A Survey of the FDA's AERS Database Regarding Muscle and Tendon Adverse Events Linked to the Statin Drug Class

Keith B Hoffman,Beatrice A Golomb,Christina Kraus,Mo Dimbil,James M Wright

doi:10.1371/journal.pone.0042866

Abstract

BackgroundCholesterol management drugs known as statins are widely used and often well tolerated; however, a variety of muscle-related side effects can arise. These adverse events (AEs) can have serious impact, and form a significant barrier to therapy adherence. Surveillance of post-marketing AEs is of vital importance to understand real-world AEs and reporting differences between individual statin drugs. We conducted a review of post-approval muscle and tendon AE reports in association with statin use, to assess differences within the drug class.MethodsWe analyzed all case reports from the FDA AE Reporting System (AERS) database linking muscle-related AEs to statin use (07/01/2005–03/31/2011). Drugs examined were: atorvastatin, simvastatin, lovastatin, pravastatin, rosuvastatin, and fluvastatin.ResultsRelative risk rates for rosuvastatin were consistently higher than other statins. Atorvastatin and simvastatin showed intermediate risks, while pravastatin and lovastatin appeared to have the lowest risk rates. Relative risk of muscle-related AEs, therefore, approximately tracked with per milligram LDL-lowering potency, with fluvastatin an apparent exception. Incorporating all muscle categories, rates for atorvastatin, simvastatin, pravastatin, and lovastatin were, respectively, 55%, 26%, 17%, and 7.5% as high, as rosuvastatin, approximately tracking per milligram potency (Rosuvastatin>Atorvastatin>Simvastatin>Pravastatin≈Lovastatin) and comporting with findings of other studies. Relative potency, therefore, appears to be a fundamental predictor of muscle-related AE risk, with fluvastatin, the least potent statin, an apparent exception (risk 74% vs rosuvastatin).InterpretationAE reporting rates differed strikingly for drugs within the statin class, with relative reporting aligning substantially with potency. The data presented in this report offer important reference points for the selection of statins for cholesterol management in general and, especially, for the rechallenge of patients who have experienced muscle-related AEs (for whom agents of lower expected potency should be preferred).

Highlights

We sought to analyze the FDA Adverse Event Reporting System (AERS) database in order to: (i) examine relative rates of statin side effects across muscle and tendon categories, and (ii) determine if meaningful safety differences might exist between the six main statin drugs.While others have analyzed controlled clinical trials undertaken with this class of drugs, this analysis was designed to assess links between these drugs and adverse events in large, heterogeneous ‘‘real-world’’ patient populations, by analyzing over seven-years of FDA adverse event case reports.Many studies have focused on one serious statin side effect, rhabdomyolysis
Drugs selected for analysis were: atorvastatin (Lipitor), simvastatin (Zocor), lovastatin (Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor), fluvastatin (Lescol), and generic equivalents and foreign designations
Rosuvastatin and fluvastatin appeared to be consistently linked to higher adverse event relative risks than other commonly used statins, while atorvastatin and simvastatin showed intermediate risks, and pravastatin and lovastatin appeared to have the lowest risk rates

Summary

Introduction

We sought to analyze the FDA Adverse Event Reporting System (AERS) database in order to: (i) examine relative rates of statin side effects across muscle and tendon categories, and (ii) determine if meaningful safety differences might exist between the six main statin drugs.While others have analyzed controlled clinical trials undertaken with this class of drugs, this analysis was designed to assess links between these drugs and adverse events in large, heterogeneous ‘‘real-world’’ patient populations, by analyzing over seven-years of FDA adverse event case reports.Many studies have focused on one serious statin side effect, rhabdomyolysis. These are important in their own right, due to their greater frequency, significant effects on quality of life, and impact on statin therapy non-compliance. Our study employed both automated and manual data analysis methods in order to obtain all relevant case reports within the FDA AERS database from July 1, 2005 to March 31, 2011. Cholesterol management drugs known as statins are widely used and often well tolerated; a variety of muscle-related side effects can arise These adverse events (AEs) can have serious impact, and form a significant barrier to therapy adherence. We conducted a review of post-approval muscle and tendon AE reports in association with statin use, to assess differences within the drug class

Methods

Results

Conclusion