Oral bisphosphonates and risk of ischemic stroke: a case–control study

Summary Bisphosphonates have been associated with an increased risk of atrial fibrillation and may thus be associated with an increased risk of ischemic stroke. This would have substantial clinical and public health implications. We found no evidence of an association between bisphosphonate use and risk of ischemic stroke. Introduction Bisphosphonates have been associated with an increased risk of atrial fibrillation in some studies and may be associated with an increased risk of ischemic stroke. However, data regarding these possibilities are limited. Methods We conducted a population-based case–control study of 6,257 female cases of ischemic stroke and 31,285 age- and gender-matched population controls. Data on bisphosphonate use, other medication use, comorbidity, and ischemic stroke were obtained from medical databases. Current bisphosphonate use was defined as at least one redeemed prescription within 90 days before diagnosis/ index date. We estimated the odds ratio (OR) of ischemic stroke among users and nonusers of bisphosphonates using conditional logistic regression, controlling for potential confounding factors. Results One hundred eighty-two (2.9%) cases and 901 (2.9%) controls were current users of bisphosphonates. Etidronate and alendronate were prescribed with similar frequency among cases and controls. The adjusted OR of ischemic stroke for bisphosphonate users compared with nonusers was 0.97 (95%confidence interval [CI], 0.82–1.15). New and continuing bisphosphonate users had adjusted ORs for ischemic stroke of 1.16 (95% CI, 0.69–1.96) and 0.97 (95% CI, 0.81–1.16), respectively. Excluding patients with known atrial fibrillation/flutter yielded an OR of 1.00 (95% CI, 0.85–1.19). The OR for ischemic stroke was 0.59 (95% CI, 0.32–1.09) among patients with a history of previous hospitalization for cardiovascular disease and 1.07 (95% CI, 0.88–1.18) among those without (P<0.001). The OR for former users was 1.23 (95% CI, 1.01–1.49). Conclusion We found no evidence of an association of oral bisphosphonate use with the risk of ischemic stroke.