Physicians' Academy for Cardiovascular Education

Sudden death is the most common cause of death after 30 days post-NSTE-ACS

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

Literature - Berg DD, Wiviott SD, Braunwald E et al. - Eur Heart J 2018; published online ahead of print

Introduction and methods

The early consequences of non-ST-elevation acute coronary syndrome (NSTE-ACS) are well known, but the long-term risks are less well described [1]. This analysis of 14 Thrombolysis in Myocardial Infarction (TIMI) Study Group clinical trials evaluated the modes and timing of death of NSTE-ACS patients.

NSTE-ACS patients were recruited between 1989 and 2014. All 14 trials contributed ≥10 deaths and had a median follow-up duration of ≥100 days. Death was classified as cardiovascular (CV), bleeding, or non-CV/non-bleeding. CV deaths were further subdivided into specific modes of death, including sudden death (SD), recurrent myocardial infarction (MI), heart failure (including cardiogenic shock), and other CV death (including ischemic stroke, pulmonary embolism, acute aortic syndromes, and cardiac rupture), according to the definitions of the American College of Cardiology/American Heart Association [2].

Main results

Modes of death at 1 year

Modes of death during and after the first 30 days

Sudden death is the most common cause of death after 30 days post-NSTE-ACS


In a population derived from 14 clinical trials, CV events caused the majority of deaths post-NSTE-ACS. Recurrent MI represented the largest proportion of CV deaths in the first 30 days following NSTE-ACS, whereas SD was the most frequent cause of death beyond 30 days. Further research should shed light on how CV risk can be modified following NSTE-ACS to improve survival in this population.

Editorial comment

In his editorial article, Lars Wallentin [3] contrasts the results of the meta-analysis published by Berg et al., with the recent results of the SWEDEHAERT (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry that reports a 3-4-fold higher total and CV mortality at 1 (5.4% and 4.4% vs. 1.4% and 1.2%, respectively) and 12 (14.3% and 9.9% vs. 4.3% and 2.9%, respectively) months compared to the TIMI results, probably due to differences in patient selection. SWEDEHEART included all-comers with suspected or definite NSTEMI immediately on arrival while the RCTs include selected survivors at a later stage of the disease. This emphasizes concerns for the relevance of the results when testing new therapies in very selected low-risk populations. The data obtained from a selected RCT might not be representative of the complex real-life population where effects might be both smaller and larger compared to the selected RCT populations. Further, there is the risk of losing information on both efficacy and safety with testing new therapies in lower risk populations, which might have important influences on the further development and eventual approval of new therapies.

The authors conclude: ‘In order to increase the chances of clear and relevant results, all trials should be encouraged as far as possible to include the whole target population. Such a strategy is both doable and very cost-effective by performing the RCTs embedded in continuous registries rather than using the conventional approach.’


Show references

Download the slide Find this article online at Eur Heart J

Share this page with your colleagues and friends: