The efficacy of statin therapy in patients with established chronic heart failure (CHF) is a subject of much debate.
Methods and Findings
We conducted three systematic literature searches to assess the evidence supporting the prescription of statins in CHF. First, we investigated the participation of CHF patients in randomized placebo-controlled clinical trials designed to evaluate the efficacy of statins in reducing major cardiovascular events and mortality. Second, we assessed the association between serum cholesterol and outcome in CHF. Finally, we evaluated the ability of statin treatment to modify surrogate endpoint parameters in CHF.
Using validated search strategies, we systematically searched PubMed for our three queries. In addition, we searched the reference lists from eligible studies, used the “see related articles” feature for key publications in PubMed, consulted the Cochrane Library, and searched the ISI Web of Knowledge for papers citing key publications.
Search 1 resulted in the retrieval of 47 placebo-controlled clinical statin trials involving more than 100,000 patients. CHF patients had, however, been systematically excluded from these trials. Search 2 resulted in the retrieval of eight studies assessing the relationship between cholesterol levels and outcome in CHF patients. Lower serum cholesterol was consistently associated with increased mortality. Search 3 resulted in the retrieval of 18 studies on the efficacy of statin treatment in CHF. On the whole, these studies reported favorable outcomes for almost all surrogate endpoints.
Since CHF patients have been systematically excluded from randomized, controlled clinical cholesterol-lowering trials, the effect of statin therapy in these patients remains to be established. Currently, two large, randomized, placebo-controlled statin trials are under way to evaluate the efficacy of statin treatment in terms of reducing clinical endpoints in CHF patients in particular.
A systematic review found that patients with heart failure have been excluded from randomised controlled trials on the use of statins. Evidence from other studies on the effectiveness of statins for patients with heart failure is weak and conflicting.
When medical researchers test a drug—or some other treatment—for a particular medical condition, they often decide not to include in their study anyone who has, in addition to the disease they are interested in, certain other health problems. This is because including patients with two or more conditions can complicate the analysis of the results and make it hard to reach firm conclusions. However, excluding patients in this way can result in uncertainty as to whether treatments are effective for anyone who suffers from the disease in question, or just for people like those who took part in the research.
A great deal of research has been conducted with drugs known as statins, which lower cholesterol levels in the blood. (A raised level of cholesterol is known to be a major risk factor for cardiovascular disease, which causes heart attacks and strokes.) As a result of this research, statins have been accepted as effective and safe. They are now, in consequence, among the most commonly prescribed medicines. Heart failure, however, is not the same thing as a heart attack. It is the name given to the condition where the muscles of the heart have become weakened, most often as a result of aging, and the heart becomes gradually less efficient at pumping blood around the body. (Some people with heart failure live for many years, but 70% of those with the condition die within ten years.) It is common for people with cardiovascular disease also to have heart failure. Nevertheless, some researchers who have studied the effects of statins have made the decision not to include in their studies any patients with cardiovascular disease who, in addition, have heart failure.
Why Was This Study Done?
The researchers in this study were aware that patients with heart failure have often been excluded from statin trials. They felt it was important to assess the available evidence supporting the prescription of statins for such patients. Specifically, they wanted to find out the following: how often have patients with heart failure been included in statin trials, what evidence is available as to whether it is beneficial for patients with heart failure to have low cholesterol, and what evidence is there that prescribing statins helps these patients?
What Did the Researchers Do and Find?
They did not do any new work involving patients. Instead, they did a very thorough search for all relevant studies of good quality that had already been published and they reviewed the results. “Randomized clinical trials” (RCTs) are the most reliable type of medical research. The researchers found there had been 47 such trials (involving over 100,000 patients) on the use of statins for treating cardiovascular disease, but all these trials had excluded heart failure patients. They found eight studies (which were not RCTs) looking at cholesterol levels and heart failure. These studies found, perhaps surprisingly, that death rates were higher in those patients with heart failure who had low cholesterol. However, they also found 18 studies (again not RCTs) on the use of statins in patients with heart failure. These 18 studies seemed to suggest that statins were of benefit to the patients who received them.
What Do These Findings Mean?
The evidence for or against prescribing statins for people with heart failure is limited, conflicting, and unclear. Further research involving RTCs is necessary. (Two such trials are known to be in progress.)
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030333.
General information about statins is available from the Web site of Patient UK
The American Heart Association Web site is a good source of information about all types of heart disease, including heart attacks and heart failure
For a definition of randomized controlled trials see Wikipedia, a free online encyclopedia that anyone can edit
More detailed information about the quality of evidence from medical research may be found in the James Lind Library