Abstract 15658: Determinants of Residual Risk in 9,251 Secondary Prevention Patients Treated with High- versus Low-dose Statin Therapy: The Treating to New Targets (TNT) Study
CVD events continue to occur in statin-treated patients, albeit at a lower rate. Risk factors for this "residual risk" have not been studied comprehensively in a large, well-characterized cohort such as the Treating to New Targets (TNT) study. We aimed to identify clinical determinants of this residual risk above and beyond lipid risk factors.
Methods TNT participants were 10,001 secondary prevention patients with baseline LDL cholesterol <130 mg/dL randomized to double-blind therapy with atorvastatin 10 mg or 80 mg daily. This analysis included 9,251 patients (729 events) with complete on-treatment lipid data. Median follow-up was 4.9 years. The primary endpoint was a combined endpoint of major CVD (coronary death, non-fatal myocardial infarction, resuscitation after cardiac arrest, or fatal or non-fatal stroke). Significant determinants of residual risk were identified using Cox proportional hazards models and forward stepwise elimination.
Results High- versus low-dose atorvastatin resulted in a 22% relative risk reduction in the primary endpoint (P<0.001). Multivariate predictors of increased residual risk were older age, male gender, current smoking, hypertension, diabetes, prior CVD, calcium channel blocker use, body mass index (BMI), and baseline concentrations of apolipoprotein B and blood urea nitrogen (BUN), while predictors of lower risk were treatment allocation to high-dose statin, aspirin use and baseline apolipoprotein A-1 (Table, all P<0.01). Generally similar results were obtained after adjusting for on-treatment achieved concentrations of lipids and apolipoproteins.
Conclusion Residual risk in statin-treated secondary prevention patients is related to both lipid and non-lipid risk factors such as obesity, smoking, hypertension, diabetes, and BUN. A multi-faceted prevention approach should be adopted to address residual risk.
- © 2011 by American Heart Association, Inc.