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.
CHEMOTHERAPY-RELATED CARDIOTOXICITY
1 The favourable haemodynamic effects of captopril in patients with congestive heart failure have been reported. 2 We have treated 25 patients with severe chronic congestive heart failure with captopril in doses of 75‐450 mg daily. Before entering the study all patients remained in New York Heart Association functional class IV despite high‐ dose diuretic and vasodilator therapy. 3 Mean cardiothoracic ratio was 60%, and all patients had a shortening fraction of 18% or less on echocardiography (normal 25 to 40%). 4 Five patients died within one month of captopril and five between four and seven months, three of whom had improved to class IIM and one to IIS before death. 5 Of the 15 survivors one was referred for a heart transplant when he had improved to class IIM. The remaining 14 patients were followed for 8‐16 months. Ten improved to New York Heart Association class I or IIS and four to class IIM or III. Diuretic requirements were decreased considerably in all 14. Side effects were common but captopril did not have to be withdrawn. Captopril is a highly effective drug in the treatment of patients with congestive heart failure refractory to currently accepted therapy.
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