Gabapentin and Pregabalin and Risk of Atrial Fibrillation in the Elderly: A Population-Based Cohort Study in an Electronic Prescription Database

INTRODUCTION: Gabapentin and pregabalin are widely prescribed to elderly people, but data on their pharmacokinetics, safety, and efficacy in this population are scarce. Neurological adverse effects are common. Atrial fibrillation (AF) associated with their use has been described in several case reports and case series, but the incidence is unknown. OBJECTIVE: The aim of this study was to assess the association between exposure to gabapentin or pregabalin and AF in the elderly. METHODS: Patients ≥ 65 years of age starting treatment with either gabapentin or pregabalin between January 1 and March 31, 2015, free of cardiovascular disease, and who did not receive the alternate study medications were studied. They were compared with patients who initiated treatment with an analgesic opiate or with alprazolam or diazepam. The two primary outcome variables were a first claim of an oral anticoagulant plus an antiarrhythmic drug (OAC + AA), or of an oral anticoagulant or an antiplatelet agent plus an antiarrhythmic drug (OAC/APA + AA), in the 3 months after treatment initiation. RESULTS: Compared with opiate analgesics, both gabapentin and pregabalin were associated with an increased risk of initiating OAC/APA + AA. The incidence was 6 of 668 (9.0 per 1000 patients) with gabapentin, versus 12 of 3889 (3.1 per 1000) with opiates, relative risk (RR) 2.91 (95% confidence interval [CI] 1.10–7.73), and for pregabalin it was 6 of 698 (8.6 per 1000) RR 2.79 (95% CI 1.05–7.40). The comparison with alprazolam/diazepam gave similar results. The risks did not vary by age, sex, or co-treatment with NSAIDs, and they increased with dose. CONCLUSION: In elderly patients free of cardiovascular disease, an association between new exposure to gabapentin or pregabalin and initiating treatment for AF was found. These results should be confirmed in other studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40264-018-0695-6) contains supplementary material, which is available to authorized users.