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Original Investigation
April 2016

Sudden Cardiac Death After Non–ST-Segment Elevation Acute Coronary Syndrome

Author Affiliations
  • 1Veterans Affairs Eastern Colorado and Health Care System, Denver
  • 2Department of Medicine, University of Colorado School of Medicine, Aurora
  • 3Duke Clinical Research Institute, Durham, North Carolina
  • 4Department of Medicine, Duke University School of Medicine, Duke Clinical Research Institute, Durham, North Carolina
  • 5Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina
  • 6Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
  • 7Division of Cardiology, University of Alberta, Edmonton, Canada
  • 8Department of Medicine, Stanford University, Stanford, California
  • 9Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand
  • 10Department of Cardiology, University of Leuven, Leuven, Belgium
  • 11South Australian Health and Medical Research Institute, Flinders University and Medical Centre, Adelaide, Australia
  • 12Gill Heart Institute and Division of Cardiovascular Medicine, University of Kentucky, Lexington
JAMA Cardiol. 2016;1(1):73-79. doi:10.1001/jamacardio.2015.0359
Abstract

Importance  In the current therapeutic era, the risk for sudden cardiac death (SCD) after non–ST-segment elevation acute coronary syndrome (NSTE ACS) has not been characterized completely.

Objective  To determine the cumulative incidence of SCD during long-term follow-up after NSTE ACS, to develop a risk model and risk score for SCD after NSTE ACS, and to assess the association between recurrent events after the initial ACS presentation and the risk for SCD.

Design, Setting, and Participants  This pooled cohort analysis merged individual data from 48 286 participants in 4 trials: the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2), Study of Platelet Inhibition and Patient Outcomes (PLATO), Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER), and Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trials. The cumulative incidence of SCD and cardiovascular death was examined according to time after NSTE ACS. Using competing risk and Cox proportional hazards models, clinical factors at baseline and after the index event that were associated with SCD after NSTE ACS were identified. Baseline factors were used to develop a risk model. Data were analyzed from January 2, 2014, to December 11, 2015.

Main Outcomes and Measures  Sudden cardiac death.

Results  Of the initial 48 286 patients, 37 555 patients were enrolled after NSTE ACS (67.4% men; 32.6% women; median [interquartile range] age, 65 [57-72] years). Among these, 2109 deaths occurred after a median follow-up of 12.1 months. Of 1640 cardiovascular deaths, 513 (31.3%) were SCD. At 6, 18, and 30 months, the cumulative incidence estimates of SCD were 0.79%, 1.65%, and 2.37%, respectively. Reduced left ventricular ejection fraction, older age, diabetes mellitus, lower estimated glomerular filtration rate, higher heart rate, prior myocardial infarction, peripheral artery disease, Asian race, male sex, and high Killip class were significantly associated with SCD. A model developed to calculate the risk for SCD in trials with systematic collection of left ventricular ejection fraction had a C index of 0.77. An integer-based score was developed from this model and yielded a calculated SCD probability ranging from 0.1% to 56.7% (C statistic, 0.75). In a multivariable model that included time-dependent clinical events occurring after the index hospitalization for ACS, SCD was associated with recurrent myocardial infarction (hazard ratio [HR], 2.95; 95% CI, 2.29-3.80; P < .001) and any hospitalization (HR, 2.45; 95% CI, 1.98-3.03; P < .001), whereas coronary revascularization had a negative relationship with SCD (HR, 0.75; 95% CI, 0.58-0.98; P = .03).

Conclusions and Relevance  In the current therapeutic era, SCD accounts for about one-third of cardiovascular deaths after NSTE ACS. Risk stratification can be performed with good accuracy using commonly collected clinical variables. Clinical events occurring after the index hospitalization are underappreciated but important risk factors.

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