Comparative Tolerability and Harms of Individual Statins

Naci H, Brugts J, Ades T
Circulation: Cardiovascular quality and outcome. July 9, 2013

Background

Previous meta-analyses have consistently demonstrated the effectiveness of statins for the primary and secondary prevention of cardiovascular disease in different subgroups [1-5]. The limits of treatment have expanded over time to include people at progressively lower risk of developing cardiovascular disease [6]. It is therefore important to know the comparative tolerability and harms of different statins.
No comprehensive analysis on the comparative adverse event profiles of different statins has been performed to date. Although the frequency of clinically significant side effects associated with statin therapy is low [7], having information on a more diverse range of outcomes would be beneficial to individuals receiving statins and clinicians informing those patients.
This study aimed to systematically review and synthesize the totality of the RCT evidence on different statins and to determine their comparative tolerability and harms across a range of populations eligible for statin therapy. The review included 135 trials, encompassing data on 246955 participants.

Main results

• In pairwise meta-analysis of placebo-controlled trials, statins as a class did not lead to more discontinuations because of adverse events than did control treatment (OR: 0.95, 95%CI: 0.83-1.08). Individual statins were similar to control with regard to discontinuation due to adverse events. Some differences were seen in head-to-head comparisons. Higher doses of statins did not necessarily result in higher discontinuation rates.
• In pairwise meta-analysis of placebo-controlled trials, statins did not significantly differ from control treatment with regard to incidence of myalgia (OR: 1.07, 95%CI: 0.89-1.29). Some differences were seen for myalgia incidence in head-to-head trials, although magnitude of the effect differed between trials. No apparent dose-response relationship for myalgia was observed for individual statin-dose combinations as compared with control treatment.
• Patients receiving statins had significantly higher odds of having alanine aminotransferase and aspartate aminotransferase elevations as compared to patients receiving placebo (OR: 1.51, 95%CI: 1.24-1.84). Certain statins were associated with higher odds of elevations of hepatic transaminases than others, and some dose-response relationships were seen.
• Statins as a class did not yield significant creatine kinase (CK) elevations, as compared to control treatment. Some individual statins resulted in clinically meaningful CK elevations, in some cases in a dose-responsive manner.
• Statins as a class did not show a different cancer incidence (5.2% of all participants), from control treatment (OR: 0.96, 95% credible interval in network analysis (CrI): 0.91-1.02), nor was an effect seen for individual statins.
• Pairwise placebo-controlled meta-analysis showed that statins as a class were associated with more diabetes mellitus than control treatment (OR: 1.09, 95%CrI: 1.02-1.16). No differences were detected in network analyses for individual statins.
• Although there was limited information, no significant differences were seen between statins and control for myopathy and rhabdomyolysis outcomes.

Conclusion

This network meta-analysis study provides evidence on the comparative tolerability and harms of individual statins. Overall, statins as a class are generally safe, with uncommon side-effects. Statin use is associated with an increased risk of diabetes mellitus and elevations of hepatic transaminases, but no statistically significant effects on myalgia, myopathy, rhabdomyolysis and cancer were detected. Differences exist between the safety profiles of individual statins, and these findings could help in prescription decision-making.

References

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