Statins for Heart Failure – Not so Fast!

Implications:  

Implications:

• Evidence suggests that statins produce potentially beneficial actions in heart failure, independent of lipid lowering.
• Clinical trials of statins in heart failure (independent of cholesterol levels) have been called for.
• Rosuvastatin (Crestor, AstraZeneca) failed to show any beneficial effects on cardiac remodeling, i.e., cardiac structure, function, or size.
• These results are discouraging as without favorably affecting cardiac remodeling, beneficial effects on clinical outcomes are less likely.
• Further large trials focusing on clinical outcomes are needed, but initial optimism is diminished.

Analysis:

Henry Krum MBBS, PhD, FRACP, Emma Ashton BSc, PhD, Christopher Reid BA, MSc, PhD, Victor Kalff MBBS, FRACP, Jim Rogers MBBS, FRACP, John Amarena MBBS, FRACP, Bhuwan Singh MBBS, FRACP and Andrew Tonkin MBBS, MD, FRACP . Double-Blind, Randomized, Placebo-Controlled Study of High-Dose HMG CoA Reductase Inhibitor Therapy on Ventricular Remodeling, Pro-Inflammatory Cytokines and Neurohormonal Parameters in Patients With Chronic Systolic Heart Failure. J Card Fail. 2007 Feb;13(1):1-7

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WHG-4N5TM58-5&_user=10&_coverDate=02%2F28%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=b5ebb421b7f9a8896ea64e2777d47928

Statins reduce mortality in patients with coronary artery disease, but patients with overt heart failure (HF) are often excluded from trials. Because statins possess pharmacologic properties, other than lipid lowering, that may be beneficial on ventricular remodeling in HF, a study of rosuvastatin (ROS - Crestor, AstraZeneca) was carried out in patients with HF and left ventricular ejection fraction (LVEF) <40%.Compared to 46 patients on placebo, 40 patients on ROS experienced a decrease in LDL cholesterol, but there was no significant change in LVEF, cardiac contractility, or heart volume on either treatment, indicating no effect on cardiac remodeling, an important correlate of clinical improvement in HF trials. There were also no effects on symptoms, hospitalizations for HF, or death. The authors concluded that, “despite being safe and effective at decreasing plasma cholesterol, high-dose ROS did not beneficially alter parameters of LV remodeling. Reasons for absence of benefit are uncertain, but may include patient population studied…”

I have been writing in these pages about the potential benefits of statins in heart failure (HF) independent of their cholesterol lowering effect. Most of the supportive data derives from trials of statins in patients with hyperlipidemia and a past history of HF or with risk factors for HF, but usually not with overt HF. Other support comes from animal studies or observational studies. Based on this evidence large randomized clinical trials have been called for. This is the first report of such a trial conducted in patients with symptomatic HF and cardiac dysfunction, and no requirement for hypercholesterolemia. The results are discouraging as the primary endpoint of cardiac remodeling was not altered. Cardiac remodeling indicates adverse changes in cardiac structure, size, and function. Most successful clinical trials (such as beta-blockers or ACE-inhibitors) have shown arrest or reversal of remodeling, which has been associated with improved symptoms and reduced hospitalizations and deaths. Thus, the present results raise concern about the potential for statins to favorably impact clinical outcomes in HF. Further large trials focused on clinical outcomes are needed, but in the meantime, the present results dampen one’s enthusiasm, even mine!