Pharmacovigilance Analysis of Cataract and Cataract Operation Adverse Event Reports Submitted for Lipid-Lowering Drugs

INTRODUCTION: There has been concerns about the association between statins and cataract risk. This study detects and clarifies signals of cataract and cataract operation associated with lipid-lowering drugs (LLD), including statins, from real-world data of postmarketing adverse event reports.

METHODS: A retrospective pharmacovigilance analysis of adverse events submitted to the US FDA Adverse Event Reporting System from October 1997 through September 2012 was conducted. Multi-item Gamma Poisson Shrinker data mining algorithm is applied to detect signals of cataract and cataract operation in FAERS; Empirical Bayes Geometric Mean (EBGM) values and corresponding 95% confidence intervals (EB05-EB95) are estimated for drug-event associations. Estimates with EB05≥2 are significant disproportional reporting of cataract and cataract operation for LLD. The Preferred Term hierarchy of Medical Dictionary for Regulatory Activities is used to define cataract and cataract operation, and generic name of the reported drug is used to define LLD exposure.

RESULTS: A total of 1,195 cataract and 99 cataract operation reports were submitted for LLD (respectively, 94% and 95% of these reports were for statins). Most of cataract reports were for lovastatin (n=399) and most of cataract operation reports were for atorvastatin (n=68). Among LLD, cataract signal was detected for statins (EBGM=3.64, EB05-EB95=3.18-4.20). Among statins, lovastatin was associated with the strongest signal of cataract formation (EBGM=12.8, EB05-EB95=11.8-14.0), followed by pravastatin (EBGM=3.82, EB05-EB95=3.21-4.53) and atorvastatin (EBGM=2.95, EB05-EB95=2.70-3.21). No cataract operation signal was detected, including for statins (EBGM=1.52, EB05-EB95=1.08-2.36); however, cataract operation signals were detected for rosuvastatin (EBGM=3.82, EB05-EB95=3.21-4.53) and atorvastatin (EBGM=3.33, EB05-EB95=2.72-4.05). Disproportional reporting of cataract with EB05>1 was found for simvastatin (EB05=1.66), fluvastatin (EB05=1.34) and gemfibrozil (EB05=1.32).

CONCLUSIONS: Antilipemic treatment with statins may be associated with an increased risk of cataract development or operation. Statin users with risk factors for cataract formation should have routine ophthalmic examination for lenticular opacity, and alternative LLD should be used in high-risk patients.