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. 2024 Dec;13(4):707-736.
doi: 10.1007/s40119-024-00381-6. Epub 2024 Oct 25.

ACE Inhibitors and Angiotensin Receptor Blockers for the Primary and Secondary Prevention of Cardiovascular Outcomes: Recommendations from the 2024 Egyptian Cardiology Expert Consensus in Collaboration with the CVREP Foundation

Mohamed Sobhy  1   2   3 , Adel Eletriby  4 , Hany Ragy  5 , Hossam Kandil  6 , Mohamed Ayman Saleh  4 , Nabil Farag  4 , Ramez Guindy  4 , Ahmed Bendary  7 , Ahmed Mohamed Elmahmoudy Nayel  4 , Ahmed Shawky  4 , Ayman Khairy  8 , Ayman Mortada  4 , Bassem Zarif  5 , Haitham Badran  4 , Hazem Khorshid  4 , Kareem Mahmoud  6 , Karim Said  6 , Khaled Leon  5 , Mahmoud Abdelsabour  8 , Mazen Tawfik  4 , Mohamed Aboel-Kassem F Abdelmegid  8 , Mohamed Koriem  8 , Mohamed Loutfi  9   10 , Moheb Wadie  11 , Mohamed Elnoamany  12 , Mohamed Sadaka  9   10 , Mohamed Seleem  5 , Mohamed Zahran  4 , Osama A Amin  13 , Sameh Elkaffas  6 , Sherif Ayad  9   10 , Wael El Kilany  4 , Walid Ammar  6 , Waleed Elawady  14 , Walid Elhammady  4 , Yasser Abdelhady  13
Affiliations

ACE Inhibitors and Angiotensin Receptor Blockers for the Primary and Secondary Prevention of Cardiovascular Outcomes: Recommendations from the 2024 Egyptian Cardiology Expert Consensus in Collaboration with the CVREP Foundation

Mohamed Sobhy et al. Cardiol Ther. 2024 Dec.

Abstract

Introduction: The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in regulating blood pressure (BP), with dysregulation of RAAS resulting in hypertension and potentially heart failure (HF), myocardial infarction (MI), cardio-renal syndrome, and stroke. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), have advantages beyond BP control. However, differences between these two drug classes need to be considered when choosing a therapy for preventing cardiovascular events.

Methods: A panel of 36 Egyptian cardiologists developed consensus statements on RAAS inhibitors for primary and secondary prevention of cardiovascular outcomes and stroke, using a modified three-step Delphi process.

Results: The consensus statements highlight the importance of effective BP control and the role of RAAS blockade for prevention and management of various cardiovascular diseases. ACEis and ARBs differ in their mode of action and, thus, clinical effects. On the basis of available evidence, the consensus group recommended the following: ACEis should be considered as first choice (in preference to ARBs) to reduce the risk of MI, for primary prevention of HF, and for secondary prevention of stroke. ACEis and ARBs show equivalent efficacy for the primary prevention of stroke. Evidence also favors the preferential use of ACEis in patients with type 2 diabetes, for BP control, for the primary prevention of diabetic kidney disease, and to reduce the risk of major cardiovascular and renal outcomes. Treatment with an ACEi should be started within 24 h of ST segment elevation MI (and continued long term) in patients with HF, left ventricular systolic dysfunction, and/or diabetes. Angiotensin receptor/neprilysin inhibitors (ARNIs) are the first choice for patients with HF and reduced ejection fraction, with ACEis being the second choice in this group. ARBs are indicated as alternatives in patients who cannot tolerate ACEis. ACEis may be associated with cough development, but the incidence tends to be overestimated, and the risk can be reduced by use of a lipophilic ACEi or combining the ACEi with a calcium channel blocker.

Conclusion: RAAS blockade is an essential component of hypertension therapy; however, the protective effects provided by ACEis are superior to those of ARBs. Therefore, an ACEi is indicated in almost all cases, unless not tolerated.

Keywords: Angiotensin receptor blockers; Angiotensin-converting enzyme inhibitors; Cardiovascular outcomes; Heart failure; Hypertension; Myocardial infarction; Renin–angiotensin–aldosterone system; Stroke.

Plain language summary

Overstimulation of the renin–angiotensin–aldosterone system—a key regulator of blood pressure, and fluid and electrolyte balance—is known to cause an increase in blood pressure (also known as “hypertension”) and other diseases of the heart and blood vessels (the cardiovascular system). As such, treatments to block (or inhibit) this overstimulation are an essential part of medical strategies designed for the prevention of cardiovascular disease, especially in patients with hypertension (in whom the risk of death due to cardiovascular causes is high). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are two types of medication that block overstimulation of the renin–angiotensin–aldosterone system, but they work in different ways. Angiotensin-converting enzyme inhibitors are superior to angiotensin receptor blockers after heart attacks (acute myocardial infarction), in patients with heart failure, for the prevention of stroke in individuals who have already had a stroke, and in patients with diabetes. Both types of medication have beneficial effects on the kidneys and associated outcomes, but only angiotensin-converting enzyme inhibitors have been shown to significantly reduce death due to cardiovascular causes, as well as death due to any cause. Overall, the protective effects of angiotensin-converting enzyme inhibitors on the heart are substantially greater than those of angiotensin receptor blockers, meaning that treatment with an angiotensin-converting enzyme inhibitor is preferred in all patients, except those who cannot tolerate the side effects of this drug class.

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Conflict of interest statement

Declarations. Conflict of Interest: Mohamed Sobhy, Adel Eletriby, Hany Ragy, Hossam Kandil, Mohamed Ayman Saleh, Nabil Farag, Ramez Guindy, Ahmed Bendary, Ahmed Mohamed Elmahmoudy Nayel, Ahmed Shawky, Ayman Khairy, Ayman Mortada, Bassem Zarif, Haitham Badran, Hazem Khorshid, Kareem Mahmoud, Karim Said, Khaled Leon, Mahmoud Abdelsabour, Mazen Tawfik, Mohamed Aboel-Kassem F Abdelmegid, Mohamed Koriem, Mohamed Loutfi, Moheb Wadie, Mohamed Elnoamany, Mohamed Sadaka, Mohamed Seleem, Mohamed Zahran, Osama A. Amin, Sameh Elkaffas, Sherif Ayad, Wael El Kilany, Walid Ammar, Waleed Elawady, Walid Elhammady, and Yasser Abdelhady have nothing to disclose. Ethical Approval: As this study was classified as a consensus development technique and did not involve research on patients or patients’ data, obtaining approval from an ethics committee or internal review board was not necessary. All the clinicians who participated in this study are authors, who willingly served as panelists, agreed with the objectives of the modified Delphi panel study, and actively contributed to manuscript development. Doctors who filled in the Delphi questionnaire received an explanation about the project; they were informed about the intention to publish the results and were asked to complete the Delphi questionnaire if they agreed.

Figures

Fig. 1
Fig. 1
Literature search results and filtering
Fig. 2
Fig. 2
The renin–angiotensin–aldosterone system at a glance. Reproduced from Clarke and Turner (2012 [8]; https://doi.org/10.1155/2012/307315) under a CC-BY 3.0 license (https://creativecommons.org/licenses/by/3.0/). ACE(2) angiotensin-converting enzyme (2), Ang angiotensin, AT1R angiotensin II receptor type 1, AT2R angiotensin II receptor type 2, MMP matrix metalloproteinase, NADPH nicotinamide adenine dinucleotide phosphate, NEP neprilysin
Fig. 3
Fig. 3
Clinical studies showing the differing effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of acute myocardial infarction. Reproduced with permission from Dézsi and Szentes (2016) [34], under a CC-BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/). AMI acute myocardial infarction, CCB calcium channel blocker, CHARM-alt Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity Alternative study, CI confidence interval, EUROPA European Trial on Reduction of Cardiac Events with Perindopril in Patients with Stable Coronary Artery Disease study, HOPE Heart Outcomes Prevention study, HR hazard ratio, IDNT Irbesartan Diabetic Nephropathy Trial, NS non-significant, I-PRESERVE Irbesartan in Heart Failure with Preserved Ejection Fraction study, LIFE Losartan Intervention for Endpoint Reduction study, ONTARGET Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial, SCOPE Study on Cognition and Prognosis in the Elderly, VALUE Valsartan Antihypertensive Long-term Use Evaluation study
Fig. 4
Fig. 4
Presumed differences in mechanisms of action of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers with respect to myocardial infarction events. Elevated levels of plasminogen activator inhibitor-1 and decreased tissue plasminogen activator activity affect the coronary circulation causing coronary heart disease. Evidence suggests that bradykinin (which is increased by angiotensin-converting enzyme inhibitors only) stimulates tissue plasminogen activator and angiotensin-4 receptors (which are also only inhibited by angiotensin-converting enzyme inhibitors), which results in increased plasminogen activator inhibitor-1 secretion in endothelial cells. Reproduced with permission from Dézsi and Szentes (2016) [34], under a CC-BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/). ACE(I) angiotensin-converting enzyme (inhibitor), ARBs angiotensin receptor blockers, AT angiotensin; NO nitric oxide; PAI-1 plasminogen activator inhibitor-1, PGI2 prostaglandin I2, t-PA tissue plasminogen activator
Fig. 5
Fig. 5
Effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of all-cause and cardiovascular death, myocardial infarction, stroke, new-onset heart failure, and new-onset diabetes mellitus [45]. Reprinted from Savarese G et al. (2013) with permission from Elsevier. ACE-Is angiotensin-converting enzyme inhibitors, ARBs angiotensin receptor blockers, OR odds ratio
Fig. 6
Fig. 6
Treatment effects on all-cause mortality in studies of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on mortality (versus control). Used with permission of Oxford University Press. From Van Vark et al. [69]. Permission conveyed through Copyright Clearance Center, Inc. ACE angiotensin-converting enzyme, ADVANCE Action in Diabetes and Vascular Disease: Preterax and Diamicrom MR Controlled Evaluation, ALLHAT Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack, ANBP-2 Australian National Blood Pressure 2 study, ARB angiotensin receptor blockers, ASCOT-BPLA Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm, CASE-J Candesartan Antihypertensive Survival Evaluation in Japan, CI confidence interval, HIJ-CREATE Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease, HR hazard ratio, HYVET Hypertension in the Very Elderly Trial, IDNT Irbesartan Diabetic Nephropathy Trial, JMIC-B Japan Multicenter Investigation for Cardiovascular diseases-B, LIFE Losartan Intervention for Endpoint Reduction study, MOSES Morbidity and Mortality after Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention study, PROFESS Prevention Regimen for Effectively Avoiding Second Strokes study, RENAAL Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan study, SCOPE Study on Cognition and Prognosis in the Elderly, TRANSCEND, Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease, VALUE Valsartan Antihypertensive Long-term Use Evaluation study
Fig. 7
Fig. 7
Kaplan–Meier curves and adjusted hazard ratios for 2-year A all-cause death, B cardiac death, and C myocardial infarction in propensity score-matched patients with angiotensin receptor blockers versus angiotensin converting enzyme inhibitors. Reproduced from Lee LG et al. (2023 [117]; https://doi.org/10.1371/journal.pone.0281460) under a CC-BY 4.0 license (https://creativecommons.org/licenses/by/4.0/). ACEI angiotensin converting enzyme inhibitor, ARB angiotensin receptor blocker, CI confidence interval, HR hazard ratio
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