July 9th, 2013
Low Rate of Problems with Statins in Study of Quarter Million Patients
A very large analysis of previously published studies finds that statins are generally safe and well tolerated, but helps confirm previous links to a small increased risk for diabetes and elevation of liver enzymes. Some statins were better tolerated than others, and lower-dose statins were better tolerated than high doses.
In a paper published in Circulation: Cardiovascular Quality and Outcomes, Huseyin Naci and colleagues report their findings from a systematic review of clinical trials with statins for both primary and secondary prevention. The data from 135 trials included nearly 250,000 subjects, comparing statins with placebo or with other statins. Previous analyses have generally confirmed the overall benign profile of statins but have not explored in depth the differences between individual statins and the effect of different doses of individual statins.
The new study found no differences between statins and placebo in the rate of discontinuations due to myalgia, CK elevation, and cancer, but statins were associated with a higher risk for diabetes (OR 1.09, CI 1.02-1.16) and transaminase elevations (OR 1.51, CI 1.24-1.84).
“I am concerned that patients may misunderstand this small increase in risk and stop adhering to their medications,” said Naci in an AHA press release, concerning the diabetes finding.
Simvastatin and pravastatin were better tolerated than other statins, while atorvastatin and rosuvastatin were associated with more discontinuations. People taking high doses of atorvastatin, fluvastatin, lovastatin, and simvastatin were more likely to have transaminase elevations. People taking high-dose simvastatin had an increased risk for CK elevations.
In recent years, the value of statins for primary prevention has been the subject of intense controversy. The authors write that recent studies have confirmed “that all- cause mortality benefits of statins in the primary prevention setting are clinically and statistically significant.” The new study, they say, gives “supporting evidence for initiating statin therapy in individuals who are at an increased risk of developing cardiovascular disease.” However, they acknowledge that “expanding the limits of statin therapy to a wider population of individuals may have important safety implications. Although rare, adverse events associated with statin therapy range from mild to moderate, and appear to increase with treatment intensity.”
The authors also acknowledge that although their “review did not find statistical evidence of myopathy, this may be due to an under-detection of muscle toxicity in clinical trials.” They conclude:
Our findings have important clinical implications. First, there is strong evidence that statins as a class are generally safe with uncommon side effects. According to the findings of this comprehensive analysis, there is consistently strong evidence on the comparatively favorable side effect profile of simvastatin and pravastatin – particularly at low to moderate doses – which should be favored in clinical practice. This meta-analysis sheds new light on the discussion on the relation between statins and diabetes incidence and confirms that statin use is not associated with cancer incidence. Finally, 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.