Effect of Addition of a Statin to Warfarin on Thromboembolic Events in Japanese Patients With Nonvalvular Atrial Fibrillation and Diabetes Mellitus

Abstract Statins have been shown to decrease stroke risk in patients with cardiovascular risk factors, but not to prevent recurrence of ischemic stroke in patients with atrial fibrillation (AF). The present subanalysis aimed to clarify the efficacy of combined use of warfarin and statins in nonvalvular AF (NVAF) patients with coronary artery disease (CAD), diabetes mellitus (DM) or hypertension. The effects of adding statins to warfarin were compared with those of warfarin alone in NVAF patients with the data set of J-RHYTHM Registry, a prospective, observational study with a 2-year follow-up. End points included thromboembolism, major hemorrhage, all-cause mortality and cardiovascular mortality. Of 7406 patients with NVAF and follow-up data, 6404 patients received warfarin at baseline. Of these, 1605 patients also received a statin. Patients in the warfarin plus statin group showed significantly lower all-cause mortality as compared to patients on warfarin alone (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.38-0.87, p=0.0089), although thromboembolic event rates did not differ significantly (HR 0.73, 95% CI 0.44-1.20, p=0.21). In contrast, in 1223 patients with DM, the warfarin plus statin group showed significantly lower thromboembolic event rates than the warfarin alone group (HR 0.33, 95% CI 0.11-0.96, p=0.041). Interestingly, in patients with CAD or with hypertension the addition of statin to warfarin did not decrease the frequency of thromboembolic events. In conclusion, in Japanese NVAF patients with DM, a combination of warfarin and a statin could be clinically beneficial for preventing thromboembolic events.