Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: Data From ROCKET AF

Background-—Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factorsfor all-cause mortality may guide interventions.Methods and Results-—In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism forPrevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation wererandomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identifiedfactors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intentionto-treat population. The median age was 73 years, and the mean CHADS2 score was 3.5. Over 1.9 years of median follow-up,1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classifieddeaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significantdifference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated withhigher all-cause mortality. Multiple additional characteristics were independently associated with higher mortality, withdecreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetesbeing among the most strongly associated (model C-index 0.677).Conclusions-—In a large population of patients anticoagulated for nonvalvular atrial fibrillation, 7 in 10 deaths werecardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention andtreatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.