Statins for Heart Failure?
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, and Chief of Clinical Cardiology, at the University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Source: Khush KK, et al. Effect of High-Dose Atorvastatin on Hospitalizations for Heart Failure. Circulation. 2007;115:576-583.
The role of statins in heart failure patients is poorly studied and controversial. Thus, Khush and colleagues analyzed the secondary endpoint in the Treating to New Targets (TNT) study of hospitalization for heart failure. TNT was a study of over 10,000 patients with stable coronary heart disease (CHD) treated with either 10 or 80 mg/day of atorvastatin and followed for about 5 years. The primary endpoint of cardiac death, myocardial infarction (MI) and stroke was reduced 22% by high-dose atorvastatin. A history of heart failure was obtained in 8% of the patients, however, advanced heart failure or an ejection fraction (EF) of < 30% were exclusion criteria. Patients with heart failure had more hypertension, diabetes, peripheral arterial disease, prior MI and stroke, and were on higher doses of renin-angiotensin-blocking drugs and diuretics. Baseline lipid panels were similar between those with and without a history of heart failure. Lipid/lipoprotein levels were lower in the atorvastatin 80-mg group except for high-density lipoprotein cholesterol which was not. Hospitalization for heart failure occurred in about 3% of the study population; 14% of those with a history of heart failure and 2% of those without. Heart failure portended a poor prognosis. In the atorvastatin 80-mg group, 2.4% were hospitalized for heart failure vs 3.3% in the atorvastatin 10-mg group (p < 0.02). This protective effect was strongest in those with a history of heart failure, but was not different in a variety of other subgroups. One-third of the patients who developed heart failure had angina or MI prior to the event as compared to 15% overall of patients who did not have heart failure. Hospitalization for heart failure decreased as low-density cholesterol decreased. There was no relation between heart failure and blood pressure. The authors concluded that intensive treatment with atorvastatin in stable CHD patients reduces the incidence of heart failure hospitalization as compared to less intensive treatment, but only in those with a history of heart failure. A reduction in coronary events did not seem to explain the results.
Commentary
Most large statin trials have excluded patients with heart failure, but interestingly they have shown a reduction in heart failure endpoints. Small studies of heart failure patients have also shown reduced heart failure endpoints. This study suggests a benefit in patients with a history of heart failure with high-dose atorvastatin, but not low dose. The mechanism of this effect is unclear. The heart failure benefit was associated withlowering LDL cholesterol levels, but those whose LDL decreased were mainly in the atorvastatin 80-mg group, so it could be an effect of high-dose atorvastatin alone. Since most of the heart-failure hospitalization patients did not have a preceding ischemic event, it is unlikely that an anti-ischemic effect is the mechanism. Other possible mechanisms that have been suggested include increased endothelial function, reduced inflammation, reduced sympathetic tone and reduced remodeling. There are no data in this study to support any particular mechanism.
One major limitation of the study was that left ventricular function measurements were not part of the protocol. Some patients had a known EF < 30% but they were excluded. Also, patients with advanced heart failure were excluded, so the results may not apply to them. In addition, evidence of silent ischemia was not sought. Finally, there may have been unrecognized confounders that skewed the results.
Since this was a study of stable CAD patients, it is likely that the plaque stabilization that markedly lowering LDL produces would lead to stabilization or actual improvement in left ventricular function. This is another reason why CAD patients, whatever their lipid profile, should be on statins. As one of my colleagues said of CAD patients, "Whatever their cholesterol is, it is too high for them."
The role of statins in heart failure patients is poorly studied and controversial. Thus, Khush and colleagues analyzed the secondary endpoint in the Treating to New Targets (TNT) study of hospitalization for heart failure.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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