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.

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We prospectively studied perioperative changes of renal function in 12 previously normal patients (plasma creatinine < 1.5 mg/dL) scheduled for elective coronary surgery. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured with inulin and 125I-hippuran clearances before induction of anesthesia, before cardiopulmonary bypass (CPB), during hypo- and normothermic CPB, after sternal closure, and 1 h postoperatively. Renal and systemic vascular resistances were calculated. Urinary N-acetyl-beta-D-glucosaminidase (NAG) and plasma and urine electrolytes were measured, and free water, osmolal, and creatinine clearances, and fractional excretion of sodium and potassium were calculated before and after surgery. 125I-hippuran clearance was lower than normal in all patients before surgery. During hypothermic CPB, ERPF increased significantly (from 261 +/- 107 to 413 +/- 261 mL/min) and returned toward baseline values during normothermia. GFR was normal before and after surgery and decreased nonsignificantly during CPB. Filtration fraction was above normal before surgery and decreased significantly during CPB (0.38 +/- 0.09 to 0.18 +/- 0.06). Renal vascular resistance (RVR) was high before surgery and further increased after sternotomy (from 18,086 +/- 6849 to 30,070 +/- 24,427 dynes.s.cm-5), decreasing during CPB to 13,9647 +/- 14,662 dynes.s.cm-5. Urine NAG, creatinine, and free water clearances were normal in all patients both pre- and postoperatively. Osmolal clearance and fractional excretion of sodium increased postoperatively from 1.54 +/- 0.06 to 12.47 4/- 11.37 mL/min, and from 0.44 +/- 0.3 to 6.07 +/- 6.27, respectively. We conclude that renal function does not seem to be adversely affected by CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

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Two protective interventions were compared in patients undergoing heart surgery to prevent deterioration of renal function; these were dopamine infusion throughout the operation and phenylephrine infusion during cardiopulmonary bypass. We found clinically relevant differences only during surgery before cardiopulmonary bypass.