CardioExchange Archive

Although clinical trials have consistently demonstrated the benefits of statins, especially in secondary prevention, the perception that the drugs can cause serious side effects has prompted some patients to discontinue or not take the drugs. Now, in a paper published in the European Journal of Preventive Cardiology, a new meta-analysis of existing trials offers some reassurance that most of the side effects that have been tied to statins do not appear to be actually caused by the drugs.

Researchers in the U.K. analyzed data from more than 83,00 patients randomized to statin therapy or placebo and found “little evidence of incremental symptomatic side effects beyond placebo,” though they did find a small absolute increase of 0.4% in people taking statins who had asymptomatic liver enzyme elevations.

The authors reported that although there were many reports of side effects often linked to statins, including myopathy, fatigue, muscle aches, and rhabdomyolysis, none occurred more often in the statin patients than in the placebo patients.

In 14 primary prevention trials, which included 46,262 randomized subjects, there was a small absolute 0.5% increase in the risk of diabetes in the statin group, but there was an absolute reduction of the same size in the risk of death. Overall, serious adverse events were reported in 14.6% of the statin group versus 14.9% of the placebo group.

In 15 secondary prevention trials, which included 37,618 randomized subjects, there was an absolute 1.4% decrease in the risk of death in the group taking statins. Overall, serious adverse events occurred in 9.9% of the statin group versus 11.2% of the placebo group.

In a separate analysis, the researchers analyzed data from five randomized trials that compared low-dose to high-dose statins. High-dose statins were associated with small but significant increases in asymptomatic liver enzymes, myopathy symptoms, and muscle aches. But high-dose statins were also associated with significant reductions in myocardial infarction and stroke.

The researchers acknowledge in their paper that the clinical trials used for their analysis may not fully reflect real-life clinical experience. Trials differ in the degree to which they search for and document side effects, and some investigators or sponsors “may not be motivated to search exhaustively for potential side effects.” In addition, people who qualify for or choose to participate in clinical trials may differ in important ways from real-life patients.

The authors concluded that “only a small minority of symptoms reported on statins are genuinely due to the statins: almost all reported symptoms occurred just as frequently when patients were administered placebo.”