Abstract

Background: Recent findings suggest that atrial fibrillation is associated with sudden cardiac death (SCD). We examined the incidence, characteristics, and factors associated with SCD in patients with atrial fibrillation. Methods and Results: SCD was defined as witnessed death ≤60 minutes from the onset of new symptoms or unwitnessed death 1 to 24 hours after being observed alive, without another known cause of death. Predictors of SCD were examined using multivariate competing risks models. Over 2.8 years (median), 2349 patients died (40.5 per 1000 patient‐years), of which 1668 (71%) were cardiovascular deaths. SCD was the most common cause of cardiovascular death (n=749; median age 73 years; 70.6% male). Most SCD events occurred out of hospital (92.8%) and without prior symptoms (66.0%). Predictors of SCD included low ejection fraction, heart failure, and prior myocardial infarction (P<0.001 for each). Additional significant baseline predictors of SCD, but not of other causes of death, included male sex, electrocardiographic left ventricular hypertrophy, higher heart rate, nonuse of beta blockers, and use of digitalis. The latter was associated with SCD in patients with or without heart failure (adjusted hazard ratio 1.55 [95% CI 1.29–1.86] and 1.56 [95% CI 1.14–2.11], respectively; P interaction=0.73). The rate of SCD was numerically but not statistically lower with edoxaban (1.20% per year with lower dose edoxaban; 1.28% per year with higher dose edoxaban) compared with warfarin (1.40% per year). Conclusion: SCD is the most common cause of cardiovascular death in patients with atrial fibrillation and has several distinct predictors, some of which are modifiable. These findings may be considered in planning research and treatment strategies for patients with atrial fibrillation. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00781391.

Highlights

  • Characteristics, and factors associated with sudden cardiac death (SCD) in a contemporary large cohort of patients with Atrial fibrillation (AF) and the treatment interaction between edoxaban and warfarin with regard to SCD

  • Autopsy was performed in 38 patients (5.1%), and among them, chronic ischemic heart disease was the most common cause of death (52.7%)

  • The rate of SCD was higher than the rate of SCD observed in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial (n=305, 22.2% of 1371 deaths8), which might be attributed to the higher risk population included in the ENGAGE AF-TIMI 48 trial

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Summary

Methods

This study represents an analysis from the Effective Anticoagulation with Factor Xa Generation in Atrial Fibrillation– Thrombolysis In Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial. Compared with warfarin, edoxaban significantly reduced the rate of cardiovascular death.[11] Higher dose edoxaban is currently approved for clinical use in the United States, Europe, and Asia to reduce the risk of stroke and systemic embolic events in patients with AF. All multivariable analyses were adjusted for the following baseline variables: age, sex, weight, creatinine, ejection fraction

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