Kathleen Finn, MD, Daniel D. Dressler, MD, MSc, FHM

In a large meta-analysis, simvastatin and pravastatin were safest.

Because statins lower the incidence of adverse cardiovascular and cerebrovascular events — even in low-risk patients — they are used broadly (NEJM JW Gen Med Jun 12 2012). Statins' reported adverse effects include myalgias, myopathy, rhabdomyolysis, transaminitis, and diabetes mellitus. In a meta-analysis of 135 randomized trials (247,000 participants) that involved seven statins (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin [Crestor], simvastatin, and pitavastatin [Livalo]), investigators evaluated adverse effects associated with statins overall and individually.

The overall rate of statin discontinuation owing to adverse effects was low (6%) for all statins combined. Statins as a class caused no more medication discontinuations, myalgias, creatinine kinase elevations, myopathy, rhabdomyolysis, or cancer than placebo. However, statins significantly increased relative risk for transaminase elevations (by 50%; baseline incidence, 1%) and diabetes (by 9%) compared with placebo.

Simvastatin and pravastatin were associated with best overall tolerability and lowest discontinuation rates. Compared with controls, atorvastatin and rosuvastatin were associated with the highest discontinuation rate because of adverse events; whereas atorvastatin and fluvastatin were associated with higher risks for transaminase elevations (odds ratios, 2.6 and 5.2, respectively). Higher doses of all statins were associated with higher risk for transaminase elevations. Although low doses of simvastatin appeared to be safest, daily doses >40 mg significantly raised risk for creatinine kinase elevation (OR, 4.1) and transaminase elevation (OR, 2.8).

Citation(s):

Naci H et al. Comparative tolerability and harms of individual statins: A study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes 2013 Jul; 6:390.