Decline in Rates of Death and Heart Failure in Acute Coronary Syndromes, 1999-2006

1. Global Registry of Acute Coronary Events: GRACE Decline in Rates of Death and Heart Failure in Acute Coronary Syndromes, 1999-2006 Keith A. A. Fox, MB, ChB, FRCP; Philippe Gabriel Steg, MD; Kim A. Eagle, MD; Shaun G. Goodman, MD, MSc; Frederick A. Anderson, Jr, PhD; Christopher B. Granger, MD; Marcus D. Flather, MBBS, FRCP; Andrzej Budaj, MD, PhD; Ann Quill, MA; Joel M. Gore, MD for the GRACE Investigators Published in JAMA May 2, 2007

2. GRACE: Background • Randomized trials provide robust evidence for the impact of pharmacological and interventional treatments in patients with ST-segment elevation and non-ST-segment elevation acute coronary syndromes (NSTE ACS), resulting in changes in practice guidelines. • The extent and time course of changes in clinical practice are uncertain, however, and it is unknown whether such changes are associated with better outcomes. Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.

3. GRACE: Background (cont.) • Previous studies have documented discrepancies between guideline recommendations and clinical practice; thus, there is a clinical priority to determine the extent to which evidence is applied in practice, whether this is changing over time, and whether such changes are associated with improved outcomes. • The aim of this study was to determine whether changes in hospital management of patients with ST-segment elevation of myocardial infarction (STEMI) and NSTE ACS are associated with improvements in clinical outcome. Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.

4. GRACE: Study Design The Global Registry of Acute Coronary Events (GRACE), a multinational cohort study, enrolled and followed up 44,372 patients ≥18 years and with an ACS in 113 hospitals in 14 countries NSTE ACS n=27,558 STEMI n=16,814 Follow-up for approximately 6 mos. after hospital discharge • Primary Endpoint: In-hospital death, recurrent myocardial infarction, heart failure, stroke, and cardiogenic shock Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.

5. GRACE: Baseline Characteristics • Patients with STEMI were more often male (72% vs 65%) and were slightly younger than those with NSTE ACS (65 vs 68 years) . • Patients with NSTE ACS had a more complex medical history than patients with STEMI. • Patients with NSTE ACS were less likely to be current smokers (21% vs 36%) and more likely to be past smokers (32% vs 23%). Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.

6. GRACE: Changes in Therapy for STEMI patients Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.

7. GRACE: Changes in Therapy for STEMI patients (cont.) • Use of pharmacological medication increased over the study period. • Use of pharmacological reperfusions ↓ by 22 percentage points, whereas the rate of primary PCI ↑ by 37 percentage points over the same interval. • Proportion of patients with STEMI who did not receive pharmacological reperfusion therapy or primary rescue or facilitated PCI declined by 5.5 percentage points. Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.

8. GRACE: Changes in Therapy for NSTE ACS patients Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.

9. GRACE: Changes in Therapy for NSTE ACS patients (cont.) • Use of pharmacological medication increased over the study period. • There was a modest decrease in the use of coronary artery bypass graft (CABG) surgery of 1.7 percentage points. • The frequency of angiography increased markedly by 21 percentage points, while the use of PCI increased substantially by 18 percentage points. Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.

10. GRACE: Outcome Measures over Time Changes in Clinical Outcomes for STEMI Patients • Hospital deaths decreased by 3.9% (95% CI, -5.3 to -1.9) and the rate of in-hospital congestive heart failure (CHF) or pulmonary edema declined by 9.0% (95% CI, -12 to -6). p < .001 Death or CHF (%) p < .001 n = 992 n = 1351 n = 993 n = 1335

11. GRACE: Outcome Measures over Time Changes in Clinical Outcomes for NSTE ACS Patients • Risk-adjusted hospital deaths declined by 0.7 percentage points (95% CI, -1.7 to 0.3 in NSTE ACS patients. • The rate of congestive heart failure and pulmonary edema decreased by 6.5% (95% CI, -8.4 to -4.7). Death or CHF (%) p <.001 p = .02 n = 2228 n = 2213 n = 1564 n =1566

12. GRACE: 6-month Outcomes Death Outcomes for STEMI and NSTE ACS patients at 6-month follow-up • The rate of death between hospital discharge and 6-month follow-up decreased by 1.6% (95% CI, -3.0 to -0.1) in NSTE ACS patients. Death or CHF (%) p = .64 p = .04 n = 1099 n = 1942 n = 998 n =620

13. GRACE: Limitations • The participating clusters reflect regional practices and outcomes but do not necessarily reflect practice for specific countries. • Participating hospitals are sent feedback on a 6-month basis, so it cannot be determined whether improvements in adherence to evidence-based medication are taking place nationwide or are limited to participating sites. Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.

14. GRACE: Limitations (cont.) • Increasing use of troponin measurement throughout the study may have led to underestimation of the detection of small reinfarctions if troponin was already elevated at presentation and if the patient did not evolve new electrocardiographic changes of MI. Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.

15. GRACE: Summary • In this multinational observational study, improvements in the management of patients with ACS were associated with significant reductions in the rates of new heart failure and mortality and in rates of stroke and MI at 6 months. • This study population is the first demonstration of significant reductions observed in hospital rates of new heart failure in ACS patients, over time, and of reductions in mortality. Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.