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Randomized Controlled Trial
. 2012 Apr 24;125(16):1979-87.
doi: 10.1161/CIRCULATIONAHA.111.088591. Epub 2012 Mar 29.

Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the Treating to New Targets (TNT) study

Samia Mora  1 , Nanette K Wenger, David A Demicco, Andrei Breazna, S Matthijs Boekholdt, Benoit J Arsenault, Prakash Deedwania, John J P Kastelein, David D Waters
Affiliations
Randomized Controlled Trial

Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the Treating to New Targets (TNT) study

Samia Mora et al. Circulation. .

Abstract

Background: Cardiovascular events occur among statin-treated patients, albeit at lower rates. Risk factors for this "residual risk" have not been studied comprehensively. We aimed to identify determinants of this risk above and beyond lipid-related risk factors.

Methods and results: A total of 9251 coronary patients with low-density lipoprotein cholesterol <130 mg/dL randomized to double-blind atorvastatin 10 or 80 mg/d in the Treating to New Targets (TNT) study had complete on-treatment 1-year lipid data. Median follow-up was 4.9 years. The primary end point was major cardiovascular events (n=729): coronary death, nonfatal myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. Multivariable determinants of increased risk were older age (adjusted hazard ratio [aHR], 1.13 per 1 SD [8.8 years]; 95% confidence interval [CI], 1.04-1.23), increased body mass index (aHR, 1.09; 95% CI, 1.02-1.17 per 4.5 kg/m(2)), male sex (aHR, 1.33; 95% CI, 1.07-1.65), hypertension (aHR, 1.38; 95% CI, 1.17-1.63), diabetes mellitus (aHR, 1.33; 95% CI, 1.11-1.60), baseline apolipoprotein B (aHR, 1.19; 95% CI, 1.11-1.28 per 19 mg/dL), and blood urea nitrogen (aHR, 1.10; 95% CI, 1.03-1.17 per 4.9 mg/dL), in addition to current smoking, prior cardiovascular disease, and calcium channel blocker use. Determinants of decreased risk were high-dose statin (aHR, 0.82; 95% CI, 0.70-0.94), aspirin use (aHR, 0.67; 95% CI, 0.56-0.81), and baseline apolipoprotein A-I (aHR, 0.91; 95% CI, 0.84-0.99 per 25 mg/dL). On-treatment 1-year lipids or apolipoproteins were not additionally associated with risk in multivariable models. Known baseline variables performed moderately well in discriminating future cases from noncases (Harrell c index=0.679).

Conclusions: Determinants of residual risk in statin-treated secondary prevention patients included lipid-related and nonlipid factors such as baseline apolipoproteins, increased body mass index, smoking, hypertension, and diabetes mellitus. A multifaceted prevention approach should be underscored to address this risk.

Clinical trial registration: URL: http://clinicaltrials.gov. Unique identifier: NCT00327691.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mora has received research grant support from AstraZeneca and Merck, served as a consultant for Pfizer and Quest Diagnostics, and received non-promotional speaker honorarium from Abbott and AstraZeneca. Dr Wenger has received research grants from Merck, Gilead Sciences (formerly CV Therapeutics), Pfizer, NHLBI, Abbott and Eli Lilly, and has served as a consultant/advisory board member or received honoraria from Astra Zeneca, Gilead Sciences (formerly CV Therapeutics), Abbott, Merck, Pfizer, and Medtronic. Dr DeMicco and Dr Breazna are employees of Pfizer. Dr Boekholdt and Dr Arsenault have served as consultant/advisory board members for Pfizer. Dr Deedwania has received research grant support from Pfizer and served as consultant/advisory board member of Pfizer and Novartis. Dr Kastelein has served as consultant/advisory board member of Pfizer. Dr Waters has served as consultant/advisory board member of Merck Schering-Plough, Genetech, Aegerion, Roche, Sanofi-Aventis, Pfizer, and Anthera.

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