Determinants of Residual Risk in Secondary Prevention Patients Treated With High- Versus Low-Dose Statin Therapy The Treating to New Targets (TNT) Study

• Authors: Samia Mora, Brigham and Women's Hospital; Nanette Wenger, Emory University; David A. DeMicco, Pfizer; Andrei Breazna, Pfizer; S. Matthijs Boekholdt, University of Amsterdam; Benoit J. Arsenault, University of Amsterdam; Prakash Deedwania, University of California San Francisco; John J.P. Kastelein, University of Amsterdam; David D. Waters, University of California San Francisco
• Journal Title: Circulation
• Volume: Volume 125, Number 16
• Publisher: American Heart Association | 2012-04-24, Pages 1979-+
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1161/CIRCULATIONAHA.111.088591
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Peripheral Vascular Disease; Cardiovascular System & Cardiology; apolipoproteins; risk factors; risk assessment; secondary prevention; DENSITY-LIPOPROTEIN CHOLESTEROL; HDL CHOLESTEROL; CARDIOVASCULAR EVENTS; LDL CHOLESTEROL; CORONARY; PARTICIPANTS; METAANALYSIS; EFFICACY; SAFETY

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), 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.