Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study)
Keith A A Fox1, Kathryn F Carruthers, Donald R Dunbar
1Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK. K.A.A.Fox@ed.ac.uk
Insights
The Global Registry of Acute Coronary Events (GRACE) risk score accurately predicts 5-year mortality and death/myocardial infarction (MI) in acute coronary syndrome (ACS) patients. Long-term outcomes for non-ST elevation MI and unstable angina are as severe as for STEMI, highlighting under-recognized risks.
Area of Science:
- Cardiology
- Clinical Research
- Public Health
Background:
- Acute coronary syndrome (ACS) encompasses ST-segment elevation myocardial infarction (STEMI), non-STEMI, and unstable angina (UA).
- Long-term outcomes and mortality prediction in ACS patients require further definition.
- The Global Registry of Acute Coronary Events (GRACE) risk score is utilized for risk stratification.
Purpose of the Study:
- To determine the 5-year prognosis for patients with various types of ACS.
- To validate the predictive accuracy of the GRACE risk score for long-term mortality and death/myocardial infarction (MI) events.
Main Methods:
- Prospective, longitudinal study of ACS patients across UK and Belgian centers.
- Median follow-up of 5 years, recording deaths, cardiovascular deaths (CVDs), MIs, strokes, and revascularizations.
- Statistical analysis using Cox proportional hazards models and landmark analysis to assess GRACE score predictive performance.
Main Results:
- The GRACE risk score demonstrated strong predictive capability for 5-year all-cause death (C-statistic 0.77), CVD (C-statistic 0.75), and CVD/MI (C-statistic 0.70).
- Patients in intermediate and high-risk GRACE strata exhibited significantly higher risks of death compared to the low-risk group.
- Cumulative mortality rates at 5 years were comparable between STEMI, non-STEMI, and UA, with a substantial proportion of deaths occurring post-discharge, particularly for non-STEMI and UA.
Conclusions:
- The GRACE risk score is a reliable predictor of early and 5-year adverse outcomes, including death and CVD/MI.
- Morbidity and mortality at 5 years are substantial and similar across STEMI, non-STEMI, and UA, indicating under-recognized long-term risks in non-ST-elevation ACS.
- Novel strategies are needed to mitigate the significant long-term risks associated with ACS.
Aim:
To define the long-term outcome of patients presenting with acute coronary syndrome [ST-segment elevation myocardial infarction (STEMI), and non-STEMI and unstable angina acute coronary syndrome (ACS) without biomarker elevation] and to test the hypothesis that the GRACE (Global Registry of Acute Coronary Events) risk score predicts mortality and death/MI at 5 years.
Methods And Results:
In the GRACE long-term study, UK and Belgian centres prospectively recruited and followed ACS patients for a median of 5 years (1797 days). Primary outcome events: deaths, cardiovascular deaths (CVDs) and MIs. Secondary events: stroke and re-hospitalization for ACS. There were 736 deaths, 19.8% (482 CVDs, 13%) and 347 (9.3%) MIs (>24 h), 261 strokes (7.7%), and 452 (17%) subsequent revascularizations. Rehospitalization was common: average 1.6 per patient; 31.2% had >1 admission, 9.2% had 5+ admissions. These events were despite high rates of guideline indicated therapies. The GRACE score was highly predictive of all-cause death, CVD, and CVD/MI at 5 years (death: χ(2) likelihood ratio 632; Wald 709.9, P< 0.0001, C-statistic 0.77; for CVD C-statistic 0.75, P < 0.0001; CVD/MI C-statistic 0.70, P < 0.0001). Compared with the low-risk GRACE stratum (ESC Guideline criteria), those with intermediate [hazard ratio (HR) 2.14, 95% CI 1.63, 2.81] and those with high-risk (HR 6.36, 95% CI 4.95, 8.16) had two- and six-fold higher risk of later death (Cox proportional hazard). A landmark analysis after 6 months confirmed that the GRACE score predicted long-term death (χ(2) likelihood ratio 265.4; Wald 289.5, P < 0.0001). Although in-hospital rates of death and MI are higher following STEMI, the cumulative rates of death (and CVD) were not different, by class of ACS, over the duration of follow-up (Wilcoxon = 1.5597, df = 1, P = 0.21). At 5 years after STEMI 269/1403 (19%) died; after non-STEMI 262/1170 (22%) after unstable angina (UA) 149/850 (17%). Two-thirds (68%) of STEMI deaths occurred after initial hospital discharge, but this was 86% for non-STEMI and 97% for UA.
Conclusion:
The GRACE risk score predicts early and 5 year death and CVD/MI. Five year morbidity and mortality are as high in patients following non-ST MI and UA as seen following STEMI. Their morbidity burden is high (MI, stroke, readmissions) and the substantial late mortality in non-STE ACS is under-recognized. The findings highlight the importance of pursuing novel approaches to diminish long-term risk.
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