Sudden Cardiac Death in Patients With Atrial Fibrillation: Insights From the ENGAGE AF-TIMI 48 Trial

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; Pinteraction=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.

Keywords: atrial fibrillation; sudden cardiac death.

© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1

Causes of deaths (A) and their cumulative incidence (B) in the ENGAGE AF‐TIMI 48 trial. Deaths are categorized as SCD, other CVD, and non‐CVD. *Other CVD: atherosclerotic vascular disease excluding coronary (n=25); directly related to coronary revascularization (n=12); dysrhythmia (n=51); pulmonary embolism (n=17); systemic embolic event (n=8); unknown (n=146). CVD indicates cardiovascular death; HF, heart failure; SCD, sudden cardiac death.

Figure 2

Characterization of sudden cardiac death events by the location of death, whether it was witnessed, and whether an arrhythmia was documented. AF indicates atrial fibrillation; PEA, pulseless electrical activity; SCD, sudden cardiac death; VF, ventricular fibrillation; VT, ventricular tachycardia.

Figure 3

SCD stratified by the use of digitalis and BBs at baseline. The risk of SCD was the highest among patients who were treated with digitalis and were not treated with BBs at baseline (red line). Adjustment variables: age, sex, weight, creatinine, ejection fraction <50%, hypertension, diabetes mellitus, smoking, mitral valve disease, aortic valve disease, peripheral arterial disease, prior stroke or transient ischemic attack, prior myocardial infarction, New York Heart Association class, type of atrial fibrillation, prior electrical cardioversion, race, previous use of vitamin K antagonists for ≥60 days, class II antiarrhythmics, class III antiarrhythmics, digitalis use, left ventricular hypertrophy per ECG, heart rate, randomization group, lipid‐lowering drugs, renin–angiotensin–aldosterone system inhibitors. Adj HR indicates adjusted hazard ratio; BB, beta blocker; SCD, sudden cardiac death.

Figure 4

Kaplan–Meier curves of sudden cardiac death by treatment arm. HR indicates hazard ratio.