Large Study Affirms Safety of Statins

An analysis of trials including nearly a quarter of a million people confirmed that statins as a class are well tolerated, although safety profiles vary from agent to agent, researchers found.

Statin therapy was associated with increased odds of diabetes and elevations of liver enzymes compared with placebo, but there were no differences in development of myalgia or cancer, elevations in creatine kinase, or discontinuations because of adverse events, according to Huseyin Naci, MHS, of the London School of Economics and Political Science, and colleagues.

When comparing individual statins, simvastatin and pravastatin appeared to have the best safety profiles, and because of that they "should be favored in clinical practice," the investigators reported online in Circulation: Cardiovascular Quality and Outcomes.

But, they wrote, "we acknowledge the complex nature of making prescribing decisions and urge prescribers to consider the findings of this analysis in light of the comparative benefit profiles of individual statins in preventing all-cause mortality in addition to cardiovascular and cerebrovascular events."

The findings from the comparisons of individual statins should be interpreted with caution because they came from network meta-analyses, indicated Christie Ballantyne, MD, of Baylor College of Medicine in Houston.

"I think you just get into some problems with this methodology where I personally don't believe the conclusions are more valid than the studies which have all been published of the direct comparisons between statins," he said in an interview.

Nevertheless, the study confirms the tolerability of statins as a class, he said.

"There is this risk of some diabetes and you have to check some liver function tests, which we've known about, but I think it's reassuring to physicians and patients that this is a safe class of drugs," he said. "That's an important message because lots of people are stopping their medications. They get worried if they see things in the press, in the news. They stop taking their medicines, and then they're increasing their risk for having a cardiovascular event."

The study included information from 135 randomized trials -- 55 with a placebo control and 80 with an active comparator -- that included a total of 246,955 participants with or without cardiovascular disease. The study initially included trials of atorvastatin, fluvastatin, simvastatin, lovastatin, pravastatin, and rosuvastatin (Crestor); trials of pitavastatin (Livalo) were added post hoc because the protocol was already being finalized at the time the drug was approved.

In a meta-analysis of trials comparing the statins versus placebo, there were no differences in rates of discontinuation because of adverse events (OR 0.95, 95% CI 0.83-1.08), myalgia (OR 1.07, 95% CI 0.89-1.29), creatine kinase elevations (OR 1.13, 95% CI 0.85-1.51), and cancer (OR 0.96, 95% CI 0.91-1.02).

Consistent with prior studies, statin users had higher rates of diabetes (OR 1.09, 95% CI 1.02-1.16) and transaminase elevations (OR 1.51, 95% CI 1.24-1.84) compared with those who received placebo.

The comparisons between individual statins generally showed better safety and tolerability with simvastatin and pravastatin.

For example, simvastatin was associated with a decreased likelihood of stopping treatment because of adverse events in head-to-head trials with atorvastatin (OR 0.61, 95% CI 0.42-0.89) and rosuvastatin (OR 0.49, 95% CI 0.27-0.88). And in drug-level network meta-analyses, the odds of discontinuation were lower with pravastatin (OR 0.68, 95% CI 0.52-0.91) and simvastatin (OR 0.75, 95% CI 0.59-0.95) compared with atorvastatin.

The researchers also examined the effects of different doses of statins and found that the likelihood of discontinuation due to adverse events increased with higher doses of atorvastatin, the likelihood of transaminase elevations increased with higher doses of atorvastatin, fluvastatin, lovastatin, and simvastatin, and the likelihood of creatine kinase elevations rose with higher doses of lovastatin and simvastatin.

Although there was little information available regarding myopathy and rhabdomyolysis, available data did not suggest differences between the statins.

The authors acknowledged some limitations of their analysis, including the use of network meta-analyses, which assume that patient populations and trial characteristics are the same across studies, the lack of individual patient-level data, and the small amount of data available for some of the statins.

Source: www.medpagetoday.com