Adverse events associated with individual statin treatments for cardiovascular disease: an indirect comparison meta-analysis

BACKGROUND: Statins are the most widely prescribed drug available. Due to this reason, it is important to understand the risks involved with the drug class and individual statins. AIM: We conducted a meta-analysis and employed indirect comparisons to identify differing risk effects across statins. DESIGN: We included any randomized clinical trial (RCT) of atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin used for cardiovascular disease event prevention. The main outcome was adverse events [all-cause mortality, cancers, rhabdomylosis, diabetes, aspartate and alanine aminotransferase (AST/ALT), and creatinine kinase (CK) increases beyond the upper limit of normal]. In order to evaluate the relative effects of each drug on adverse events, we calculated adjusted indirect comparisons of the adverse-event outcomes. RESULTS: Seventy-two trials involving 159,458 patients met our inclusion criteria. Overall, statin treatments significantly increased the rate of diabetes when compared to controls (OR: 1.09; 95% CI: 1.02-1.16) and elevated AST (OR: 1.31; 95% CI: 1.04-1.66) and ALT (OR: 1.28; 95% CI: 1.11-1.48) levels when compared to controls. Using indirect comparisons, we also found that atorvastatin significantly elevated AST levels compared to pravastatin (OR: 2.21; 95% CI: 1.13-4.29) and simvastatin significantly increased CK levels when compared to rosuvastatin (OR: 4.39; 95% CI: 1.01-19.07). Higher dose studies had increased risk of AST elevations. DISCUSSION: Although statins are generally well tolerated, there are risks associated with almost all drugs. With few exceptions, statins appear to exert a similar risk across individual drugs.