010 {published data only}
    1. Castagno D, Jhund PS, Weir CJ, Colucci WS, Lopez Sendon JL, Remme WJ, et al. Effect of carvedilol in patients with or without renal impairment after myocardial infarction:analysis of the carvedilol post‐infarct survival control in left ventricular dysfunction (CAPRICORN) study. European Heart Journal 2010;31:571.
Choi 2001 {published data only}
    1. Choi JY, Lee KH, Hong KP, Kim BT, Seo JD, Lee WR, et al. Iodine‐123 MIBG imaging before treatment of heart failure with carvedilol to predict improvement of left ventricular function and exercise capacity. Journal of Nuclear Cardiology 2001;8(1):4‐9. - PubMed
Cicoira 2002 {published data only}
    1. Cicoira M, Rossi A, Bonapace S, Zanolla L, Perrot A, Francis A, et al. Effects of ACE gene insertion/deletion polymorphism on response to spironolactone in patients with chronic heart failure. American Journal of Medicine 2004;116(10):657‐61. - PubMed
    1. Cicoira M, Zanolla L, Rossi A, Golia G, Franceschini L, Brighetti G, et al. Long‐term, dose‐dependent effects of spironolactone on left ventricular function and exercise tolerance in patients with chronic heart failure. Journal of the American College of Cardiology 2002;40(2):304‐10. - PubMed
Cleland 1984 {published data only}
    1. Cleland JG, Dargie HJ, Hodsman GP, Ball SG, Robertson JI, Morton JJ, et al. Captopril in heart failure. A double blind controlled trial. British Heart Journal 1984;52(5):530‐5. - PMC - PubMed
Cleland 1999 {published data only}
    1. Cleland JG, Pennel D, Ray S, Murray G, MacFarlane P, Cowley A, et al. The carvedilol hibernation reversible ischaemia trial; marker of success (CHRISTMAS). The CHRISTMAS Study Steering Committee and Investigators. European Journal of Heart failure 1999;1(2):191‐6. - PubMed
Cleland 2001 {published data only}
    1. Cleland JG. ACE inhibitors for 'diastolic' heart failure? reasons not to jump to premature conclusions about the efficacy of ACE inhibitors among older patients with heart failure. European Journal of Heart Failure 2001;3(6):637‐9. - PubMed
Cleland 2003 {published data only}
    1. Cleland JG, Pennell DJ, Ray SG, Coats AJ, Macfarlane PW, Murray GD, et al. Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial. Lancet 2003;362(9377):14‐21. - PubMed
Cleland 2004 {published data only}
    1. Cleland JG, Huan Loh P, Freemantle N, Clark AL, Coletta AP. Clinical trials update from the European Society of Cardiology: SENIORS, ACES, PROVE‐IT, ACTION, and the HF‐ACTION trial. European Journal of Heart Failure 2004;6(6):787‐91. - PubMed
Cleland 2006 {published data only}
    1. Cleland JG, Coletta AP, Clark AL. Clinical trials update from the joint European Society and World Congress of Cardiology meeting: PEP‐CHF, ACCLAIM and the HHH study. European Journal of Heart Failure 2006;8(6):658‐61. - PubMed
Cleland 2007 {published data only}
    1. Cleland JGF, Coletta AP, Clark AL. Clinical trials update from the American College of Cardiology 2007: ALPHA, EVEREST, FUSION II, VALIDD, PARR‐2, REMODEL, SPICE, COURAGE, COACH, REMADHE, pro‐BNP for the evaluation of dyspnoea and THIS‐diet. European Journal of Heart Failure 2007;9(6‐7):740‐5. - PubMed
Cleland 2010 {published data only}
    1. Cleland JG, Coletta AP, Freemantle N, Ahmed D, Rubis P, Clark AL. Clinical trials update from the American Heart Association meeting 2009: HEAAL, FAIR‐HF, J‐CHF, HeartMate II, PACE and a meta‐analysis of dose‐ranging studies of beta‐blockers in heart failure. European Journal of Heart Failure 2010;12(2):197‐201. - PubMed
Cleland 2011 {published data only}
    1. Cleland JGF, Coletta AP, Cullington D, Castiello T, Boer RA, Clark AL. Clinical trials update from the European Society of Cardiology Meeting 2011: ARISTOTLE, SMART‐AV: QLV substudy, SHIFT: Echocardiography and quality of life substudies, European CRT Survey, and Basic Science Update. European Journal of Heart Failure 2011;13(12):1376‐80. - PubMed
Cleland 2013 {published data only}
    1. Cleland JG, Clark AL, Costanzo P, Francis DP. Diabetes, aliskiren, and heart failure: Let's bring ASTRONAUT down to earth. European Heart Journal 2013;34(40):3097‐9. - PubMed
Cohen‐Solal 2005 {published data only}
    1. Cohen‐Solal A, Rouzet F, Berdeaux A, Guludec D, Abergel E, Syrota A, et al. Effects of carvedilol on myocardial sympathetic innervation in patients with chronic heart failure. Journal of Nuclear Medicine 2005;46(11):1796‐803. - PubMed
Cohn 1993 {published data only}
    1. Cohn JN. ACE inhibitors. Cardiovascular Drugs and Therapy 1993;7(3):379. - PubMed
Cohn 1996a {published data only}
    1. Cohn JN. Slowing the progression of heart failure. European Heart Journal 1996;17(11):1609‐11. - PubMed
Cohn 1996b {published data only}
    1. Cohn JN. The management of chronic heart failure. New England Journal of Medicine 1996;335(7):490‐8. - PubMed
Cohn 2007 {published data only}
    1. Cohn JN. Myocardial structural effects of aldosterone receptor antagonism in heart failure. JACC 2007;50(7):597‐9. - PubMed
Coletta 2008 {published data only}
    1. Coletta AP, Cullington D, Clark AL, Cleland JGF. Clinical trials update from European Society of Cardiology meeting 2008: TIME‐CHF, BACH, BEAUTIFUL, GISSI‐HF, and HOME‐HF. European Journal of Heart Failure 2008;10(12):1264‐7. - PubMed
Coletta 2009 {published data only}
    1. Coletta AP, Clark AL, Cleland JG. Clinical trials update from the Heart Failure Society of America and the American Heart Association meetings in 2008: SADHART‐CHF, COMPARE, MOMENTUM, thyroid hormone analogue study, HF‐ACTION, I‐PRESERVE, beta‐interferon study, BACH, and ATHENA. European Journal of Heart Failure 2009;11(2):214‐9. - PMC - PubMed
Comin‐Colet 2002 {published data only}
    1. Comin‐Colet J, Sanchez‐Corral MA, Manito N, Gomez‐Hospital JA, Roca J, Fernandez‐Nofrerias E, et al. Effect of carvedilol therapy on functional mitral regurgitation, ventricular remodeling, and contractility in patients with heart failure due to left ventricular systolic dysfunction. Transplantation Proceedings 2002;34(1):177‐8. - PubMed
CONSENSUS {published data only}
    1. Eriksson SV, Caidahl K, Hall C, Eneroth P, Kjekshus J, Offstad J, et al. Atrial natriuretic peptide ANP(1‐98) and ANP(99‐126) in patients with severe chronic congestive heart failure: relation to echocardiographic measurements. A subgroup analysis from the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). Journal of Cardiac Failure 1995;1(2):109‐16. - PubMed
    1. Ljungman S, Kjekshus J, Swedberg K. Renal function in severe congestive heart failure during treatment with enalapril (the Cooperative North Scandinavian Enalapril Survival Study Trial). American Journal of Cardiology 1992;70(4):479‐87. - PubMed
    1. Swedberg K, Kjekshus J, CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). American Journal of Cardiology 1988;62(2):60A‐66A. - PubMed
    1. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). New England Journal of Medicine 1987;316(23):1429‐35. - PubMed
CONSENSUS II {published data only}
    1. Edner M, Bonarjee VV, Nilsen DW, Berning J, Carstensen S, Caidahl K. Effect of enalapril initiated early after acute myocardial infarction on heart failure parameters, with reference to clinical class and echocardiographic determinants. CONSENSUS II Multi‐Echo Study Group. Clinical Cardiology 1996;19(7):543‐8. - PubMed
Conti 2005 {published data only}
    1. Conti CR. Management of heart failure and left ventricular systolic dysfunction following acute myocardial infarction. Clinical Cardiology 2005;28(1):1‐2. - PMC - PubMed
Corder 1993 {published data only}
    1. Corder CN, Rubler S, Deere LF, Puls A, Peguero‐Rivera A, Nagarajan R, et al. Effect of cilazapril on exercise tolerance in congestive heart failure. Pharmacology 1993;46(3):148‐54. - PubMed
Crouse 2011 {published data only}
    1. Crouse M, Flack D, Kerns JW, Martin L, Pham D, Sudireddy R, et al. Clinical inquiries. Which medications benefit patients with diastolic heart failure?. Journal of Family Practice 2011;60(2):101‐2, 108. - PubMed
Dahlstrom 2007 {published data only}
    1. Dahlstrom U, Boman K, Brodin L A, Hagerman I, Willenheimer R. Treatment of heart failure and preserved systolic function. Lakartidningen 2007;104(34):2348‐50. - PubMed
Davie 2001 {published data only}
    1. Davie AP, Rumley A, Lowe GD, McMurray JJ. Effect of chronic angiotensin II type I receptor antagonism and angiotensin converting enzyme inhibition on plasma fibrinolytic variables in patients with heart failure. Thrombosis and Haemostasis 2001;86(6):1585‐6. - PubMed
DeBock 1994 {published data only}
    1. DeBock V, Mets T, Romagnoli M, Derde MP. Captopril treatment of chronic heart failure in the very old. Journal of Gerontology 1994;49(3):M148‐52. - PubMed
Dekleva 2012 {published data only}
    1. Dekleva M, Dungen HD, Gelbrich G, Incrot S, Suzic Lazic J, Pavlovic Kleut M, et al. Beta blockers therapy is associated with improved left ventricular systolic function and sustained exercise capacity in elderly patients with heart failure. CIBIS‐ELD sub‐study. Aging Clinical and Experimental Research 2012;24(6):675‐81. - PubMed
De Melo 2011 {published data only}
    1. Melo D, Barretto AC, Ramires JF. The impact of the rapid use of beta‐blockers on ventricular remodeling and mortality in end‐stage heart failure. JACC 2011;57(14):E259.
Demers 2001 {published data only}
    1. Demers C, McKelvie RS, Negassa A, Yusuf S, Investigators Resolvd Pilot Study. Reliability, validity, and responsiveness of the six‐minute walk test in patients with heart failure. American Heart Journal 2001;142(4):698‐703. - PubMed
Desai 2013 {published data only}
    1. Desai AS. Heart failure with preserved ejection fraction: Time for a new approach?. JACC 2013;62(4):272‐4. - PubMed
Deswal 2010 {published data only}
    1. Deswal A, Richardson P, Bozkurt B, Mann DL. Randomized trial of aldosterone antagonism in diastolic heart failure (RAAM‐DHF). Journal of Cardiac Failure 2010;16(8):S7. - PubMed
de Teresa 1995 {published data only}
    1. Teresa E, Espinosa JS, Gomez Doblas JJ. Cardiovascular pharmacology (IX). Angiotensin‐converting enzyme inhibitors in hypertension and heart failure. Revista Espanola de Cardiologia 1995;48(2):128‐41. - PubMed
Ding 2008 {published data only}
    1. Ding P, Li L, Xu ZY, Han L, He B, Hu Y. Ramipril in combination with irbesartan for treatment of chronic heart failure in patients with rheumatic heart disease. Academic Journal of Second Military Medical University 2008;29(6):675‐8.
Ditiatkov 1999 {published data only}
    1. Ditiatkov AE, Radzevich AE, Tikhonov VA, Gal IG. Ramipril treatment of heart failure in disseminated forms of pulmonary tuberculosis. Problemy Tuberkuleza 1999;2:31‐2. - PubMed
Donal 2008 {published data only}
    1. Donal E. Heart failure with preserved ejection fraction. La Revue de Médecine Interne 2008;29(Suppl 1):6‐7. - PubMed
Dragana 2015 {published data only}
    1. Dragana Stanojevic D, Apostolovic S, Salinger‐Martinovic S, Djordjevic‐Radojkovic D, Jankovic‐Tomasevic R, Pavlovic M, et al. Beta blockers in heart failure with preserved left ventricle ejection fraction. European Journal of Heart Failure 2015;17:364.
Edner 2013 {published data only}
    1. Edner M, Lund LH. Renin‐angiotensin system antagonists associated with reduced [corrected] mortality in diastolic heart failure. Lakartidningen 2013;110(7):331. - PubMed
Eichhorn 1994 {published data only}
    1. Eichhorn EJ, Hatfield B, Marcoux L, Risser RC. Functional importance of myocardial relaxation in patients with congestive heart failure. Journal of Cardiac Failure 1994;1(1):45‐56. - PubMed
Eichhorn 2003 {published data only}
    1. Eichhorn EJ, Grayburn PA, Mayer SA, John Sutton M, Appleton C, Plehn J, et al. Myocardial contractile reserve by dobutamine stress echocardiography predicts improvement in ejection fraction with beta‐blockade in patients with heart failure: the Beta‐Blocker Evaluation of Survival Trial (BEST). Circulation 2003;108(19):2336‐41. - PubMed
Er 2005 {published data only}
    1. Er F, Hoppe UC. Ivabradine ‐‐ a novel approach for heart rate lowering. Deutsche Medizinische Wochenschrift 2005;130(24):1501‐2. - PubMed
Ertl 1999 {published data only}
    1. Ertl G, Hu K. Left ventricular remodelling during treatment with beta‐blockers. Journal of Cardiovascular Risk 1999;6(3):145‐50. - PubMed
EudraCT 2004‐004169‐13 {published data only}
    1. EudraCT 2004‐004169‐13. A Pilot study to assess the effects of beta‐blockade on exercise capacity and BNP levels in patients with predominantly diastolic heart failure. www.clinicaltrialsregister.eu/ctr‐search/search?query=eudract_number:200... (first received 21 April 2005).
Fauchier 2009 {published data only}
    1. Fauchier L, Grimard C, Pierre B, Nonin E, Gorin L, Rauzy B, et al. Comparison of beta blocker and digoxin alone and in combination for management of patients with atrial fibrillation and heart failure. American Journal of Cardiology 2009;103(2):248‐54. - PubMed
Feola 2003 {published data only}
    1. Feola M, Menardi E, Ribichini F, Vado A, Deorsola A, Ferrero V, et al. Effects of the addition of a low dose of spironolactone on brain natriuretic peptide plasma level and cardiopulmonary function in patients with moderate congestive heart failure. Medical Science Monitor 2003;9(8):CR341‐5. - PubMed
Flammer 2013 {published data only}
    1. Flammer A, Sudano I, Enseleit F, Luscher TF, Noll G, Ruschitzka F. Mineralocorticoid receptor antagonism in patients with coronary artery disease and preserved ejection fraction‐a randomized, double‐blind trial. European Journal of Heart Failure 2013;12:S222‐3.
Flather 2016 {published data only}
    1. Flather MD, Gollop ND. Understanding mechanisms of action of beta‐blockers in heart failure with reduced and preserved ejection fraction. JACC Heart Failure 2016;4(2):150‐1. - PubMed
Flesch 2006 {published data only}
    1. Flesch M. Combined administration of AT1‐receptor antagonists and beta‐blockers in patients with chronic heart insufficiency. Internistische Praxis 2006;46(4):829‐32.
Follath 1996 {published data only}
    1. Follath F. Beta‐blockers in cardiac insufficiency. Time to reconsider?. Schweizer Medizinische Wochenschrift 1996;126(18):747‐9. - PubMed
Fonarow 2004 {published data only}
    1. Fonarow G, Cannon C, Epstein A. Questions and answers. Journal of Invasive Cardiology 2004;16 Suppl E:16E‐7E. - PubMed
Fonarow 2007 {published data only}
    1. Fonarow GC, Lukas MA, Robertson M, Colucci WS, Dargie HJ. Effects of carvedilol early after myocardial infarction: analysis of the first 30 days in Carvedilol Post‐Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN). American Heart Journal 2007;154(4):637‐44. - PubMed
Fowler 1999 {published data only}
    1. Fowler MB. The influence of beta‐adrenergic blocking drugs on morbidity and mortality in heart failure. Journal of Cardiovascular Risk 1999;6(3):141‐4. - PubMed
Franciosa 2002 {published data only}
    1. Franciosa JA, Taylor AL, Cohn JN, Yancy CW, Ziesche S, Olukotun A, et al. African‐American Heart Failure Trial (A‐HeFT): rationale, design, and methodology. Journal of Cardiac Failure 2002;8(3):128‐35. - PubMed
Fukunami 1991 {published data only}
    1. Fukunami M, Hashimura K, Ohmori M, Ikeda T, Umemoto K, Kumagai K, et al. Effectiveness of long‐term beta‐blocker therapy for dilated cardiomyopathy‐‐echocardiographical follow‐up. Cardiovascular Drugs and Therapy 1991;5(2):463‐9. - PubMed
Galinier 2007 {published data only}
    1. Galinier M. Treatment of heart failure with preserved ejection fraction. Archives des Maladies du Coeur et des Vaisseaux ‐ Pratique 2007;158:17‐21.
Galloe 2006 {published data only}
    1. Galloe AM, Skagen K, Christensen NJ, Nielsen SL, Frandsen EK, Bie P, et al. Dosage dependent hormonal counter regulation to combination therapy in patients with left ventricular dysfunction. Journal of Clinical Pharmacology and Therapy 2006;31(2):139‐47. - PubMed
Gardner 2003 {published data only}
    1. Gardner RS, Martin W, Carter R, McDonagh TA. Importance of beta blockade in the treatment of advanced heart failure. Heart 2003;89(12):1442‐4. - PMC - PubMed
Gardner 2004 {published data only}
    1. Gardner RS, McDonagh TA. The treatment of chronic heart failure due to left ventricular systolic dysfunction. Clinical Medicine 2004;4(1):18‐22. - PMC - PubMed
Ghali 2002 {published data only}
    1. Ghali JK, Pina IL, Gottlieb SS, Deedwania PC, Wikstrand JC, Group Merit‐Hf Study. Metoprolol CR/XL in female patients with heart failure: analysis of the experience in Metoprolol Extended‐Release Randomized Intervention Trial in Heart Failure (MERIT‐HF). Circulation 2002;105(13):1585‐91. - PubMed
Gheorghiade 2009 {published data only}
    1. Gheorghiade M, Khan S, Blair JE, Harinstein ME, Krum H, Mukherjee R, et al. The effects of eplerenone on length of stay and total days of heart failure hospitalization after myocardial infarction in patients with left ventricular systolic dysfunction. American Heart Journal 2009;158(3):437‐43. - PubMed
Good 1994 {published data only}
    1. Good JM, Brady AJ, Noormohamed FH, Oakley CM, Cleland JG. Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition. Circulation 1994;90(1):220‐4. - PubMed
Goodfield 1999 {published data only}
    1. Goodfield NE, Newby DE, Ludlam CA, Flapan AD. Effects of acute angiotensin II type 1 receptor antagonism and angiotensin converting enzyme inhibition on plasma fibrinolytic parameters in patients with heart failure. Circulation 1999;99(23):2983‐5. - PubMed
Gottlieb 1996 {published data only}
    1. Gottlieb SS, Singh S, Munger M, Eichhorn EJ, Ilgenfritz J, Hanyok J. Hemodynamic effects of the class III antiarrhythmic drug, d‐sotalol, in patients with congestive heart failure. American Journal of Cardiology 1996;78(12):1411‐5. - PubMed
Grajek 2008 {published data only}
    1. Grajek S. Do angiotensin receptor blockers increased the risk of myocardial infarction? The landscape after ONTARGET study. Kardiologia Polska 2008;66(12):1313‐24. - PubMed
Greenberg 1996 {published data only}
    1. Greenberg BH, Quinones MA, Koilpillai C, Limacher M, Shindler D, Benedict C, et al. Left ventricular dysfunction: Effects of long‐term enalapril therapy on remodeling. Cardiology Review 1996;13(7):40‐6.
Gremmler 2000 {published data only}
    1. Gremmler B, Kunert M, Schleiting H, Ulbricht LJ. Improvement of cardiac output in patients with severe heart failure by use of ACE‐inhibitors combined with the AT1‐antagonist eprosartan. European Journal of Heart Failure 2000;2(2):183‐7. - PubMed
Groenning 2000 {published data only}
    1. Groenning BA, Nilsson JC, Sondergaard L, Fritz‐Hansen T, Larsson HB, Hildebrandt PR. Antiremodeling effects on the left ventricle during beta‐blockade with metoprolol in the treatment of chronic heart failure. Journal of the American College of Cardiology 2000;36(7):2072‐80. - PubMed
Groenning 2001 {published data only}
    1. Groenning BA, Nilsson JC, Sondergaard L. Antiremodeling effects on the left ventricle during beta‐blockage with metaprolol in the treatment of chronic heart failure. Congestive Heart Failure 2001;7(1):58. - PubMed
Groenning 2002 {published data only}
    1. Groenning BA, Nilsson JC, Hildebrandt PR, Kjaer A, Fritz‐Hansen T, Larsson HB, et al. Neurohumoral prediction of left‐ventricular morphologic response to beta‐blockade with metoprolol in chronic left‐ventricular systolic heart failure. European Journal of Heart Failure 2002;4(5):635‐46. - PubMed
Gruner 2007 {published data only}
    1. Gruner Svealv B, Tang M S, Waagstein F, Andersson B. Pronounced improvement in systolic and diastolic ventricular long axis function after treatment with metoprolol. European Journal of Heart Failure 2007;9(6‐7):678‐83. - PubMed
Guazzi 1998 {published data only}
    1. Guazzi M, Pontone G, Trevisi N, Lomanto M, Matturri M, Agostoni P. A failed improvement in pulmonary function and exercise capacity with carvedilol in congestive heart failure despite an excellent effect on left ventricular function. Cardiologia 1998;43(2):181‐7. - PubMed
Guazzi 1999 {published data only}
    1. Guazzi M, Agostoni P, Matturri M, Pontone G, Guazzi M D. Pulmonary function, cardiac function, and exercise capacity in a follow‐up of patients with congestive heart failure treated with carvedilol. American Heart Journal 1999;138(3 Pt 1):460‐7. - PubMed
Gøtzsche 1992 {published data only}
    1. Gøtzsche CO, Søgaard P, Ravkilde J, Thygesen K. Effects of captopril on left ventricular systolic and diastolic function after acute myocardial infarction. American Journal of Cardiology 1992;70(2):156‐60. - PubMed
Hanping 1997 {published data only}
    1. Hanping Z, Guolong Y, Jing L, Jin H. The changes of PRA, ATII, ALD, ET and ANP in patients with left ventricular and intervention with enalapril. Bulletin of Hunan Medical University 1997;22(4):323‐6. - PubMed
Hara 2000 {published data only}
    1. Hara Y, Hamada M, Shigematsu Y, Suzuki M, Kodama K, Kuwahara T, et al. Effect of beta‐blocker on left ventricular function and natriuretic peptides in patients with chronic heart failure treated with angiotensin‐converting enzyme inhibitor. Circulation Journal – Official Journal of the Japanese Circulation Society 2000;64(5):365‐9. - PubMed
Hauf 1993 {published data only}
    1. Hauf GF, Roskamm H. Heart failure in coronary heart disease. Internist 1993;34(10):953‐60. - PubMed
Hole 2004 {published data only}
    1. Hole T, Frøland G, Gullestad L, Offstad J, Skjaerpe T. Metoprolol CR/XL improves systolic and diastolic left ventricular function in patients with chronic heart failure. Echocardiography 2004;21(3):215‐23. - PubMed
Holland 2010 {published data only}
    1. Holland DJ, Mottram PM, Hare JL, Jenkins C, Marwick TH. Extended duration of aldosterone blockade fails to improve diastolic dysfunction over the effects of blood pressure in patients with heart failure and normal ejection fraction. European Heart Journal 2010;31:731‐2.
Hong 2003 {published data only}
    1. Hong Y, Li Y, Wang XM, Liu XS, Li YN, Ouyang WM, et al. Effects of perindopril on plasma soluble TRAIL and receptor soluble DR5 in patients with congestive heart failure. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2003;19(4):366‐8. - PubMed
Hoppe 2007 {published data only}
    1. Hoppe UC. Treatment of heart failure with ACE inhibitors and beta‐blockers: what is next? AT1‐receptor antagonists?. Clinical Research in Cardiology 2007;96(4):196‐8. - PubMed
Hori 2004 {published data only}
    1. Hori M, Sasayama S, Kitabatake A, Toyo‐oka T, Handa S, Yokoyama M, et al. Low‐dose carvedilol improves left ventricular function and reduces cardiovascular hospitalization in Japanese patients with chronic heart failure: the Multicenter Carvedilol Heart Failure Dose Assessment (MUCHA) trial. American Heart Journal 2004;147(2):324‐30. - PubMed
Hung 2010 {published data only}
    1. Hung CL, Verma A, Uno H, Shin SH, Bourgoun M, Hassanein AH, et al. Longitudinal and circumferential strain rate, left ventricular remodeling, and prognosis after myocardial infarction. Journal of the American College of Cardiology 2010;56(22):1812‐22. - PubMed
IRIS‐HF {published data only}
    1. ACTRN12609000789268. Non‐invasive cardiac imaging in the detection and assessment of subclinical diabetic heart disease [Non‐invasive cardiac imaging in the detection and assessment of subclinical diabetic heart disease in type 2 diabetes mellitus patients ‐ outcome of antifibrotic therapy with spironolactone]. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=308109 (date received 10 September 2009).
    1. Doehner W, Todorovic J, Kennecke C, Rauchhaus M, Sandek A, Lainscak M, et al. Improved insulin sensitivity by the angiotensin receptor antagonist irbesartan in patients with systolic heart failure: a randomized double‐blinded placebo‐controlled study. International Journal of Cardiology 2012;161(3):137‐42. - PubMed
    1. NCT00347087. Effect of irbesartan on insulin sensitivity in chronic heart failure [Effect of the angiotensin II receptor antagonist irbesartan on insulin sensitivity and metabolic profile in patients with chronic heart failure]. clinicaltrials.gov/ct2/show/NCT00347087 (first received 4 July 2006).
Ito 2012 {published data only}
    1. Ito H, Ishii K, Kihara H, Kasayuki N, Nakamura F, Shimada K, et al. Adding thiazide to a renin‐angiotensin blocker improves left ventricular relaxation and improves heart failure in patients with hypertension. Hypertension Research 2012;35(1):93‐9. - PMC - PubMed
Jamieson 1991 {published data only}
    1. Jamieson MJ, Webster J, Fowler G, Rawles J, Smith FW, Petrie JC. A comparison of the chronic effect of oral xamoterol and enalapril on blood pressure and renal function in mild to moderate heart failure. British Journal of Clinical Pharmacology 1991;31(3):305‐12. - PMC - PubMed
Jellis 2014 {published data only}
    1. Jellis CL, Sacre JW, Wright J, Jenkins C, Haluska B, Jeffriess L, et al. Biomarker and imaging responses to spironolactone in subclinical diabetic cardiomyopathy. European Heart Journal 2014;15:776‐86. - PubMed
    1. Jellis CL, Wright J, Sacre J, Kennedy D, Jeffriess L, Fenwick J, et al. Backscatter, T1 mapping or pro‐collagen biomarkers for non‐invasive assessment of treatment response to anti‐fibrotic therapy in subclinical diabetic cardiomyopathy? A randomized trial. Journal of the American College of Cardiology 2012;59(13):E1076.
Jessup 2003 {published data only}
    1. Jessup M. Aldosterone blockade and heart failure. New England Journal of Medicine 2003;348(14):1380‐2. - PubMed
Jong 2010 {published data only}
    1. Jong P, McKelvie R, Yusuf S. Should treatment for heart failure with preserved ejection fraction differ from that for heart failure with reduced ejection fraction?. BMJ 2010;341:c4202. - PubMed
Kanoupakis 2008 {published data only}
    1. Kanoupakis EM, Manios EG, Mavrakis HE, Kallergis EM, Lyrarakis GM, Koutalas EP, et al. Electrophysiological effects of carvedilol administration in patients with dilated cardiomyopathy. Cardiovascular Drugs and Therapy 2008;22(3):169‐76. - PubMed
Kapel'ko 2011 {published data only}
    1. Kapel'ko VI. Diastolic dysfunction. Kardiologiia 2011;51(1):79‐90. - PubMed
Kasama 2007 {published data only}
    1. Kasama S, Toyama T, Sumino H, Matsumoto N, Sato Y, Kumakura H, et al. Additive effects of spironolactone and candesartan on cardiac sympathetic nerve activity and left ventricular remodeling in patients with congestive heart failure. Journal of Nuclear Medicine 2007;48(12):1993‐2000. - PubMed
Keren 1992 {published data only}
    1. Keren G, Pardes A, Eschar Y, Hansch E, Scherez J, Laniado S. Left ventricular filling dynamics by Doppler echocardiography in dilated cardiomyopathy: one‐year follow‐up in patients treated with captopril compared to placebo. Cardiology 1992;81(4‐5):196‐206. - PubMed
Keren 1994 {published data only}
    1. Keren G, Pardes A, Eschar Y, Koifman B, Scherez J, Geleranter I, et al. One‐year clinical and echocardiographic follow‐up of patients with congestive cardiomyopathy treated with captopril compared to placebo. Israel Journal of Medical Sciences 1994;30(1):90‐8. - PubMed
Khalid 2013 {published data only}
    1. Khalid U, Deswal A. Lack of definitive evidence for the use of renin‐angiotensin system antagonists for heart failure with preserved ejection fraction. Evidence Based Medicine 2013;18(6):226‐7. - PubMed
Khand 2015 {published data only}
    1. Khand AU, Chew PG, Douglas H, Jones J, Jan A, Cleland JG. The effect of carvedilol on B‐type natriuretic peptide and cardiac function in patients with heart failure and persistent atrial fibrillation. Cardiology 2015;130(3):153‐8. - PubMed
Kikuchi 2016 {published data only}
    1. Kikuchi N, Jujo K, Yamaguchi J, Ogawa H, Hagiwara N. Impact of left ventricular ejection function on blood pressure‐lower ing therapy in hypertensive patients with coronary artery disease. Journal of Hypertension 2016;34(5):1011‐8. - PubMed
Kimura 2011 {published data only}
    1. Kimura M, Ogawa H, Wakeyama T, Takaki A, Iwami T, Hadano Y, et al. Effects of mineralocorticoid receptor antagonist spironolactone on atrial conduction and remodeling in patients with heart failure. Journal of Cardiology 2011;57(2):208‐14. - PubMed
Kinugawa 2007 {published data only}
    1. Kinugawa S. Diabetic heart disease. Nippon Rinsho 2007;65(Suppl 5):465‐9. - PubMed
Kjekshus 2007 {published data only}
    1. Kjekshus J. Prescription of beta‐blockers in patients with advanced heart failure and preserved left ventricular ejection fraction. Clinical implications and survival. European Journal of Heart Failure 2007;9(9):962; author reply 962‐3. - PubMed
Kjøller‐Hansen 1998 {published data only}
    1. Kjøller‐Hansen L, Steffensen R, Grande P. The Angiotensin Converting Enzyme Inhibition Post Revascularization Study (APRES). Effects of ramipril in patients with reduced left ventricular function. Rationale, design, methods, baseline characteristics and first‐year experience. Scandinavian Cardiovascular Journal 1998;32(4):225‐32. - PubMed
Kleber 1991a {published data only}
    1. Kleber FX, Doering W. Prognosis of mild chronic heart failure: effects of the ACE inhibitor captopril [Prognose bei leichter chronischer Herzinsuffizienz: Einflüsse des ACE‐Hemmers Captopril]. Herz 1991;16(Spec No 1):283‐93. - PubMed
Kleber 1991b {published data only}
    1. Kleber FX, Nussberger J, Niemoller L, Doering W, Brunner H. Development of heart failure after myocardial infarct: changes in plasma renin activity, angiotensin II, catecholamines and atrial natriuretic peptide [Entwicklung der Herzinsuffizienz nach Myokardinfarkt: Veränderungen von Plasma‐Reninaktivität, Angiotensin II, Katecholaminen und atrialem natriuretischen Peptid]. Zeitschrift für Kardiologie 1991;80(Suppl 8):111‐2. - PubMed
Kongstad‐Rasmussen 1998 {published data only}
    1. Kongstad‐Rasmussen O, Blomstrand M, Dahlstrom U, Wranne B. Treatment with ramipril improves systolic function even in patients with mild systolic dysfunction and symptoms of heart failure after acute myocardial infarction. Clinical Cardiology 1998;21(11):807‐11. - PMC - PubMed
Krum 1996 {published data only}
    1. Krum H, Gu A, Wilshire‐Clement M, Sackner‐Bernstein J, Goldsmith R, Medina N, et al. Changes in plasma endothelin‐1 levels reflect clinical response to beta‐blockade in chronic heart failure. American Heart Journal 1996;131(2):337‐41. - PubMed
Krum 2015 {published data only}
    1. Krum H, McMurray JJ, Abraham WT, Dickstein K, Kober L, Desai AS, et al. The Aliskiren Trial to Minimize OutcomeS in Patients with HEart failure trial (ATMOSPHERE): revised statistical analysis plan and baseline characteristics. European Journal of Heart Failure 2015;17(10):1075‐83. - PubMed
Kulbertus 2003 {published data only}
    1. Kulbertus H. Clinical study of the month. The CHARM study. Revue Medicale de Liege 2003;58(10):646‐52. - PubMed
Kuznar 2003 {published data only}
    1. Kuznar W. Blocking aldosterone reduces deaths in post‐MI heart failure. Cardiology Review 2003;20(6):1+14.
Lang 1995 {published data only}
    1. Lang CC, McAlpine HM, Kennedy N, Rahman AR, Lipworth BJ, Struthers AD. Effects of lisinopril on congestive heart failure in normotensive patients with diastolic dysfunction but intact systolic function. European Journal of Clinical Pharmacology 1995;49(1‐2):15‐9. - PubMed
Larsen 1996 {published data only}
    1. Larsen J, Sykulski R, Jensen G, Dossegger L, Trimarco B, Moccetti T, et al. Adaptive changes in the acute haemodynamic effects of cilazapril during chronic treatment. Comparison with long‐term clinical effect. European Journal of Clinical Pharmacology 1996;50(6):433‐41. - PubMed
Lechat 1993 {published data only}
    1. Bounhoure JP. Perindopril and chronic cardia failure. Archives des Maladies du Coeur et des Vaisseaux 1991;84(Spec Iss IV):89‐92. - PubMed
    1. Bounhoure JP, Bottineau G, Lechat P, Garnham J, Lapeyre G. Contribution of perindopril to the treatment of chronic congestive cardiac insufficiency. Multicenter pilot double blind study versus placebo. Archives des Maladies du Coeur et des Vaisseaux 1989;82(Spec No 1):73‐8. - PubMed
    1. Bounhoure JP, Bottineau G, Lechat P, Garnham J, Lapeyre G. Value of perindopril in the treatment of chronic congestive heart failure. Multicenter double‐blind placebo‐controlled study. Clinical and experimental hypertension. Part A, Theory and practice 1989;11(Suppl 2):575‐86. - PubMed
    1. Lechat P, Garnham SP, Desche P, Bounhoure JP. Efficacy and acceptability of perindopril in mild to moderate chronic congestive heart failure. American Heart Journal 1993;126(3 II Suppl):798‐806. - PubMed
Leonetti 1999 {published data only}
    1. Leonetti Luparini R, Celli V, Piccirillo G, Guidi V, Cacciafesta M, Marigliano V. Carvedilol in elderly patients with chronic heart failure, a 12 weeks randomized, placebo controlled open trial. Archives of Gerontology and Geriatrics 1999;29(3):275‐82. - PubMed
Lewis 1988 {published data only}
    1. Lewis GR. Lisinopril versus placebo in older congestive heart failure patients. American Journal of Medicine 1988;85(3B):48‐54. - PubMed
Li 2005 {published data only}
    1. Li ZK, Mei X, Zhu SJ, Wang J, Tian Y, Zhou YZ, et al. Ventricular remodeling and cardiovascular events in patients with chronic heart failure and the interventional effects of metoprolol. Chinese Journal of Clinical Rehabilitation 2005;9(35):28‐30.
Liebson 2004 {published data only}
    1. Liebson PR. VALIANT and EUROPA. Preventive Cardiology 2004;7(1):42‐4. - PubMed
Lindenfeld 2001 {published data only}
    1. Lindenfeld J, Robertson AD, Lowes BD, Bristow MR, Investigators Mocha. Aspirin impairs reverse myocardial remodeling in patients with heart failure treated with beta‐blockers. JACC 2001;38(7):1950‐6. - PubMed
Lindsay 1999 {published data only}
    1. Lindsay J, Freemantle N, Nazareth I. Beta‐blockers in heart failure. Lancet 1999;353(9157):1011‐2. - PubMed
Liu 2014 {published data only}
    1. Liu X, Zhong C, Zhao P, Zhang Z, Jia N, Su S, et al. Analysis of therapeutic effect and safety of target‐dose metoprolol in the treatment of patients with diabetes mellitus with chronic heart failure. Pakistan Journal of Medical Sciences 2014;30(1):7‐11. - PMC - PubMed
Logeart 2006 {published data only}
    1. Logeart D. Diastolic heart failure. Archives des Maladies du Coeur et des Vaisseaux ‐ Pratique 2006;147:23‐7. - PubMed
Lopez 2000 {published data only}
    1. Lopez Herrero F, Pardo Alvarez J. Spironolactone in heart failure. Atención Primaria 2000;25(4):281. - PMC - PubMed
Lou 2009 {published data only}
    1. Lou YF, Shi XP, Tong H, Yu GY, Yao GD, Dong K. Re: Effect of carvedilol on plasma adiponectin concentration in patients with chronic heart failure. Circulation Journal 2009;73(12):2363; author reply 2364. - PubMed
Luo 2007 {published data only}
    1. Luo M, Bi Y, Xu YX. Effects of metoprolol on beta1 adrenergic receptor polymorphism and receptor density in urban Chinese patients with heart failure. Chinese Medical Journal 2007;120(19):1720‐3. - PubMed
Ma 2005 {published data only}
    1. Ma HY. Effect of valsartan and hydrochloric benazepril on ventricular remodeling and cardiac function of patients with heart failure. Journal of Clinical Rehabilitative Tissue Engineering Research 2005;9(47):22‐4.
MacGregor 2009 {published data only}
    1. MacGregor JF, Wachter SB, Munger M, Stoddard G, Bristow MR, Gilbert EM. Carvedilol produces sustained long‐term benefits: follow‐up at 12 years. Congestive Heart Failure 2009;15(1):5‐8. - PubMed
Mak 2008 {published data only}
    1. Mak G, Murphy NM, Phelan D, Watson C, O'Loughlin C, Baugh J, et al. The effects of low dose eplerenone on markers of collagen turnover in diastolic heart failure. Irish Journal of Medical Science 2008;177(Suppl 12):S398.
Malnick 2007 {published data only}
    1. Malnick SD, Somin M. The VALIDD study. Lancet 2007;370(9591):931. - PubMed
Maron 2013 {published data only}
    1. Maron M, Kerur B, Chan RH, McGraw AP, Qiao X, Paruchuri V, et al. Can spironolactone mitigate myocardial fibrosis and alter sudden death risk and heart failure symptoms in patients with hypertrophic cardiomyopathy? A prospective, randomized trial. Circulation 2013;128(22):A16910.
Mazayev 1998 {published data only}
    1. Mazayev VP, Fomina IG, Kazakow EN, Sulimov VA, Zvereva TV, Lyusov VA, et al. Valsartan in heart failure patients previously untreated with an ACE inhibitor. International Journal of Cardiology 1998;65(3):239‐46. - PubMed
McAnulty 2004 {published data only}
    1. McAnulty JH Jr. Valsartan, captopril, or both in myocardial infarction. New England Journal of Medicine 2004;350(9):943‐5; author reply 943. - PubMed
McCullough 2012 {published data only}
    1. McCullough PA, Cowan S. Mineralocorticoid receptor antagonists and mortality in heart failure with concurrent atrial fibrillation. Circulation 2012;5(5):550‐1. - PubMed
McIlwain 1997 {published data only}
    1. McIlwain JS. HCQIP Project Report‐‐findings released in Use of Ace Inhibitors in Heart Failure Project. Journal of the Mississippi State Medical Association 1997;38(7):282. - PubMed
McKelvie 2012 {published data only}
    1. McKelvie RS. Heart failure. American Family Physician 2012;86(2):182‐4. - PubMed
McMurray 2000 {published data only}
    1. McMurray J. AT(1) receptor antagonists‐beyond blood pressure control: possible place in heart failure treatment. Heart 2000;84 Suppl 1:i42‐5: discussion i50. - PMC - PubMed
McMurray 2004 {published data only}
    1. McMurray JJ, Pfeffer MA, Swedberg K, Dzau VJ. Which inhibitor of the renin‐angiotensin system should be used in chronic heart failure and acute myocardial infarction?. Circulation 2004;110(20):3281‐8. - PubMed
Melo 2011 {published data only}
    1. Melo DSB, Barretto ACP, Oliveira AI, Uchida AH, Ochiai ME, Cardoso JN, et al. The impact of the rapid use of beta blockers on ventricular mortality and remodeling in and‐stage heart failure. European Journal of Heart Failure. Supplement 2011;10:S173.
Melo 2012 {published data only}
    1. Melo DB, Barretto AP, Ochiai M, Cardoso J, Oliveira A, Melo F, et al. The impact of the rapid use of beta‐blockers on ventricular remodeling and mortality in end‐stage heart failure (the FAST study). Circulation 2012;125(19):e754.
Messias 2016 {published data only}
    1. Messias L R, Ferreira A G, Miranda S M, Teixeira J A, Azevedo J C, Messias A C, et al. Effect of Nebivolol on MIBG Parameters and Exercise in Heart Failure with Normal Ejection Fraction. Arquivos Brasileiros de Cardiologia 2016;106(5):358‐66. - PMC - PubMed
Meuleman 2007 {published data only}
    1. Meuleman C. Diastolic dysfunction in heart failure with CHARMES (candesartan in heart failure assessment of reduction in mortality and morbidity) preserved systolic function: Results of the CHARM echocardiographic sub‐study. Medecine Therapeutique ‐ Cardio 2007;3(5):346‐9.
Mitrovic 2005 {published data only}
    1. Mitrovic V. Conclusions from CHARM interview with Prof. Veselin Mitrovich, Bad Nauheim. Strong evidence: more help for weak hearts. MMW Fortschritte der Medizin 2005;147(13):48‐9. - PubMed
Mochizuki 2004 {published data only}
    1. Mochizuki S, Shimizu M, Taniguchi I, Kanae K, Yoshida S, Tajima N, et al. JIKEI HEART Study‐‐a morbi‐mortality and remodeling study with valsartan in Japanese patients with hypertension and cardiovascular disease. Cardiovascular Drugs and Therapy 2004;18(4):305‐9. - PubMed
Morales 2011 {published data only}
    1. Morales H, Espinoza F, Larrea R, Gonzalez B, Puga L, Vukusich A, et al. A randomized, double‐blind, placebo‐controlled trial of spironolactone on diastolic dysfunction in diabetic patients. Diabetes 2011;60:A562.
Murdoch 2001 {published data only}
    1. Murdoch DR, McDonagh TA, Farmer R, Morton JJ, McMurray JJ, Dargie HJ. ADEPT: Addition of the AT1 receptor antagonist eprosartan to ACE inhibitor therapy in chronic heart failure trial: hemodynamic and neurohormonal effects. American Heart Journal 2001;141(5):800‐7. - PubMed
NCT00293150 {published data only}
    1. NCT00293150. Reversing endothelial and diastolic dysfunction and improving collagen turnover in diastolic heart failure (PREDICT). clinicaltrials.gov/show/NCT00293150 (first posted 17 February 2006).
NCT00523757 {published data only}
    1. NCT00523757. Aldosterone blockade in heart failure (ARCTIC‐D) [Aldosterone‐blockade randomized controlled trial In CHF ‐ diastolic]. clinicaltrials.gov/show/NCT00523757 (first received 31 August 2007).
NCT01691118 {published data only}
    1. NCT01691118. A trial of fimasartan for early diastolic heart failure (FINE) [Fimasartan for improvement of diastolic dysfunction in hypertensive patients]. clinicaltrials.gov/show/NCT01691118 (first posted 24 September 2012).
Nodari 2003 {published data only}
    1. Nodari S, Metra M, Dei Cas L. Beta‐blocker treatment of patients with diastolic heart failure and arterial hypertension. A prospective, randomized, comparison of the long‐term effects of atenolol vs. nebivolol. European Journal of Heart Failure 2003;5(5):621‐7. - PubMed
Nunez 2016 {published data only}
    1. Nunez J, Nunez E, Sanchis J. Spironolactone in patients with heart failure and preserved ejection fraction. Revista Clinica Espanola 2016;216(2):111. - PubMed
O'Callaghan 1995 {published data only}
    1. O'Callaghan PA, Walsh MJ. ACE inhibitors in the management and prevention of heart failure. Irish Medical Journal 1995;88(2):48,50. - PubMed
O'Keefe 2008 {published data only}
    1. O'Keefe JH, Abuissa H, Pitt B. Eplerenone improves prognosis in postmyocardial infarction diabetic patients with heart failure: results from EPHESUS. Diabetes Obesity and Metabolism 2008;10(6):492‐7. - PubMed
O'Keeffe 2015 {published data only}
    1. O'Keeffe St, Sharma N, Donnellan Ca, Lye M. Does stopping diuretics prevent first dose hypotension in older heart failure patients commencing ACE inhibitor therapy?. European Geriatric Medicine 2015; Vol. 6, issue 4:366‐7.
O'Meara 2012 {published data only}
    1. O'Meara E, Khairy P, Blanchet MC, Denus S, Pedersen OD, Levesque S, et al. Mineralocorticoid receptor antagonists and cardiovascular mortality in patients with atrial fibrillation and left ventricular dysfunction: insights from the Atrial Fibrillation and Congestive Heart Failure Trial. Circulation 2012;5(5):586‐93. - PubMed
Ostergren 2004 {published data only}
    1. Ostergren J. Candesartan for the treatment of hypertension and heart failure. Expert Opinion in Pharmacotherapy 2004;5(7):1589‐97. - PubMed
Palazzuoli 2005 {published data only}
    1. Palazzuoli A, Quatrini I, Vecchiato L, Calabria P, Gennari L, Martini G, et al. Left ventricular diastolic function improvement by carvedilol therapy in advanced heart failure. Journal of Cardiovascular Pharmacology 2005;45(6):563‐8. - PubMed
Paolisso 1992 {published data only}
    1. Paolisso G, Gambardella A, Marrazzo G, Verza M, Teasuro P, Varricchio M, et al. Metabolic and cardiovascular benefits deriving from beta‐adrenergic blockade in chronic congestive heart failure. American Heart Journal 1992;123(1):103‐10. - PubMed
Paraskevaidis 2006 {published data only}
    1. Paraskevaidis IA, Tsiapras D, Karavolias G, Adamopoulos S, Dodouras T, Cokkinos P, et al. The effect of carvedilol therapy on myocardial functional reserve in patients with advanced heart failure caused by nonischemic dilated cardiomyopathy. Journal of the American Society of Echocardiography 2006;19(5):529‐35. - PubMed
Park 2016 {published data only}
    1. Park K, Park TH. Comparative effects of nebivolol and carvedilol on left ventricular diastolic function in older heart failure patients with preserved ejection fraction: study protocol for a randomized controlled trial. Trials 2016;17(1):530. - PMC - PubMed
Patten 1997 {published data only}
    1. Patten RD, Kronenberg MW, Benedict CR, Udelson JE, Kinan D, Stewart D, et al. Acute and long‐term effects of the angiotensin‐converting enzyme inhibitor, enalapril, on adrenergic activity and sensitivity during exercise in patients with left ventricular systolic dysfunction. American Heart Journal 1997;134(1):37‐43. - PubMed
Pennell 2000 {published data only}
    1. Pennell DJ, Ray SG, Davies G, Burgess M, Webster J, Slomka P, et al. The carvedilol hibernation reversible ischaemia trial, marker of success (CHRISTMAS) study. Methodology of a randomised, placebo controlled, multicentre study of carvedilol in hibernation and heart failure. International Journal of Cardiology 2000;72(3):265‐74. - PubMed
Pierard 2002 {published data only}
    1. Pierard L. Clinical study of the month. Effects of valsartan in chronic heart failure: the VAL‐HeFT study. Revue Medical de Liege 2002;57(1):57‐9. - PubMed
Pina 2004 {published data only}
    1. Pina IL. Valsartan in acute myocardial infarction trial. Current Cardiology Reports 2004;6(3):159‐60. - PubMed
Pitt 2005 {published data only}
    1. Pitt B, White H, Nicolau J, Martinez F, Gheorghiade M, Aschermann M, et al. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. JACC 2005;46(3):425‐31. - PubMed
Pitt 2008 {published data only}
    1. Pitt B, Bakris G, Ruilope LM, DiCarlo L, Mukherjee R, Investigators Ephesus. Serum potassium and clinical outcomes in the Eplerenone Post‐Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Circulation 2008;118(16):1643‐50. - PubMed
Pitt 2011 {published data only}
    1. Pitt B, Latini R, Maggioni AP, Solomon SD, Smith BA, Wright M, et al. Neurohumoral effects of aliskiren in patients with symptomatic heart failure receiving a mineralocorticoid receptor antagonist: the Aliskiren Observation of Heart Failure Treatment study. European Journal of Heart Failure 2011;13(7):755‐64. - PubMed
Pourdjabbar 2015 {published data only}
    1. Pourdjabbar A, Dwivedi G, Haddad R, Saikali A, Mielniczuk L, Haddad H. Heart rate control in patients with left ventricular systolic dysfunction and heart failure. International Journal of Cardiology 2015;184:276‐7. - PubMed
Premkumar 2016 {published data only}
    1. Premkumar M, Rangegowda D, Shasthry SM, Vyas TS, Goyal R, Singh JK, et al. Targeted heart rate reduction using carvedilol ivabradine improves left ventricular diastolic dysfunction,clinical progression and survival in cirrhosis. Indian Journal of Gastroenterology 2016;35(1):A46‐7. - PubMed
Quaife 1998 {published data only}
    1. Quaife RA, Christian PE, Gilbert EM, Datz FL, Volkman K, Bristow MR. Effects of carvedilol on right ventricular function in chronic heart failure. American Journal of Cardiology 1998;81(2):247‐50. - PubMed
Ramaswamy 2003 {published data only}
    1. Ramaswamy K. Beta blockers improve outcome in patients with heart failure and atrial fibrillation: U.S. carvedilol study. Cardiac Electrophysiology Review 2003;7(3):229‐32. - PubMed
Remme 2001 {published data only}
    1. Remme WJ, Committee Carmen Steering, Investigators. The Carvedilol and ACE‐Inhibitor Remodelling Mild Heart Failure EvaluatioN trial (CARMEN)‐‐rationale and design. Cardiovascular Drugs and Therapy 2001;15(1):69‐77. - PubMed
Remme 2004 {published data only}
    1. Remme WJ, Riegger G, Hildebrandt P, Komajda M, Jaarsma W, Bobbio M, et al. The benefits of early combination treatment of carvedilol and an ACE‐inhibitor in mild heart failure and left ventricular systolic dysfunction. The carvedilol and ACE‐inhibitor remodelling mild heart failure evaluation trial (CARMEN). Cardiovascular Drugs and Therapy 2004;18(1):57‐66. - PubMed
Remme 2005 {published data only}
    1. Remme WJ. Could beta‐blockers precede or replace angiotensin‐converting enzyme inhibitors in heart failure?. Heart Failure Clinic 2005;1(1):67‐75. - PubMed
Rimatori 1990 {published data only}
    1. Rimatori C, Zayat M. Captopril in the early phase of cardiac failure: effects on left ventricular diastolic function. Journal of International Medicine Supplement 1990;228(733):58.
Roongsritong 2005 {published data only}
    1. Roongsritong C, Sutthiwan P, Bradley J, Simoni J, Power S, Meyerrose GE. Spironolactone improves diastolic function in the elderly. Clinical Cardiology 2005;28(10):484‐7. - PMC - PubMed
Rosa 2011 {published data only}
    1. Rosa MLD. Effect of aliskiren and antihypertensive drugs on diastolic function in hypertensives with diastolic dysfunction: A randomised study. Journal of Clinical Hypertension 2011;13(4):A81.
Rosenkranz 2003 {published data only}
    1. Rosenkranz S, Erdmann E. Hemodynamic effects of the beta blocker nebivolol. Internist 2003;44(4):481‐2. - PubMed
Rossignol 2011 {published data only}
    1. Rossignol P, Manard J, Fay R, Gustafsson F, Pitt B, Zannad F. Eplerenone survival benefits in heart failure patients post‐myocardial infarction are independent from its diuretic and potassium‐sparing effects: Insights from an EPHESUS (Eplerenone Post‐Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) substudy. JACC 2011;58(19):1958‐66. - PubMed
Sakai 2011 {published data only}
    1. Sakai H, Tsutamoto T, Kawahara C, Fujii M, Yamaji M, Ohnishi M, et al. Effects of aliskiren on Left ventricular remodeling in patients with dilated cardiomyopathy. European Heart Journal 2011;32:787.
Sanderson 1998 {published data only}
    1. Sanderson JE, Chan SKW, Yu CM, Yeung LYC, Chan WM, Raymond K, et al. Beta blockers in heart failure: a comparison of a vasodilating beta blocker with metoprolol. Heart 1998;79:86‐92. - PMC - PubMed
Sanghera 2011 {published data only}
    1. Sanghera KM. Keep patients with heart failure out of hospital: Ensure they get target doses. Pharmaceutical Journal 2011;286(7658):727‐8.
Santulli 2015 {published data only}
    1. Santulli G. beta‐Blockers in diabetic patients with heart failure. JAMA Internal Medicine 2015;175(4):657. - PubMed
Sardu 1991 {published data only}
    1. Sardu G. Treatment of mild‐to‐moderate congestive heart failure with the angiotensin converting enzyme inhibitor quinapril. Advances in Therapy 1991;8(3):124‐32.
Schindler 2008 {published data only}
    1. Schindler B. Angiotensin receptor antagonists: No advantage for hypertensive patients with diastolic dysfunction. Medizinische Monatsschrift fur Pharmazeuten 2008;31(5):195‐6. - PubMed
Schwab 2009 {published data only}
    1. Schwab J, Schneider M P, Pauschinger M, Schmieder R E. Hypertension and diastolic dysfunction. MMW Fortschritte der Medizin 2009;151(23):41‐3. - PubMed
Segovia 2008 {published data only}
    1. Segovia J, Bermejo J, Alfonso F. Summary of the clinical studies reported in the 57th Scientific Session of the American College of Cardiology (Chicago, USA, 30 march‐2 april 2008). Revista Espanola de Cardiologia 2008;61(7):726‐37. - PubMed
Shimamoto 2007 {published data only}
    1. Shimamoto K, Kawana M. The Carvedilol and ACE‐Inhibitor Remodelling Mild Heart Failure Evaluation Trial. Nippon Rinsho 2007;65 Suppl 4:531‐6. - PubMed
Sidorenko 2008 {published data only}
    1. Sidorenko BA, Bugrimova MA, Iosava IK, Pataraia SA, Preobrazhenskii DV. Controlled release metoprolol succinate in MERIT‐HF. Analysis of patients subgroups. Kardiologiia 2008;48(3):85‐8. - PubMed
Silva 2014 {published data only}
    1. Silva MC, Rassi CH, Meira ZM, Giannetti JG, Vainzof M, Zatz M, et al. Progression of myocardial fibrosis by magnetic resonance imaging in patients with duchenne and becker muscular dystrophy and preserved left ventricular ejection fraction‐a randomized clinical trial for treatment with ACE inhibitors. Journal of Cardiovascular Magnetic Resonance 2014;16:P311.
Smith 2012 {published data only}
    1. Smith JG, Kohl S, Kornhall B, Ekmehag B. Congestive heart failure, part 2: treatment. Lakartidningen 2012;109(41):1829‐34. - PubMed
Spoto 2002 {published data only}
    1. Spoto S, Palma Modoni A, Galasso L. Diastolic cardiac insufficiency. La Clinica Terapeutica 2002;153(5):355‐7. - PubMed
Stecker 2005 {published data only}
    1. Stecker EC, McAnulty JH. Letter regarding article by Weintraub et al, "Cost‐effectiveness of eplerenone compared with placebo in patients with myocardial infarction complicated by left ventricular dysfunction and heart failure". Circulation 2005;112(5):e74. - PubMed
Stiefelhagen 2006 {published data only}
    1. Stiefelhagen P. New study results in cardiology. Internist 2006;47(3):311‐6. - PubMed
Struthers 2004 {published data only}
    1. Struthers AD. Aldosterone in heart failure: pathophysiology and treatment. Current Heart Failure Reports 2004;1(4):171‐5. - PubMed
Swedberg 1996 {published data only}
    1. Swedberg K, Sharpe N. The value of angiotensin converting enzyme inhibitors for the treatment of patients with left ventricular dysfunction, heart failure or after acute myocardial infarction. European Heart Journal 1996;17(9):1306‐11. - PubMed
Swedberg 1999 {published data only}
    1. Swedberg K. Beta‐blockers and heart failure. Journal of Cardiovascular Risk 1999;6(3):129‐30. - PubMed
Szajnbok 1993 {published data only}
    1. Szajnbok FE, Barretto AC, Mady C, Parga Filho J, Gruppi C, Alfieri RG, et al. Beneficial effects of enalapril on the diastolic ventricular function in Chagas myocardiopathy. Arquivos Brasileiros de Cardiologia 1993;60(4):273‐8. - PubMed
Szymanski 2009 {published data only}
    1. Szymanski P, Klisiewicz A, Hoffman P. Therapeutic options for systemic right ventricular failure. Heart 2009;95(23):1950‐1; author reply 1951. - PubMed
Taheri 2009 {published data only}
    1. Taheri S, Mortazavi M, Shahidi S, Pourmoghadas A, Garakyaraghi M, Seirafian S, et al. Spironolactone in chronic hemodialysis patients improves cardiac function. Saudi Journal of Kidney Diseases and Transplantation 2009;20(3):392‐7. - PubMed
Takekoshi 2004 {published data only}
    1. Takekoshi N, Asaji T, Tada N. Hypertension in patients with heart failure. Nippon Rinsho 2004;62 Suppl 3:478‐83. - PubMed
Tala 2011a {published data only}
    1. Tala S, Rossignol P, Fay R, Pitt B, Zannad F. Relation of loop diuretic dose to morbimortality in patients with heart failure and left ventricular systolic dysfunction: Insights from EPHESUS. European Journal of Heart Failure. Supplement 2011;10:S114‐5.
Tala 2011b {published data only}
    1. Tala S, Rossignol P, Fay R, Pitt B, Zannad F. Relation of loop diuretic dose to morbimortality in patients with heart failure and left ventricular systolic dysfunction: Insights from the eplerenone post‐acute myocardial infarction heart failure efficacy and survival study (EPHESUS). Fundamental and Clinical Pharmacology 2011;25:2.
Tan 2013 {published data only}
    1. Tan LB, Schlosshan D, Hall AS. Cardiac functional benefits of ivabradine therapy in patients with severe heart failure. International Journal of Cardiology 2013;165(2):389‐90. - PubMed
Tatsumi 2006 {published data only}
    1. Tatsumi T, Matsubara H. Cardioprotective effect of aldosterone antagonists for ventricular remodeling. Nippon Rinsho 2006;64 Suppl 5:524‐9. - PubMed
Taylor 2003 {published data only}
    1. Taylor AL. The African‐American Heart Failure Trial (A‐HeFT): rationale and methodology.[Erratum appears in J Card Fail. 2003 Dec;9(6):481 Note: Dosage error in article text]. Journal of Cardiac Failure 2003;9(5 Suppl Nitric Oxide):S216‐9. - PubMed
Teerlink 2003 {published data only}
    1. Teerlink JR, Massie BM. Late breaking heart failure trials from the 2003 ACC meeting: EPHESUS and COMPANION. Journal of Cardiac Failure 2003;9(3):158‐63. - PubMed
Tereshchenko 2005 {published data only}
    1. Tereshchenko SN, Kositsyna IV, Dzhaiani NA, Golubev AV, Kochetov AG. The use of esmolol in patients with myocardial infarction complicated with acute left ventricular failure. Kardiologiia 2005;45(6):19‐22. - PubMed
Thornton 2004 {published data only}
    1. Thornton PL, Ahmed A. Angiotensin‐converting enzyme inhibitors, beta‐blockers, and mortality in systolic heart failure. JACC 2004;43(7):1333; author reply 1333‐4. - PubMed
Thune 2008 {published data only}
    1. Thune JJ, Signorovitch J, Kober L, Velazquez EJ, McMurray JJ, Califf RM, et al. Effect of antecedent hypertension and follow‐up blood pressure on outcomes after high‐risk myocardial infarction. Hypertension 2008;51(1):48‐54. - PubMed
Tinoco 2004 {published data only}
    1. Tinoco Mesquita E, Socrates J, Rassi S, Villacorta H, Mady C. Heart failure with preserved systolic function. Arquivos Brasileiros de Cardiologia 2004;82(5):494‐500. - PubMed
Tsutamoto 2000 {published data only}
    1. Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, et al. Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure. JACC 2000;36(3):838‐44. - PubMed
Tsutamoto 2001 {published data only}
    1. Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, et al. Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. Journal of the American College of Cardiology 2001;37(5):1228‐33. - PubMed
Tsutamoto 2005 {published data only}
    1. Tsutamoto T, Horie M, Hayashi M. Left ventricular remodeling post myocardial infarction. Nippon Rinsho 2005;63 Suppl 3:323‐9. - PubMed
Tumasyan 2010 {published data only}
    1. Tumasyan LR, Adamyan KG. Comparative efficacy of combined therapy with angiotensin converting enzyme inhibitor and angiotensin receptor blocker and direct renin inhibitor in patients with severe chronic heart failure. European Heart Journal 2010;31:463‐4.
Umemoto 2003 {published data only}
    1. Umemoto S, Kawahara S, Hashimoto R, Matsuzaki M. Angiotensin receptor blockers in chronic heart failure. Nippon Rinsho 2003;61(9):1683‐9. - PubMed
Uusimaa 2001 {published data only}
    1. Uusimaa P, Tokola H, Ruskoaho H, Vuolteenaho O, Risteli J, Ylitalo A, et al. Vasoactive peptides and procollagen propeptides in patients with hypertension in relation to cardiac hypertrophy and diastolic heart failure: design of the study and patient characteristics. Journal of Human Hypertension 2001;15 Suppl 1:S19‐22. - PubMed
Van den Berg 1993 {published data only}
    1. Berg MP, Veldhuisen DJ, Crijns HJ, Lie KI. Reversion of tachycardiomyopathy after beta‐blocker. Lancet 1993;341(8861):1667. - PubMed
Van den Berg 1995 {published data only}
    1. Berg MP, Crijns HJ, Veldhuisen DJ, Grief N, Kam PJ, Lie KI. Effects of lisinopril in patients with heart failure and chronic atrial fibrillation. Journal of Cardiac Failure 1995;1(5):355‐63. - PubMed
Vasiuk 2001 {published data only}
    1. Vasiuk IA, Kopelev MV, Khadzegova AB, Krikunov PV, Iushchuk EN, Sologub KN. The role of beta‐blockers in the treatment of chronic cardiac failure. Klinicheskaia Meditsina 2001;79(1):5‐8. - PubMed
Vincent 2012 {published data only}
    1. Vincent J, Sutradhar S, Beckerman B, Pitt B, Zannad F. Changes in sodium and renal function may contribute to the beneficial effects of eplerenone on mortality and morbidity in the EPHESUS trial. Circulation 2012;125(19):e745.
Vizir 2000 {published data only}
    1. Vizir VA, Berezin AE. Losartan in therapy of chronic heart failure. Klinicheskaia Meditsina 2000;78(2):36‐9. - PubMed
Vizzardi 2010 {published data only}
    1. Vizzardi E, D'Aloia A, Giubbini R, Bordonali T, Bugatti S, Pezzali N, et al. Effect of spironolactone on left ventricular ejection fraction and volumes in patients with class I or II heart failure. American Journal of Cardiology 2010;106(9):1292‐6. - PubMed
Vizzardi 2012 {published data only}
    1. Vizzardi E, D'Aloia A, Della Pina P, Lombardi C, Bonadei I, Rovetta R, et al. The effect of aldosterone‐antagonist therapy on aortic elastic properties in patients with moderate heart failure. European Heart Journal 2012;33:934.
Vizzardi 2015a {published data only}
    1. Vizzardi E, Sciatti E, Bonadei I, D'Aloia A, Tartiere‐Kesri L, Tartiere J M, et al. Effects of spironolactone on ventricular‐arterial coupling in patients with chronic systolic heart failure and mild symptoms. Clinical Research in Cardiology 2015;104(12):1078‐87. - PubMed
Vizzardi 2015b {published data only}
    1. Vizzardi E, Pina P D, Caretta G, Bonadei I, Sciatti E, Lombardi C, et al. The effect of aldosterone‐antagonist therapy on aortic elastic properties in patients with nonischemic dilated cardiomyopathy. Journal of Cardiovascular Medicine 2015;16(9):597‐602. - PubMed
Volpe 1992 {published data only}
    1. Volpe M, Tritto C, DeLuca N, Rubattu S, Mele AF, Lembo G, et al. Angiotensin converting enzyme inhibition restores cardiac and hormonal responses to volume overload in patients with dilated cardiomyopathy and mild heart failure. Circulation 1992;86(6):1800‐9. - PubMed
Volpe 2010 {published data only}
    1. Volpe M, Taddei S. The HEAAL study. Giornale Italiano di Cardiologia 2010;11(9):625‐9. - PubMed
Voors 2008 {published data only}
    1. Voors AA, Jong RM. Treating diastolic heart failure. Heart 2008;94(8):971‐2. - PubMed
Waagstein 2003 {published data only}
    1. Waagstein F, Stromblad O, Andersson B, Bohm M, Darius M, Delius W, et al. Increased exercise ejection fraction and reversed remodeling after long‐term treatment with metoprolol in congestive heart failure: a randomized, stratified, double‐blind, placebo‐controlled trial in mild to moderate heart failure due to ischemic or idiopathic dilated cardiomyopathy. European Journal of Heart Failure 2003;5(5):679‐91. - PubMed
Waldo 1995 {published data only}
    1. Waldo AL, Camm AJ, deRuyter H, Freidman PL, MacNeil DJ, Pitt B, et al. Survival with oral d‐sotalol in patients with left ventricular dysfunction after myocardial infarction: rationale, design, and methods (the SWORD trial). American Journal of Cardiology 1995;75(15):1023‐7. - PubMed
Waldo 1996 {published data only}
    1. Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, et al. Effect of d‐sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d‐Sotalol.[Erratum appears in Lancet 1996 Aug 10;348(9024):416]. Lancet 1996;348(9019):7‐12. - PubMed
Warner 1999 {published data only}
    1. Warner JG Jr, Metzger DC, Kitzman DW, Wesley DJ, Little WC. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. JACC 1999;33(6):1567‐72. - PubMed
Weinberg 2001 {published data only}
    1. Weinberg EO, Herzig JW. Management of hypertension and heart failure with AT1 receptor blockade. JPMA 2001;51(2):81‐5. - PubMed
Weintraub 2005 {published data only}
    1. Weintraub WS, Zhang Z, Mahoney EM, Kolm P, Spertus JA, Caro J, et al. Cost‐effectiveness of eplerenone compared with placebo in patients with myocardial infarction complicated by left ventricular dysfunction and heart failure. Circulation 2005;111(9):1106‐13. - PubMed
Weir 2011 {published data only}
    1. Weir RA, Tsorlalis IK, Steedman T, Dargie HJ, Fraser R, McMurray JJ, et al. Aldosterone and cortisol predict medium‐term left ventricular remodelling following myocardial infarction. European Journal of Heart Failure 2011;13(12):1305‐13. - PubMed
Wong 2002 {published data only}
    1. Wong M, Staszewsky L, Latini R, Barlera S, Volpi A, Chiang YT, et al. Valsartan benefits left ventricular structure and function in heart failure: Val‐HeFT echocardiographic study. JACC 2002;40(5):970‐5. - PubMed
Wong 2004 {published data only}
    1. Wong M, Staszewsky L, Latini R, Barlera S, Glazer R, Aknay N, et al. Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val‐HeFT) echocardiographic data. JACC 2004;43(11):2022‐7. - PubMed
Woodley 1991 {published data only}
    1. Woodley SL, Gilbert EM, Anderson JL, O'Connell JB, Deitchman D, Yanowitz FG, et al. Beta‐blockade with bucindolol in heart failure caused by ischemic versus idiopathic dilated cardiomyopathy. Circulation 1991;84(6):2426‐41. - PubMed
Wright 2014 {published data only}
    1. Wright LM, Jellis C, Kosmala W, Marwick T. Use of plasma markers of fibrosis to predict responders to the use of spironolactone in stage b heart failure: A strain analysis. JACC 2014;63(12):A1127.
Wu 2002 {published data only}
    1. Wu DQ, Yang YJ. Improving effect of carvedilol on cardiac function and exercise tolerance in patients with congestive heart failure of dilated cardiomyopathy. Chinese Journal of Clinical Rehabilitation 2002;6(15):2342‐3.
Xu 2007 {published data only}
    1. Xu JL, Zuo XH, Sha YB, Han CY, Liu XY, Zhang CJ. Effect of carvedilol on left ventricular function of patients with congestive heart failure evaluated by Doppler image. Journal of Clinical Rehabilitative Tissue Engineering Research 2007;11(13):2537‐9.
Yamamoto 2005 {published data only}
    1. Yamamoto T, Yano M. Aldosterone antagonist therapy for chronic heart failure. Nippon Naika Gakkai Zasshi 2005;94(2):262‐9. - PubMed
Yan 2012 {published data only}
    1. Yan ZL, Wei L, Zhong YM, Xie DM, Yang YH. Effects of benazepril on left ventricular remodelling and exercise tolerance in patients with valvular heart failure. Heart 2012;98:E262.
Yoshihiro 2011 {published data only}
    1. Yoshihiro I, Takaki T, Akira Y. The addition of direct renin inhibitor aliskiren to standard therapy suppresses enhanced cardiac sympathetic activity in patients with systolic heart failure. Circulation 2011;124(21):A8406.
Young 2004 {published data only}
    1. Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen‐Solal A, Dietz R, et al. Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low‐left ventricular ejection fraction trials. Circulation 2004;110(17):2618‐26. - PubMed
Zeng 2006 {published data only}
    1. Zeng QL, He L. Effectiveness of losartan and benazepril in improving diastolic function of left ventricle in patients with heart failure and hypertension. Pharmaceutical Care and Research 2006;6(4):294‐6.

References to studies awaiting assessment

Anonymous 2003d {published data only}
    1. Anonymous. Selective aldosterone blocking in heart failure. Eplerenone reduces the risk after infarction. MMW Fortschritte der Medizin 2003;145(44):42‐3. - PubMed
Botoni 2010 {published data only}
    1. Botoni F, Poole‐Wilson PPW, Ribeiro ALP, Guedes VC, Oliveira BMR, Teixeira MM, et al. Assessment of the Quality of Life (SF36) after optimized cardiovascular therapy in Chagas cardiomyopathy. European Journal of Heart Failure Supplement 2010;9:S108.
Dielievska 2015 {published data only}
    1. Dielievska VY. The effect of aldosterone receptor blockade in diastolic heart failure in patients with arterial hypertension combined with chronic obstructive pulmonary disease. General Medicine 2015;17(3):3‐7.
Gao 2010 {published data only}
    1. Gao WQ, Han CG, Zhao YX, Wang Q, Zhu P, Yang TS, et al. Effect of metoprolol on the expression of GRK2 in lymphocyte of advanced elderly patients with chronic heart failure. Nan Fang Yi Ke Da Xue Xue Bao 2010;30(5):1132‐3. - PubMed
Liu 2006 {published data only}
    1. Liu G, Ji Z, Liu K. Effects of spironolactone in treatment of elderly hypertensive patients with diastolic heart failure. Chinese Journal of New Drugs and Clinical Remedies 2006;25(8):567‐70.
Metra 1999 {published data only}
    1. Metra M, Nodari S, Bordonali T, Cagnazzi E, Boldi E, Dei Cas L. ACE‐inhibitors, AT1 receptor antagonists and diastolic dysfunction. Cardiologio 1999;44(Suppl 1):53‐8. - PubMed
Rapezzi 1999 {published data only}
    1. Rapezzi C, Perugini E, Amati S, Branzi A. Beta blockers and calcium antagonists in diastolic dysfunction. Cardiologia 1999;44(Suppl 1):61‐4. - PubMed
Zheng 2009 {published data only}
    1. Zheng Y, Meng L, Dong JS, Wu JY. Effect of carvedilol on heart function and glucolipometabolic in elder patients with diastolic heart failure. Journal of Jilin University (Medicine Edition) 2009;35(6):1111‐4.

References to ongoing studies

EudraCT 2013‐000867‐10 {published data only}
    1. EudraCT 2013‐000867‐10. Effects of spironolactone in heart failure with preserved ejection fraction: measured by CMR, echo, excercise capacity and quality of life questionaire [Effects of aldosterone antagonism in heart failure with preserved ejection fraction (HF‐PEF): cardiac MRI, echocardiography, exercise physiology & quality of life assessment]. www.clinicaltrialsregister.eu/ctr‐search/trial/2013‐000867‐10/GB (first received 13 February 2014).
IMPRESS‐AF {published data only}
    1. EudraCT 2014‐003702‐33. IMPRESS‐AF: IMproved exercise tolerance in patients with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation [Effect of spironolactone on ability to exercise and heart stiffness in people with irregular heart beats (atrial fibrillation) and normal pumping capacity of the heart]. www.clinicaltrialsregister.eu/ctr‐search/trial/2014‐003702‐33/GB (first entered 2 July 2015).
    1. ISRCTN10259346. IMPRESS‐AF: Improved exercise tolerance in heart failure with preserved ejection fraction by spironolactone on myocardial fibrosis in atrial fibrillation. www.isrctn.com/ISRCTN10259346 (first received 15 January 2015).
    1. NCT02673463. Spironolactone in atrial fibrillation (IMPRESS‐AF) [Improved exercise tolerance in participants with preserved ejection fraction by spironolactone on myocardial fibrosis in atrial fibrillation]. clinicaltrials.gov/show/NCT02673463 (first posted 4 February 2016).
    1. Shantsila E, Haynes R, Calvert M, Fisher J, Kirchhof P, Gill PS, et al. IMproved exercise tolerance in patients with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation rationale and design of the IMPRESS‐AF randomised controlled trial. BMJ Open 2016;6(10):e012241. - PMC - PubMed
NCT02901184 {published data only}
    1. NCT02901184. Spironolactone initiation registry randomized interventional trial in heart failure with preserved ejection fraction (SPIRRIT). clinicaltrials.gov/show/NCT02901184 (first posted 15 September 2016).
NCT03066804 {published data only}
    1. NCT03066804. A randomized, double‐blind controlled study comparing LCZ696 to medical therapy for comorbidities in HFpEF patients (PARALLAX) [A 24‐week, randomized, double‐blind, multi‐center, parallel group, active controlled study to evaluate the effect of LCZ696 on NT‐proBNP, symptoms, exercise function and safety compared to individualized medical management of comorbidities in patients with heart failure and preserved ejection fraction]. clinicaltrials.gov/show/NCT03066804 (first posted 28 February 2017).
    1. Tomasik A, Jachec W, Wojciechowska C, Kawecki D, Bialkowska B, Romuk E, et al. Randomized placebo controlled blinded study to assess valsartan efficacy in preventing left ventricle remodeling in patients with dual chamber pacemaker ‐ Rationale and design of the trial. Contemporary Clinical Trials 2015;42:239‐43. - PubMed
Zhou 2010 {published data only}
    1. Zhou J, Shi H, Zhang J, Lu Y, Fu M, Ge J, beta‐PRESERVE Study Investigators. Rationale and design of the beta‐blocker in heart failure with normal left ventricular ejection fraction (beta‐PRESERVE) study. European Journal of Heart Failure 2010;12(2):181‐5. - PubMed

Additional references

CIBIS Investigators 1999
    1. II CIBIS. The Cardiac Insufficiency Bisoprolol Study II (CIBIS‐II): a randomised trial. Lancet 1999;353(9146):9‐13. - PubMed
Consensus Trial Study Group 1987
    1. Group CONSENSUS Trial Study. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). New England Journal of Medicine 1987;316(23):1429‐35. - PubMed
de Denus 2017
    1. Denus S, O'Meara E, Desai AS, Claggett B, Lewis EF, Leclair G, et al. Spironolactone metabolites in TOPCAT ‐ new insights into regional variation. New England Journal of Medicine 2017;376(17):1690‐2. - PMC - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011.
Ezekowitz 2017
    1. Ezekowitz JA, O'Meara E, McDonald MA, Abrams H, Chan M, Ducharme A, et al. 2017 Comprehensive Update of the Canadian Cardiovascular Society Guidelines for the Management of Heart Failure. Canadian Journal of Cardiology 2017;33(11):1342‐433. - PubMed
Flather 2005
    1. Flather MD, Shibata MC, Coats AJ, Veldhuisen DJ, Parkhomenko A, Borbola J, et al. SENIORS Investigators. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). European Heart Journal 2005;26(3):215‐25. - PubMed
Gerber 2015
    1. Gerber Yariv, Weston Susan A, Redfield Margaret M, Chamberlain Alanna M, Manemann Sheila M, Jiang Ruoxiang, et al. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Internal Medicine 2015;175(6):996. - PMC - PubMed
GRADEpro GDT [Computer program]
    1. McMaster University (developed by Evidence Prime). GRADEpro GDT. Version accessed prior to 12 February 2018. Hamilton, ON: McMaster University (developed by Evidence Prime), 2015.
Granger 2003
    1. Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, et al. Effects of candesartan in patients with chronic heart failure and reduced left‐ventricular systolic function intolerant to angiotensin‐converting‐enzyme inhibitors: the CHARM‐Alternative trial. Lancet 2003;362(9386):772‐6. - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1 [updated March 2011]. The Cochrane Collaboration, 2011.
Hjalmarson 2000
    1. Hjalmarson A, Goldstein S, Fagerberg B, Wedel H, Waagstein F, Kjekshus J, et al. Effects of controlled‐release metoprolol on total mortality, hospitalizations, and well‐being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT‐HF). MERIT‐HF Study Group. JAMA 2000;283(10):1295‐302. - PubMed
Hogg 2005
    1. Hogg K, McMurray J. Neurohumoral pathways in heart failure with preserved systolic function. Progress in Cardiovascular Diseases 2005;47(6):357‐66. - PubMed
Kotecha 2014
    1. Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JGF, et al. Beta‐Blockers in Heart Failure Collaborative Group. Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual‐patient data meta‐analysis. Lancet 2014;384(9961):2235‐43. - PubMed
Lefebvre 2011
    1. Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
McMurray 2014
    1. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. PARADIGM‐HF Investigators and Committees. Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure. New England Journal of Medicine 2014;371(11):993‐1004. - PubMed
MERIT‐HF Study Group 1999
    1. MERIT‐HF. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT‐HF). Lancet 1999;353(9169):2001‐7. - PubMed
NCT01920711
    1. NCT01920711. Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON‐HF). clinicaltrials.gov/ct2/show/NCT01920711 (first posted 12 August 2013).
NCT02884206
    1. NCT02884206. Efficacy and Safety of LCZ696 Compared to Valsartan on Cognitive Function in Patients With Chronic Heart Failure and Preserved Ejection Fraction (PERSPECTIVE). clinicaltrials.gov/ct2/show/NCT02884206 (first posted 30 August 2016).
NICE 2010
    1. NICE. Chronic heart failure in adults: management. Retrieved from http://www.nice.org.uk/guidance/cg108/.
Packer 1999
    1. Packer M, Poole‐Wilson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, et al. Comparative effects of low and high doses of the angiotensin‐converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation 1999;100(23):2312‐8. - PubMed
Packer 2001
    1. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, et al. Effect of carvedilol on survival in severe chronic heart failure. New England Journal of Medicine 2001;344(22):1651‐8. - PubMed
Packer 2002
    1. Packer M, Fowler MB, Roecker EB, Coats AJS, Katus Hugo A, Krum H, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation 2002;106(17):2194‐9. - PubMed
Pfeffer 2015
    1. Pfeffer MA, Claggett B, Assmann SF, Boineau R, Anand IS, Clausell N, et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac FunctionHeart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation 2015;131(1):34‐42. - PubMed
Pitt 1999
    1. Pitt Bertram, Zannad Faiez, Remme Willem J, Cody Robert, Castaigne Alain, Perez Alfonso, et al. The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure. New England Journal of Medicine 1999;341(10):709‐17. - PubMed
Pitt 2014
    1. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. New England Journal of Medicine 2014;370(15):1383‐92. - PubMed
Ponikowski 2016
    1. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. Authors/Task Force Members. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal 2016;37(27):2129‐200. - PubMed
Rector 1995
    1. Rector T S, Tschumperlin L K, Kubo S H, Bank A J, Francis G S, McDonald K M, et al. Use of the Living With Heart Failure questionnaire to ascertain patients' perspectives on improvement in quality of life versus risk of drug‐induced death. Journal of Cardiac Failure 1995;1(3):201‐6. - PubMed
RevMan 2014 [Computer program]
    1. The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre: The Cochrane Collaboration, 2014.
Roger 2013
    1. Roger VL. Epidemiology of heart failure. Circulation Research 2013;113(6):646‐59. - PMC - PubMed
Rogers 2014
    1. Rogers JK, Pocock SJ, McMurray JJ, Granger CB, Michelson EL, Östergren J, et al. Analysing recurrent hospitalizations in heart failure: a review of statistical methodology, with application to CHARM‐Preserved. European Journal of Heart Failure 2014;16(1):33‐40. - PMC - PubMed
Sackner‐Bernstein 1995
    1. Sackner‐Bernstein JD, Mancini DM. Rationale for treatment of patients with chronic heart failure with adrenergic blockade. JAMA 1995;274(18):1462‐7. - PubMed
Sharma 2014
    1. Sharma K, Kass DA. Heart failure with preserved ejection fraction mechanisms, clinical features, and therapies. Circulation Research 2014;115:79‐96. - PMC - PubMed
Solomon 2012
    1. Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher‐Krainer E, et al. The angiotensin receptor neprilysin inhibitor LCZ696 inheart failure with preserved ejection fraction: a phase 2double‐blind randomised controlled trial. Lancet 2012;380:1387‐95. - PubMed
Solomon 2016
    1. Solomon Scott D, Claggett Brian, Lewis Eldrin F, Desai Akshay, Anand Inder, Sweitzer Nancy K, et al. Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction. European Heart Journal 2016;37(5):455‐62. - PMC - PubMed
SOLVD Investigators 1991
    1. SOLVD Investigators, Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. New England Journal of Medicine 1991;325(5):293‐302. - PubMed
SOLVD Investigators 1992
    1. SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. New England Journal of Medicine 1992;1992(327):685‐91. - PubMed
Spertus 2005
    1. Spertus J, Peterson E, Conard MW, Heidenreich PA, Krumholz HM, Jones P, et al. Cardiovascular Outcomes Research Consortium. Monitoring clinical changes in patients with heart failure: a comparison of methods. American Heart Journal 2005;150:707‐15. - PubMed
Wong 2006
    1. Wong SS, Wilczynski NL, Haynes RB. Developing optimal search strategies for detecting clinically sound treatment studies in EMBASE. Journal of the Medical Library Association 2006;94(1):41‐7. - PMC - PubMed
Yancy 2013
    1. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardioliology 2013;62(16):e147‐239. - PubMed
Yusuf 2003
    1. Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJV, et al. Effects of candesartan in patients with chronic heart failure and preserved left‐ventricular ejection fraction: the CHARM‐Preserved Trial. Lancet 2003;362(9386):777‐81. - PubMed
Zannad 2011
    1. Zannad F, McMurray JJV, Krum H, Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. New England Journal of Medicine 2011;364(1):11‐21. - PubMed
Zheng 2017
    1. Zheng SL, Chan FT, Nabeebaccus AA, Shah AM, McDonagh T, Okonko DO, et al. Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta‐analysis. Heart 2017;August:Epub ahead of print. - PMC - PubMed
Zile 2016
    1. Zile MR, Jhund PS, Baicu CF, Claggett BL, Pieske B, Voors AA, et al. Plasma biomarkers reflecting profibrotic processes in heart failure with a preserved ejection fraction: data from the prospective comparison of ARNI with ARB on management of heart failure with preserved ejection fraction study. Circulation. Heart Failure 2016;9(1):e002551. - PMC - PubMed

References to other published versions of this review

Lumbers 2017
    1. Lumbers RT, Martin N, Manoharan K, Nyong J, Thomas J, Casas JP, et al. Beta‐blockers and inhibitors of the renin‐angiotensin aldosterone system for chronic heart failure with preserved ejection fraction. Cochrane Database of Systematic Reviews 2017, Issue 7. [DOI: 10.1002/14651858.CD012721] - DOI - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources