Muscle Pain in Statin Patients Is Usually Not Caused by the Drug

BARCELONA — Oft-reported muscle aches and pains attributed to regular statin use is most often something other than drug-related discomfort, according to a meta-analysis reported here.

Among 19 double-blind trials with over 120,000 patients, 27.1% of those who were receiving statins and 26.6% of those who were receiving placebo reported muscle pain or weakness over a weighted average median follow-up of 4.3 years (rate ratio [RR] 1.03, 95% CI 1.01-1.06), said Colin Baigent, FMedSci, of the University of Oxford in England, during a press conference at the European Society of Cardiology Congress. The study was also published in The Lancet.

Over 1 year, that translated to a 7% relative increase in reports of muscle pain or weakness among those randomized to a statin (RR 1.07, 95% CI 1.04-1.10), which corresponded to an absolute excess rate of 11 events per 1,000 person-years, indicating that only one in 15 reports by statin patients were actually due to the statin, Baigent noted. After 1 year, there was no significant excess in first reports of muscle pain or weakness (RR 0.99, 95% CI 0.96-1.02).

Muscle pain is almost insignificant compared with the proven benefits of statins for people with coronary artery disease, Baigent told MedPage Today.

“For most people taking a statin, any muscle-related symptoms they experience are not likely to be caused by the drug,” he said. “The known protective effects of statins against cardiovascular disease greatly exceed the slightly increased risk of muscle symptoms.”

“For every 1,000 people taking a moderate-intensity statin, the treatment would cause 11 generally mild episodes of muscle pain or weakness in the first year, with no significant excess in subsequent years,” Baigent explained. “Over a 5-year period, statins typically prevent 50 major vascular events in those with pre-existing vascular disease, and 25 major vascular events in those with no pre-existing vascular disease, with longer treatment yielding larger benefits.”

“These results should help doctors and patients to make informed decisions about whether to start or remain on statin therapy,” he said. “Information provided to doctors and patients should be reviewed in light of our findings, including drug labeling and guidelines.”

Commenting on the study, Manesh Patel, MD, of Duke University in Durham, North Carolina, told MedPage Today that clinicians should reassure patients who continue to experience pain after 1 year that it is unlikely due to statins.

“We should be getting the message out there that statins can prevent cardiac events,” he noted. “We need to do studies like this to provide the evidence, because there are large groups out there that are still talking a lot about these muscle pain issues, and there are a lot of people out there who cannot tolerate it. … Statins are among the most effective therapies we have that can benefit human health. We need to get them into more people.”

For this meta-analysis, Baigent and colleagues included randomized trials of statin therapy with at least 1,000 patients with a scheduled treatment duration of at least 2 years. They analyzed individual patient data from 19 double-blind trials of statin versus placebo (123,940 patients) and four double-blind trials of a more intensive versus a less intensive statin regimen (30,724 patients).

Among the four trials of more intensive versus less intensive statin therapy, they found that high-intensity regimens such as atorvastatin 40 to 80 mg daily or rosuvastatin 20 to 40 mg daily yielded a larger relative increase in the rate of muscle pain or weakness than less intensive or moderate-intensity regimens (RR 1.08 vs 1.03) compared with placebo, and a small excess was noted (1.05) for more intensive regimens after 1 year.

There was no clear evidence that the rate ratio was different for different statins, or in different clinical scenarios, the authors noted.

They acknowledged that there was considerable heterogeneity in the methods used to determine muscle symptoms in their meta-analysis, and definitions varied from trial to trial.