Lipid-lowering drugs and the risk of cataract: An Observational Post Marketing Study

Abstract

The risk of cataracts (C) associated to lipid-lowering drugs (LLD) is discussed. Following early warnings in animal models, several clinical and observational studies led to conflicting results. We assessed in real life the association between LLD and C using the WHO individual case safety reports database, VigiBase®, including reports from over 130 countries worldwide. We performed a disproportionality analysis with all reports between 1/1/1988 and 31/12/2018 to measure the reporting risk of “cataract” in patients ≥ 45 years. Primary analysis compared LLD users to non-users. We performed 2 sensitivity analyses: (1) exclusion of reports with 2 LLD associated, (2) exclusion of patients with antidiabetics and glucocorticoids, known to induce C. Finally, we investigated the drugs more at risk in each class. We identified 14,664 reports of cataract (3,049 in users, 66% women, 66 ± 20 y). The most frequently involved LLD were statins [84%, atorvastatin (n = 1.016), simvastatin (626), rosuvastatin (392), lovastatin (343), pravastatin (268)] followed by fibrates [5.7%, fenofibrate (117), gemfibrozil (56)], nicotinic acid (3%), bile acid sequestrants (2%), herbal cholesterol and triglyceride reducers (2%) and others (15%). LLD users were associated to a greater C risk than non-users ROR: 2.47 (95%CI: 2.37–2.57). This risk was also found for statins in general, fibrates, bile sequestrants, nicotinic acid, herbal drugs and others (ezetimibe, PCSK9 inhibitors). Similar trends were observed in sensitivity analyses. The most important risk was found for statins with lovastatin followed by pravastatin and atorvastatin and for fibrates with fenofibrate. Using a large real life database (18.5 million reports), we found for the first time a signal of cataract for all LLD, i.e. not only statins but also fibrates and other classes suggesting that a decrease in cholesterol is involved in the pathophysiology of C with LLD.