Statins May Offer Unexpected Benefits in Heart Failure

Statins are well known for their lipid-lowering effects in coronary artery disease and heart attack prevention. But they've also shown benefits in heart failure, prompting some to ask: Is it the drugs' lipid-lowering properties that aid patients with heart failure? Or could it be other properties?

To find out, a research team led by Kumudha Ramasubbu, MD, reviewed 11 studies involving >120,000 patients with heart failure who took statins. Ramasubbu's team examined statins' effect on patient mortality, particularly whether the drugs differentially affected patients with ischemic versus nonischemic heart failure.

Their meta-analysis revealed that patients on statins had an almost 30% lower risk of mortality. What really intrigued them, though, was their primary finding: Nonischemic patients appeared to benefit from the statins just as much as their ischemic counterparts.¹

“We expected to see the benefit in ischemic cardiomyopathy [heart failure] because of cholesterollowering and plaque stabilization,” explains Ramasubbu, who presented the findings at the 11th Annual Scientific Meeting of the Heart Failure Society of America, September 16–19 in Washington, D.C. “But we were surprised to see this effect in nonischemic patients because their cardiomyopathy is not caused by atherosclerotic disease.”

BENEFITS AND SIDE EFFECTS

The findings indicate statins may help reverse heart failure through nonlipid-related pathways, says Ramasubbu, an assistant professor of medicine at Baylor College of Medicine in Houston. Statins as a class block the enzyme HMG-COA reductase, she says, which could provide a number of favorable effects.^2–4 These include:

1. A reduction in oxidative stress—cell damage or death caused by free radicals,

2. An improvement in blood vessel functioning and flow, and

3. A decrease in inflammation that appears to play a role in the development of heart failure.

Ramasubbu cautions, however, that these potential mechanisms of producing positive effects in heart failure have not yet been confirmed in research. And she adds an even bigger caveat: Other studies have revealed some side effects of statins that could pose problems in heart failure.

For example, at certain doses the drugs could lead to increases in bacterial endotoxins, thus provoking inflammation.⁵ They also could decrease production of selenoproteins, which may be involved in immune response.^6,7 And, finally, they could impede the antioxidant function of coenzyme Q10, a vitamin or vitamin-like substance that seems to play a key role in heart health, says Ramasubbu.^8–11

MORE ANSWERS NEEDED

However, such possible negative side effects should not discourage prescription of statins in heart failure, says Ramasubbu. But they do indicate that statins should be used very prudently with this population, she says.

“We need to keep in mind that the current study is a meta-analysis based on retrospective studies,” says Ramasubbu. “The results are hypothesis-generating but cannot be used as a treatment basis.”

What will be used as a treatment basis, however, are findings still to come from large randomized, prospective, placebo-controlled studies such as the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca heart failure trial (GISSI-HF), both under way.

These trials, says Ramasubbu, could provide answers to important questions concerning how aggressively to treat heart failure patients with statins—what dosages could provide the benefits without the negative effects. ▪