Safety Profile of Atorvastatin 80 mg: A Meta-Analysis of 17 Randomized Controlled Trials in 21,910 Participants

Atorvastatin 80 mg/day has significant benefits for the primary and secondary prevention of cardiovascular and cerebrovascular disease. To our knowledge, no meta-analysis focusing on assessing the safety profile of atorvastatin 80 mg/day has been performed; therefore, our aim was to evaluate the tolerability and adverse event (AE) patterns of this drug/dose.

We conducted a search of the Cochrane Library, EMBASE and PubMed databases through to July 2015 for randomized controlled trials (RCTs). The safety endpoints included the incidence of discontinuations due to AEs, transaminase elevation, creatine kinase (CK) elevation, myalgia and rhabdomyolysis. We also conducted subgroup analyses according to the length of follow-up and clinical condition.

Data from 17 RCTs involving 21,910 participants were included. Pooled analyses showed that atorvastatin 80 mg/day was less tolerable [risk ratio (RR) 1.29, 95 % confidence interval (CI) 1.17-1.42] and increased the risk of transaminase elevation (RR 4.59, 95 % CI 3.26-6.48) compared with controls. No significant difference was observed between the two groups in terms of the incidence of CK elevation (RR 1.38, 95 % CI 0.97-1.95), myalgia (RR 1.06, 95 % CI 0.93-1.20), and rhabdomyolysis (RR 0.67, 95 % CI 0.19-2.36).

Patients treated with atorvastatin 80 mg/day, specifically patients with coronary artery disease (CAD), have a higher risk of transaminase elevation, which is not seen if patient exposure is less than 16 weeks. Atorvastatin 80 mg/day is less well-tolerated compared with controls, especially in patients with CAD, but an overall favorable tolerability profile is found if patient exposure is less than 52 weeks.