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

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).

Onset timing of statin‐induced musculoskeletal adverse events and concomitant drug‐associated shift in onset timing of MAEs

“…The use of the other statins is considered either moderate or low‐intensity statin therapy 1. Hoffman et al reported the following order for the relative risk of statin‐induced MAEs: rosuvastatin > atorvastatin > simvastatin > pravastatin > lovastatin 25. These indicate that the higher the HMG‐CoA reductase inhibitory activity (or the lower the IC 50 ) of a statin, the higher the relative risk of MAEs tends to be.…”

Predictors of Statin Compliance after Switching from Branded to Generic Agents among Managed-Care Beneficiaries

“…Higher potency therapy is associated with an increased rate of adverse effects, particularly myalgias, which may hinder compliance. 23,24 We found that patients receiving therapy of lower potency than when on their branded statin were also significantly less compliant with therapy compared to patients receiving equipotent doses. Although these findings are seemingly contradictory, patients who experienced adverse events and required dose decreases at the time of switching may have been less inclined to continue on statin therapy, even at lower doses.…”

Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump Inhibitors Using the FDA Adverse Event Reporting System Database

“…[11][12][13][14] It is one of the primary tools used for post-marketing surveillance and pharmacovigilance, because it is the largest, most well-known database worldwide, and it reflects the realities of clinical practice.…”