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

Abstract

BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 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 classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 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 with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Atrial Fibrillation and Hypertension

“…18 Of note, higher diastolic BP was associated with lower all-cause mortality (HR, 0.92; 95% CI, 0.87-0.98). 19 Thus, the available data do not advocate lowering of BP in AF patients below the recommended targets. Furthermore, both AF and hypertension are often accompanied by coronary heart disease, 20 The presence of LV hypertrophy and increased arterial stiffness in hypertensive patients have been associated with higher incidence of AF.…”

Model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients

“…38,39 These are well-known risk factors for fatal events in AF patients, which would explain the higher mortality rate in patients receiving the reduced dose. 40,41 In the Danish study, no distinct difference was observed between the 2 dose groups in the total incidence of stroke/SE/transient ischemic attack (6.0%/y vs 6.0%/y) and any bleeding (15 mg, 4.6%/y vs 20 mg, 4.2%/y). 38 Therefore, it is unlikely that a dose reduction was directly associated with the increased mortality in this population.…”

Characteristics and outcomes of adults with chronic obstructive pulmonary disease and atrial fibrillation

“…As in our study, COPD was an independent risk factor for CV mortality among patients with AF enrolled in EORP-AF. COPD was also an important risk factor for mortality in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial7 and in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation study 6. In contrast to clinical trials, in which patients with higher comorbidity burden may be under-represented, the prevalence of COPD in ORBIT-AF was relatively higher at 16%.…”

“…In the general population, patients with COPD are at higher risk of cardiovascular (CV) morbidity and mortality than patients without COPD 4 5. Among patients with AF, COPD has been associated with all-cause6 and CV mortality7 in clinical trials, independent of other known risk factors. COPD is also associated with higher risk of major bleeding among patients with AF treated with anticoagulants in the context of clinical trials 8.…”