Assessment of adverse effects attributed to statin therapy in product labels: a meta-analysis of double-blind randomised controlled trials

Statin product labels (eg, Summaries of Product Characteristics [SmPCs]) list certain adverse outcomes as potential treatment-related effects based mainly on non-randomised and non-blinded studies, which might be subject to bias. We aimed to assess the evidence for such undesirable effects more reliably through a meta-analysis of individual participant data from large double-blind trials of statin therapy.

In this meta-analysis of individual participant-level data from double-blind randomised controlled trials, we generated a list of all undesirable effect terms listed in statin SmPCs by searching an electronic medicines compendium for five statins (atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin). Randomised trials were eligible for meta-analysis of these effects if they involved at least 1000 participants, had a scheduled treatment period of at least 2 years, and involved a double-blind comparison of statin versus placebo or of a more intensive versus a less intensive statin regimen. Event rate ratios (RRs) and 95% CIs were calculated with statistical significance assessed after controlling the false discovery rate (FDR) at 5%.