Side effects rare with statins, two types may have best safety profiles

Side effects associated with statin therapy are not common, and simvastatin and pravastatin may be safer and more tolerable than other drugs in the class, reported a meta-analysis that totaled nearly a quarter-million people.

Researchers systematically reviewed 55 two-armed placebo-controlled trials and 80 two- or multiarmed active-comparator trials that enrolled 246,955 individuals with and without cardiovascular disease to evaluate different statins. Results were published by Circulation: Cardiovascular Quality and Outcomes on July 9.

Individual statins showed no significant differences from controls for the following side effects :

• Myalgia: 43,531 participants, statins vs. controls, odds ratio (OR), 1.07 (95% CI, 0.89 to 1.29; I², 22.1%). Simvastatin had lower odds than atorvastatin (OR, 0.56; 95% CI, 0.42 to 0.75; I², 0.0%).
• Creatine kinase elevation: 101,324 participants, statins vs. controls, OR, 1.13 (95% CI, 0.85 to 1.51; I², 20.4%). Pitavastatin resulted in significantly more elevations than controls (OR, 3.63; 95% credible interval, 1.10 to 14.10).
• Discontinuations because of adverse events: 76,462 participants, statins compared to controls, OR, 0.95 (95% CI, 0.83 to 1.08; I², 21.9%). Simvastatin was significantly more tolerable than atorvastatin (OR, 0.61; 95% CI, 0.42 to 0.89; I², 71.9%) or rosuvastatin (OR, 0.49; 95% CI, 0.27 to 0.88; I², 0.0%).

Statins as a class resulted in significantly higher odds of diabetes (OR, 1.09; 95% CI, 1.02 to 1.16) and transaminase elevations (OR, 1.51; 95% CI, 1.24 to 1.84) compared with controls. However, there was no evidence of increased risk of cancer among 100,523 participants (OR, 0.96; 95% credible interval, 0.91 to 1.02; I², 0.0%), nor was there evidence of potential head-to-head differences between statins for these outcomes.

The researchers noted that when statins were compared, there were numerous statistically detectable differences favoring simvastatin and pravastatin. Dose-level comparisons showed there were higher odds of discontinuations with higher doses of atorvastatin and rosuvastatin, while higher doses of atorvastatin, fluvastatin, lovastatin and simvastatin were associated with higher odds of transaminase elevations. Simvastatin at its highest doses was associated with creatine kinase elevations (OR, 4.14; 95% credible interval, 1.08 to 16.24).

The researchers wrote, “At the population level, mortality and cardiovascular benefits of statin therapy greatly overweigh its potential harms, even taking into account the recent finding that statin use is associated with a modest increase in diabetes mellitus incidence. At the individual level, however, there may be a risk of exposing a large group of individuals to the (primarily minor) harms of statin therapy for the benefit of a smaller number of individuals. This brings into sharp focus the importance of correctly identifying the set of individuals who stand to benefit from statin therapy.”