Determinants of Residual Risk in Secondary Prevention Patients Treated with High- Versus Low-Dose Statin Therapy: The Treating to New Targets (TNT) Study
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—9,251 coronary patients with LDL cholesterol<130 mg/dL randomized to double-blind atorvastatin 10 or 80 mg/day 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 endpoint was major cardiovascular events (n=729): coronary death, non-fatal myocardial infarction, resuscitation after cardiac arrest, or fatal or non-fatal stroke. Multivariable determinants of increased risk were older age (adjusted hazard ratio 1.13 per 1-SD [8.8 years], 95% CI 1.04-1.23), increased body-mass index (BMI) (1.09, 1.02-1.17 per 4.5 kg/m2), male gender (1.33, 1.07-1.65), hypertension (1.38, 1.17-1.63), diabetes (1.33, 1.11-1.60), baseline apolipoprotein B (1.19, 1.11-1.28 per 19 mg/dL) and blood urea nitrogen (1.10, 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 (0.82, 0.70-0.94), aspirin use (0.67, 0.56-0.81), and baseline apolipoprotein A-I (0.91, 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 non-cases (Harrell's c-index=0.679).
Conclusions—Determinants of residual risk in statin-treated secondary prevention patients included lipid-related and non-lipid factors such as baseline apolipoproteins, increased BMI, smoking, hypertension, and diabetes. A multi-faceted prevention approach should be underscored to address this risk.
Clinical Trial Registration Information—clinicaltrials.gov; Unique identifier: NCT00327691
- Received December 19, 2011.
- Accepted February 23, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited