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. 2018 Nov 7;39(42):3810-3820.
doi: 10.1093/eurheartj/ehy556.

Modes and timing of death in 66 252 patients with non-ST-segment elevation acute coronary syndromes enrolled in 14 TIMI trials

David D Berg  1 , Stephen D Wiviott  1 , Eugene Braunwald  1 , Jianping Guo  1 , KyungAh Im  1 , Amir Kashani  2 , C Michael Gibson  3 , Christopher P Cannon  4 , David A Morrow  1 , Deepak L Bhatt  4 , Jessica L Mega  5 , Michelle L O'Donoghue  1 , Elliott M Antman  1 , L Kristin Newby  6 , Marc S Sabatine  1 , Robert P Giugliano  1
Affiliations

Modes and timing of death in 66 252 patients with non-ST-segment elevation acute coronary syndromes enrolled in 14 TIMI trials

David D Berg et al. Eur Heart J. .

Abstract

Aims: Although presenting features and early sequelae of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are well described, less is known about longer-term risks and modes of death. The purpose of this study was to characterize modes of death following NSTE-ACS in clinical trial populations.

Methods and results: We evaluated 66 252 patients with NSTE-ACS enrolled in 14 Thrombolysis in Myocardial Infarction (TIMI) trials, examining baseline characteristics and modes and timing of death. Of the 66 252 patients followed for a median of 372 (interquartile range 218-521) days, 3147 (4.8%) died by the time of last follow-up. Of the 2606 patients (82.8%) with known modes of death, 75.1% were related to a cardiovascular (CV) event, 3.0% were related to a bleeding event (including intracranial haemorrhage), and 21.8% were related to a non-CV/non-bleeding event. The most common modes of CV death were sudden death (SD) and recurrent myocardial infarction (MI) (36.4% and 23.4%, respectively, of CV deaths). The proportion of CV deaths related to recurrent MI was higher in the first 30 days than it was after 30 days following NSTE-ACS (30.6% vs. 18.7%), whereas the proportion of SD was lower in the first 30 days than after 30 days (21.6% vs. 46.2%).

Conclusion: Sudden death represents the largest proportion of CV deaths after 30 days among patients enrolled in CV clinical trials with NSTE-ACS. Further investigations aimed at defining the epidemiology of SD and developing specific therapies and management approaches to reduce SD following NSTE-ACS may be critical to reducing late mortality.

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Figures

Figure 1
Figure 1
Cumulative mortality of non-ST-segment elevation acute coronary syndrome patients in the merged clinical trial database. Cumulative mortality rates were calculated using the complement of Kaplan–Meier survival estimates. The numbers below the x-axis indicate the number of patients alive and still being followed at the corresponding time. The 95% confidence interval is indicated with dashed lines.
Figure 2
Figure 2
Landmark analysis of the cumulative incidence of modes of death starting at 30 days following the index non-ST-segment elevation acute coronary syndrome event. The cumulative incidence of each (A) general class of death and (B) specific cardiovascular mode of death starting at 30 days following non-ST-segment elevation acute coronary syndrome is shown through 12 months. Point estimates are provided at 12 months.
Take home figure
Take home figure
Cumulative incidence of modes of death. The cumulative incidence of each (A) general class of death and (B) specific cardiovascular mode of death is shown over the first year following trial enrollment for non-ST-segment elevation acute coronary syndrome. The number of patients at-risk is shown below the x-axis and accounts for the presence of competing risks. Point estimates are provided at 12 months.
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