Abstract and Introduction
Abstract
Background: Recent observations suggest statin treatment may be associated with lower mortality in heart failure (HF). The SCD-HeFT was a study of 2521 functional class II and III HF patients with left ventricular ejection fractions ≤35% and ischemic and nonischemic cardiomyopathy followed up for a median of 45.5 months. The study length, size, and degree of background HF, including the use of implantable defibrillator therapy, provide a unique opportunity to evaluate the impact of statin use in HF with mechanistic insights from subgroup analyses.
Methods and Results: Statin use was reported in 965 (38%) of 2521 patients at baseline and 1187 (47%) at last follow-up. The relationships between statin use, randomization arm, disease category, and functional class and all cause mortality were assessed. Statin use was studied as a time-dependent covariate in a multivariable Cox proportional hazards model, adjusted for imbalances between statin and no-statin groups. Mortality risk was significantly lower in those taking a statin (HR [95% CI], 0.70 [0.58-0.83]). Mortality risk was lower with statin use in all prespecified subgroups: ischemic cardiomyopathy (0.69 [0.56-0.86]), nonischemic cardiomyopathy (0.67 [0.47-0.96]), implantable cardioverter defibrillator (ICD) (0.66 [0.46-0.95], non-ICD (0.71 [0.57-0.87]), New York Heart Association II (0.62 [0.48-0.79]), and New York Heart Association III (0.79 [0.61-1.03]).
Conclusions: Statin use is associated with reduced all-cause mortality in HF patients. Statins appear to benefit patients with nonischemic and ischemic cardiomyopathy similarly. Statin benefits are similar in ICD and non-ICD patients.
Introduction
The safety and merit of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) in patients with heart failure (HF) has been an issue of debate. Statin trials have generally excluded patients with HF and, thus, did not establish the safety or efficacy of statins in this population. Low cholesterol levels have been associated with higher mortality in HF, raising concern that lipid lowering might be harmful. Statin medications have been associated with depletion of coenzyme Q10 and abnormal diastolic function. These issues have raised questions about the safety of treating HF patients with statins. On the other hand, statins may improve survival in patients with HF. Beneficial effects, observed in patients with ischemic and nonischemic HF, remain significant even after controlling for lipid status. Statins may improve autonomic tone, and have antiarrhythmic, and anti-inflammatory, benefits in HF.
The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) was a trial of 2521 patients with ischemic and nonischemic cardiomyopathy, functional class II and III HF, and left ventricular ejection fraction (LVEF) = 0.35, who were treated with standard HF medications and were then randomized to receive an implantable cardioverter defibrillator (ICD), amiodarone, or placebo. Background HF therapy in SCD-HeFT was excellent with >96% of patients on angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers and 69% of patients on ß-blockers. Statins were used widely throughout the study in patients with ischemic and nonischemic cardiomyopathy. This population, therefore, provided a rich opportunity to study trends in statin use and associations between statin use and mortality, with opportunities to glean mechanistic insights within subgroups.