Short-Term Statin Therapy Improves Cardiac Function and Symptoms in Patients With Idiopathic Dilated Cardiomyopathy

Abstract

Background— Chronic heart failure is associated with inflammation and neurohormonal imbalance. The 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, or statins, exert anti-inflammatory and vascular protective effects. We hypothesized that short-term statin therapy may have beneficial effects in patients with nonischemic heart failure. Methods and Results— Sixty-three patients with symptomatic, nonischemic, dilated cardiomyopathy were randomly divided into 2 groups. One group received simvastatin (n=24), and the other group received placebo (n=27). The initial dose of simvastatin was 5 mg/d, which was increased to 10 mg/d after 4 weeks. After 14 weeks, patients receiving simvastatin exhibited a modest reduction in serum cholesterol level compared with patients receiving placebo (130±13 versus 148±18, P <0.05). Patients treated with simvastatin had a lower New York Heart Association functional class compared with patients receiving placebo (2.04±0.06 versus 2.32±0.05, P <0.01). This corresponded to improved left ventricular ejection fraction in the simvastatin group (34±3 to 41±4%, P <0.05) but not in the placebo group. Furthermore, plasma concentrations of tumor necrosis factor-α, interleukin-6, and brain natriuretic peptide were significantly lower in the simvastatin group compared with the placebo group. Conclusions— Short-term statin therapy improves cardiac function, neurohormonal imbalance, and symptoms associated with idiopathic dilated cardiomyopathy. These findings suggest that statins may have therapeutic benefits in patients with heart failure irrespective of serum cholesterol levels or atherosclerotic heart disease.

Atorvastatin Therapy Is Associated with Reduced Levels of N‐terminal Prohormone Brain Natriuretic Peptide and Improved Cardiac Function in Patients with Heart Failure

“…5 -7 Moreover, statins were shown to improve cardiac function in patients with nonischemic dilated cardiomyopathy. 8,9 As in the present study, total cholesterol was significantly lower in the atorvastatin group and there was a trend towards significance for lower cholesterol in the other statin group. It cannot be entirely excluded that improved plasma lipid profile, at least partially, accounts for better outcomes.…”

“…Laufs et al randomized 14 patients with dilated cardiomyopathy to cerivastatin or placebo, and followed them for 20 wk. 8 Both standardized life quality and exercise capacity increased significantly in the statin group. Node et al examined the effect of simvastatin in 23 patients with nonischemic HF, and found improved EF and slightly (approx.…”

“…19 -21 However, both pravastatin and simvastatin were demonstrated to exert HF-relevant pleiotropic functions and, moreover, treatment with simvastatin improved cardiac function in patients with dilated cardiomyopathy, irrespective of reduced cholesterol levels. 8 It has to be pointed out that HF patients investigated here received statin treatment at doses commonly administered in clinical practice in Germany. Forty mg simvastatin is equivalent to only 15 mg atorvastatin; at least with respect to lipid-lowering effects.…”

Spectrum of Pleiotropic Effects of Statins in Heart Failure

“…A statistically significant change was not observed in the placebo group. [26] Thus, by altering the regulation of nitric oxide and endothelin, statins may have a beneficial effect on endothelial function and systemic peripheral vascular resistance.…”

Protective effects of statin on cardiac fibrosis and apoptosis in adrenomedullin-knockout mice treated with angiotensin II and high salt loading

“…10 Statins effectively improve cardiac function and increase the survival rate in patients with severe cardiac failure due to dilated cardiomyopathy without coronary arterial insufficiency. 13,14 In addition, statins upregulate and activate endothelial nitric oxide synthase (eNOS) and increase NO production through the PI3K-Akt-eNOS pathway. 15,16 Statins inhibit the formation of mevalonate and exhibit powerful anti-inflammatory effects, mediated by the inhibition of critical proteins such as Ras, Rho and NF-kB.…”