Statins in Nonischemic Cardiomyopathy

Abstract & Commentary

By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.

Source: Sola S, et al. Atorvastatin Improves Left Ventricular Systolic Function and Serum Markers of Inflammation in Nonischemic Heart Failure. J Am Coll Cardiol. 2006;47:332-337.

Inflammatory cytokines are a feature of heart failure from any cause. Since statins inhibit the synthesis of inflammatory cytokines, Sola and colleagues hypothesized that they may benefit patients with nonischemic cardiomyopathy. They enrolled 108 stable patients with nonischemic heart failure and left ventricular ejection fraction (EF) < 35%, and randomized them to atorvastatin 20 mg a day or placebo (double blind) for 12 months. Diabetics were excluded. The primary end point was change in echocardiographic EF. Secondary end points included changes in inflammatory and oxidation markers.

Results: In the atorvastatin group, EF increased from a mean of 0.33 to 0.37 (P = 0.01), whereas EF declined in the placebo group (0.33 to 0.31). This was due to reductions in left ventricular systolic and diastolic dimensions in the atorvastatin group. Left ventricular size increased in the placebo group. Erythrocyte superoxide dismutase (E-SOD) increased, and serum high sensitivity C-reactive protein (hsCRP) interlukin-6 (IL-6) and tumor necrosis factor-alpha receptor II (TNF-x RII) decreased in the atorvastatin group (all P < 01). These markers were unchanged in the placebo group. As expected, there were significant reductions in LDL cholesterol and triglyceride in the atorvastatin group. Sola et al concluded that atorvastatin use in nonischemic cardiomyopathy abrogates adverse remodeling and improves EF. LDL cholesterol and inflammatory marker reductions may play a role in these effects.

Commentary

Prior observational studies have shown an association between statin therapy and mortality in heart failure. A smaller, randomized trial of simvastatin also showed increased ejection fraction and reduced inflammatory markers. Since inflammatory markers are associated with a worse outcome in large studies, this effect of statins may be the mechanism of the improved survival noted in observational studies and the improved EF noted in the Sola study. It is noteworthy that the Mozaffarian study did not show improvements in either the 6-minute walk test or the symptoms questionnaire. However, neither of the studies reported here were large enough nor long enough to adequately evaluate clinical outcomes.

Although cholesterol levels changed as expected with statin, those in the Sola study did not meet guidelines for treatment and, in the Mozaffarian study, the changes in cholesterol did not correlate with the changes in inflammatory markers. Interestingly, both trials focused on patients with nonischemic cardiomyopathy (100% Sola, > 90% Mozaffarian), which makes a cholesterol-related beneficial effect less likely. Also, in observational studies, lower cholesterol is associated with increased mortality in heart failure. Thus, the role of changes in lipid profile is unclear.

Should dilated cardiomyopathy patients be treated with statins regardless of lipid levels? Perhaps not at this time without any outcomes data, but if a patient were not doing well, I would consider it.

Statins in Heart Failure

Source: Mozaffarian D, et al. The Effects of Atorvastatin (10 mg) on Systemic Inflammation in Heart Failure. Am J Cardiol. 2005;96:1699-1704.

Statins have improved outcomes in heart failure patients in observational studies, but the mechanism is unknown. Thus, Mozaffarian and colleagues randomized 22 patients with nonischemic (20) and ischemic cardiomyopathy to atorvastatin 10 mg per day or placebo (double blind) for 16 weeks using a cross-over design at 8 weeks. The primary end points were inflammatory markers at baseline vs 8 weeks of therapy. Secondary end points included a heart failure symptoms questionnaire, a 6-minute walk, and various blood tests. Atorvastatin therapy reduced TNF 8%, CRP 37%, and endothelin 17%. IL-6 and brain natriuretic peptide were unchanged. Total cholesterol, LDL cholesterol, and triglycerides were decreased. There was no change in HDL cholesterol. Changes in cholesterol were not correlated with changes in inflammatory markers. Atorvastatin did not change serum catecholamine levels. Mozaffarian et al concluded that short-term atorvastatin therapy reduced levels of important inflammatory markers in patients with heart failure.