There is not enough evidence to use statins for primary prevention in those at low risk of cardiovascular disease. In addition, studies examining primary prevention need to be better designed, according to a meta-analysis by The Cochrane Collaboration published in January.
"A major limitation of the evidence summaries to date is the emphasis of the use of statins in secondary prevention of CVD [cardiovascular disease] without distinguishing between findings in primary prevention trials. More recently, however, a number of systematic reviews have focused their attention of the use of statins in primary prevention but they differ in their interpretation of the evidence to date," according to the authors, led by Fiona Taylor, MD, from the London School of Hygiene and Tropical Medicine in the U.K.
Taylor and colleagues analyzed 14 randomized controlled trials (16 trial arms; 34,272 participants) that compared statins with usual care or placebo. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria).
The inclusion criteria were randomized controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total LDL or HDL cholesterol levels, and where 10 percent or less had a history of cardiovascular disease.
The aim of researchers was to focus on specific events, rather than composite endpoints, and to include a higher number of healthy individuals than in previous reviews.
The authors wrote that "much useful data for this systematic review were lost" as a consequence of variances in trial designs, reported outcomes and biases. In addition, several trials were stopped early when their composite outcomes were reached.
Taylor and colleagues said that early discontinuation of trials "may lead to an over-estimation of treatment effects particularly when the number of events is small."
The researchers also suggested that caution needs to be taken with trials sponsored by pharmaceutical companies. In this review, all but one trial had some form of pharmaceutical industry sponsorship.
They said, "It is now established that published pharmaceutical industry-sponsored trials are more likely than non-industry-sponsored trials to report results and conclusions that favor drugs over placebo due to biased reporting and/or interpretation of trial results."
Additionally, in "primary prevention where world-wide the numbers of patients eligible for treatment are massive, there might be motivations to use composite outcomes and early stopping to get results that clearly support intervention."
In their review, Taylor and colleagues found that statins reduced all-cause mortality, coronary heart disease and stroke, and resulted in a reduction of revascularization rates.
They also saw a reduction in total cholesterol and LDL cholesterol in all trials, but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life.
However, "only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life" and "caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk."
They added, "Although reductions in all-cause mortality, composite endpoints and revascularizations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease," they concluded.
As far as the implications for future research, the investigators sounded this final note: "As newer statins are developed, it is likely that further trials will be conducted in lower risk populations to extend the evidence base, particularly among younger people with adverse risk factor profiles, which are associated with higher lifetime CVD risk. It is important that these trials examine potential adverse effects of statins and report on them in an unbiased way.
"Use of composite outcomes is reasonable given the small number of events arising among low-risk populations, but disaggregation of events by cause is helpful for better understanding of the effects of statins and for future systematic reviews of trials."