Erol, Çetin

Background Patients with atrial fibrillation ( AF ) and hypertension are at high risk for stroke. Previous studies have shown elevated risk of stroke in patients with AF who have a history of hypertension (regardless of blood pressure [ BP ] control) and in patients with elevated BP . We assessed the association of hypertension and BP control on clinical outcomes. Methods and Results In ARISTOTLE (n=18 201), BP was evaluated as history of hypertension requiring treatment and elevated BP (systolic ≥140 and/or diastolic ≥90 mm Hg) at study entry and any point during the trial. Hazard ratios ( HR s) were derived from Cox proportional hazards models including BP as a time‐dependent covariate. A total of 15 916 (87.5%) patients had a history of hypertension requiring treatment. In patients with elevated BP measurement at any point during the trial, the rate of stroke or systemic embolism was significantly higher ( HR , 1.53; 95% confidence interval [ CI ], 1.25–1.86), as was hemorrhagic stroke ( HR 1.85; 95% CI , 1.26–2.72) and ischemic stroke ( HR , 1.50; 95% CI , 1.18–1.90). Rates of major bleeding were lower in patients with a history of hypertension ( HR , 0.80; 95% CI , 0.66–0.98) and nonsignificantly lower in patients with elevated BP at study entry ( HR , 0.89; 95% CI , 0.77–1.03). The benefit of apixaban versus warfarin on preventing stroke or systemic embolism was consistent among patients with and without a history of hypertension ( P interaction=0.27), BP control at baseline ( P interaction=0.43), and BP control during the trial ( P interaction=0.97). Conclusions High BP measurement at any point during the trial was independently associated with a substantially higher risk of stroke or systemic embolism. These results strongly support efforts to treat elevated BP as an important strategy to optimally lower risk of stroke in patients with AF . Clinical Trial Registration URL : https://ClinicalTrials.gov/ . Unique identifier: NCT 00412984.

Background— Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves. Methods and Results— We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51–0.97 and HR, 0.84; 95%, CI 0.67–1.04; interaction P =0.38), causing less major bleeding (HR, 0.79; 95% CI, 0.61–1.04 and HR, 0.65; 95% CI, 0.55–0.77; interaction P =0.23), and reducing mortality (HR, 1.01; 95% CI, 0.84–1.22 and HR, 0.84; 95% CI, 0.73–0.96; interaction P =0.10). Conclusions— More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00412984.