The cardiovascular safety of oral alitretinoin: a population‐based cohort study involving 19 513 patients exposed to oral alitretinoin

Summary Background Oral alitretinoin is a retinoid used for severe chronic hand eczema. Although caution is recommended for patients with uncontrolled dyslipidaemia or cardiovascular risk factors, the actual atherothrombotic risk has not been investigated thus far. Objectives To detect any excess of atherothrombotic events among patients exposed to alitretinoin, during treatment or in the 2 years following initiation. Methods Using the French Health Insurance database, we compared the number of patients who had an atherothrombotic event (coronary artery disease, ischaemic stroke or peripheral artery disease requiring revascularization) in the population exposed to oral alitretinoin vs. the general population of the same age, sex and baseline cardiovascular risk, using standardized morbidity ratios (SMRs). Results Between 2009 and 2017, 19 513 patients were exposed to oral alitretinoin in France. Sixty‐four (0·3%) patients had an atherothrombotic event while on alitretinoin. Patients receiving alitretinoin experienced no more atherothrombotic events than the general population: patients without cardiovascular risk factors or previous atherothrombotic events had a SMR of 0·65 [95% confidence interval (CI) 0·26–1·34] during alitretinoin treatment, and 1·21 (95% CI 0·90–1·59) in the 2 years following initiation; patients with cardiovascular risk factors or previous atherothrombotic events had a SMR of 0·82 (95% CI 0·60–1·08) during alitretinoin treatment and 0·95 (95% CI 0·82–1·09) in the 2 years following initiation. Taken separately, SMRs for each outcome did not increase either. Conclusions These data from an exhaustive nationwide population‐based study do not support an increase in the incidence of atherothrombotic events with alitretinoin use, regardless of the baseline cardiovascular risk of the patient. What is already known about this topic? Several cardiac events have been reported during alitretinoin treatment, but the risk associated with alitretinoin exposure has not been explored in a comparative study on a large scale. What does this study add? Among 19 513 patients exposed to oral alitretinoin in France, 64 (0·3%) experienced coronary artery disease, ischaemic stroke or peripheral artery disease requiring revascularization during their alitretinoin treatment, and 292 (1·5%) in the 2 years following initiation. The standardized incidence of atherothrombotic events among patients exposed to alitretinoin, compared with the general population, did n