In a new study, Dr Pierluigi Tricoci of the Duke Clinical Research Institute, Durham, North Carolina, and colleagues assessed the cumulative incidence of sudden cardiac death (SCD) during long-term follow-up after non-ST-segment elevation acute coronary syndrome (NSTE ACS; a type of heart attack or unstable angina with certain findings on an electrocardiogram), and developed a risk model and risk score for SCD after NSTE ACS.
Improving management strategies to prevent SCD after an ACS requires an understanding of a patient’s individual absolute risk. However, algorithms to assess individual patients’ risks have not been developed. For this study, the researchers merged individual data from 4 multinational randomised clinical trials among patients presenting with an ACS. The cumulative incidence of SCD and cardiovascular death was examined according to time after NSTE ACS. 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.
Of the initial 48,286 patients in the analysis, 37,555 patients were enrolled after NSTE ACS. Among these, 2,109 deaths occurred after a median follow-up of 12.1 months. Of 1,640 cardiovascular deaths, 513 (31 percent) were SCD. At 6, 18, and 30 months, the cumulative incidence estimates of SCD were 0.8%, 1.7%, and 2.4%, respectively. The researchers found that certain clinical variables were significantly associated with SCD.
“We report 3 main findings of this analysis. First, in the current NSTE ACS therapeutic era, SCD occurs relatively infrequently at a rate of approximately 1% per year, yet it accounts for one-third of cardiovascular deaths observed during follow-up. Sudden cardiac death accrues continuously over time; its incidence does not plateau even after the first year from the acute event. Second, an SCD risk model consisting of commonly collected clinical variables, from which we derived a more user-friendly risk score, can be used for risk stratification of SCD and identification of patients who are at higher risk for SCD. Third, recurrent events subsequent to the initial ACS presentation, in particular recurrent (heart attack) and rehospitalisation, are associated with the risk for subsequent SCD,” the authors write.
“Future research is needed to assess the implementation of drug¬ or device-based strategies that may reduce the risk for SCD in high-risk patients after NSTE ACS.”
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.