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  • Clinical Research
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Time course of events in acute coronary syndromes: implications for clinical practice from the GRACE registry

Abstract

Background The time course of events after acute coronary syndromes might influence the timing and duration of therapeutic interventions. We investigated the impact of risk status and ST-segment category at presentation.

Methods The timing of death, reinfarction, stroke and major bleeding within 6 months of acute coronary syndromes was determined in 46,829 patients enrolled in the Global Registry of Acute Coronary Events (GRACE). Acute coronary syndromes were classified by elevation (n = 17,668), depression (n = 8,542), or neither (n = 20,619) in the ST segment. GRACE risk scores and hazard ratios (HR) were determined for three time periods: 0–4, 5–15 and 16–180 days.

Results ST-segment elevation was associated with a higher early risk of death than was ST-segment depression (0–4 days, HR 1.89, 95% CI 1.60–2.24 versus 5–15 days, HR 1.26, 95% CI 1.05–1.50), but after 15 days the risk was reversed (16–180 days, HR 0.85, 95% CI 0.75–0.97). Throughout the study, patients with ST-segment deviation had a higher mortality risk than those without. Within each ST category, the highest GRACE risk scores were associated with a 10–40-fold greater risk of death than the lowest scores (all categories P <0.0001). Most deaths occurred after day 4 (57%, 74%, and 78% for ST-segment elevation, depression and neither, respectively).

Conclusion The timing of events after acute coronary syndromes was affected by ST category and influenced by GRACE risk score within each electrocardiographic category of acute coronary syndromes. Risk stratification should, therefore, include multiple risk factors rather than ST shift alone.

Key Points

  • The temporal distribution of postpresentation events (death, infarction, reinfarction, new stroke, and major bleed) in patients hospitalized for an acute coronary syndrome (ACS) varies according to ST category but is powerfully influenced by the GRACE risk score

  • Our data demonstrate a 10–40-fold range of death within each category of ST deviation (ST elevation, ST depression, or no ST deviation); thus, ST segment deviation alone is an inadequate basis for risk prediction

  • Within the first 15 days of presentation with ACS, patients with ST elevation at initial presentation are at greatest risk of death

  • In contrast, in the postdischarge period, there is a higher risk of death in patients with ST depression at initial presentation

  • Almost two-thirds of all events in the first 6 months after hospital presentation occur in the period beyond the first 4 days (66% of deaths, 59% of reinfarctions)

  • For those with ST depression at initial presentation, three-quarters of all the deaths in the first 6 months occur beyond the median period of hospitalization (beyond 4 days)

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Figure 1: Empirical hazard function for mortality and Kaplan–Meier curves showing cumulative incidence of death in patients presenting with acute coronary syndromes.
Figure 2: Event rates by time interval in patients presenting with acute coronary syndromes.

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Acknowledgements

This research was supported by an unrestricted grant from Sanofi-Aventis, Paris, France. We thank the physicians and nurses participating in GRACE. Further information about the project, along with the complete list of participants, can be found at http://www.outcomes.org/grace. The authors are grateful to S Rushton-Smith, who provided editorial support in the preparation of this paper. GRACE is supported by an unrestricted educational grant from Sanofi-Aventis to the Center for Outcomes Research, University of Massachusetts Medical School. Sanofi-Aventis had no involvement in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

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Correspondence to Keith AA Fox.

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Competing interests

KAA Fox is a consultant for and is funded by GlaxoSmithKline and Sanofi-Aventis. He is also funded by Merck.

FA Anderson is funded by Sanofi-Aventis, Scios and The Medicines Company. He is a consultant for GlaxoSmithKline.

PG Steg is funded by Sanofi-Aventis. He is a consultant for Astellas, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Endotis Pharma, GlaxoSmithKline, Medtronic, Merck, Nycomed, Sanofi-Aventis, Servier, Takeda and The Medicines Company.

JM Gore is funded by Sanofi-Aventis.

The other authors declared no competing interests.

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Fox, K., Anderson Jr, F., Goodman, S. et al. Time course of events in acute coronary syndromes: implications for clinical practice from the GRACE registry. Nat Rev Cardiol 5, 580–589 (2008). https://doi.org/10.1038/ncpcardio1302

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