Assessment of Adverse Effects Attributed to Statin Therapy in Product Labels: A Meta-Analysis of Double-Blind Randomised Controlled Trials

This individual participant data meta-analysis included 23 large double-blind randomized trials with a total of 154,664 participants. The authors systematically evaluated 66 adverse effects listed in statin product labels. In addition to the beyond established risks of muscle symptoms and new-onset diabetes, the analysis found that statins were associated with significant excesses in only four outcomes: abnormal liver transaminases, other liver function test abnormalities, urinary composition changes, and edema. The absolute annual excess risks were small, generally less than 0.1 percent. Liver enzyme elevations showed a dose-response relationship, particularly with high-intensity atorvastatin; however, these evaluations were not linked to serious clinical hepatobiliary events. No causal associations were found for most labeled effects, including cognitive impairment, depression, sleep disturbances, sexual dysfunction, neuropathy, or renal injury. The authors concluded that current labeling overstates the harms and should be revised to more accurately reflect randomized evidence.