Statin therapy is used to prevent atherosclerotic cardiovascular disease, but concerns persist that statins may cause adverse muscle effects, including pain or weakness. A meta-analysis was conducted to evaluate the causal effects of statin therapy on muscle events of differing types and severity and to explore how any excess risk varied over time, in different types of patients, and with different statin regimens.

Individual participant data were available from 19 randomized double-blind trials of any statin regimen versus placebo (123,940 patients) and four randomized double-blind trials of more-intensive versus less-intensive statin regimens (30,724 patients).

In the 19 trials comparing statins with placebo, the mean age of the participants was 63 years; 28% were women, 48% had previous vascular disease, and 18% had diabetes. During a median follow-up period of 4.3 years, 27.1% of participants who were assigned a statin reported at least one episode of muscle pain or weakness compared with 26.6% of those assigned placebo, which corresponds to a 3% relative increase. During the first year of statin therapy, there was a 7% relative increase in muscle pain or weakness, corresponding to an absolute excess rate of 11 events of muscle pain or weakness per 1,000 person-years. This indicates that only one in 15 reports of muscle symptoms was attributable to statin therapy. After the first year of treatment, there was no significant increase in reports of muscle symptoms.

The researchers found that different types of statins of equivalent lipid-lowering ability had similar effects on muscle symptoms, and the effects were similar in different types of patients. More-intensive regimens caused a greater increase in muscle symptoms than moderate-intensity regimens in the first year, and there was some evidence that a small excess risk of muscle symptoms with more-intensive regimens might persist after the first year. Participants treated with statins had a small increase in median creatine kinase values.

Methods varied from trial to trial, the researchers note, and data on adverse events weren't available for all trials. Most reports of muscle pain didn't include creatine kinase values, and most trials didn't exclude patients who would be considered statin intolerant.