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

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

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; Keith A. A. Fox, MB, ChB, FRCP; Philippe Gabriel Steg, MD; Kim A. Eagle, MD; Shaun G. Goodman, MD, MSc; Frederick A. Kim A. Eagle, MD; Shaun G. Goodman, MD, MSc; Frederick A.

Anderson, Jr, PhD; Christopher B. Granger, MD; Marcus D. Anderson, Jr, PhD; Christopher B. Granger, MD; Marcus D. Flather, MBBS, FRCP; Andrzej Budaj, MD, PhD; Ann Quill, Flather, MBBS, FRCP; Andrzej Budaj, MD, PhD; Ann Quill,

MA; Joel M. Gore, MD for the GRACE InvestigatorsMA; Joel M. Gore, MD for the GRACE Investigators

Published in JAMA Published in JAMA

May 2, 2007May 2, 2007

Global Registry of Acute Coronary Events: GRACE

Global Registry of Acute Coronary Events: GRACE


• Randomized trials provide robust evidence for the Randomized trials provide robust evidence for the impact of pharmacological and interventional impact of pharmacological and interventional treatments in patients with ST-segment elevation treatments in patients with ST-segment elevation and non-ST-segment elevation acute coronary and non-ST-segment elevation acute coronary syndromes (NSTE ACS), resulting in changes in syndromes (NSTE ACS), resulting in changes in practice guidelines.practice guidelines.

• The extent and time course of changes in clinical The extent and time course of changes in clinical practice are uncertain, however, and it is unknown practice are uncertain, however, and it is unknown whether such changes are associated with better whether such changes are associated with better outcomes. outcomes.

• Randomized trials provide robust evidence for the Randomized trials provide robust evidence for the impact of pharmacological and interventional impact of pharmacological and interventional treatments in patients with ST-segment elevation treatments in patients with ST-segment elevation and non-ST-segment elevation acute coronary and non-ST-segment elevation acute coronary syndromes (NSTE ACS), resulting in changes in syndromes (NSTE ACS), resulting in changes in practice guidelines.practice guidelines.

• The extent and time course of changes in clinical The extent and time course of changes in clinical practice are uncertain, however, and it is unknown practice are uncertain, however, and it is unknown whether such changes are associated with better whether such changes are associated with better outcomes. outcomes.

GRACE: BackgroundGRACE: Background

Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.Fox et al. JAMA. 2007 May 2; 297 (17): 1892 – 1900.


• Previous studies have documented discrepancies between Previous studies have documented discrepancies between guideline recommendations and clinical practice; thus, guideline recommendations and clinical practice; thus, there is a clinical priority to determine the extent to which there is a clinical priority to determine the extent to which evidence is applied in practice, whether this is changing evidence is applied in practice, whether this is changing over time, and whether such changes are associated with over time, and whether such changes are associated with improved outcomes. improved outcomes.

• The aim of this study was to determine whether changes in The aim of this study was to determine whether changes in hospital management of patients with ST-segment hospital management of patients with ST-segment elevation of myocardial infarction (STEMI) and NSTE ACS elevation of myocardial infarction (STEMI) and NSTE ACS are associated with improvements in clinical outcome. are associated with improvements in clinical outcome.

• Previous studies have documented discrepancies between Previous studies have documented discrepancies between guideline recommendations and clinical practice; thus, guideline recommendations and clinical practice; thus, there is a clinical priority to determine the extent to which there is a clinical priority to determine the extent to which evidence is applied in practice, whether this is changing evidence is applied in practice, whether this is changing over time, and whether such changes are associated with over time, and whether such changes are associated with improved outcomes. improved outcomes.

• The aim of this study was to determine whether changes in The aim of this study was to determine whether changes in hospital management of patients with ST-segment hospital management of patients with ST-segment elevation of myocardial infarction (STEMI) and NSTE ACS elevation of myocardial infarction (STEMI) and NSTE ACS are associated with improvements in clinical outcome. are associated with improvements in clinical outcome.

GRACE: Background (cont.)GRACE: Background (cont.)



Primary Endpoint: In-hospital death, recurrent myocardial infarction, Primary Endpoint: In-hospital death, recurrent myocardial infarction, heart failure, stroke, and cardiogenic shockheart failure, stroke, and cardiogenic shock

Primary Endpoint: In-hospital death, recurrent myocardial infarction, Primary Endpoint: In-hospital death, recurrent myocardial infarction, heart failure, stroke, and cardiogenic shockheart failure, stroke, and cardiogenic shock

NSTE ACSn=27,558NSTE ACSn=27,558

STEMIn=16,814

STEMIn=16,814

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

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

Follow-up for approximately 6 mos. after hospital dischargeFollow-up for approximately 6 mos. after hospital discharge

GRACE: Study DesignGRACE: Study Design



GRACE: Baseline CharacteristicsGRACE: Baseline Characteristics

• Patients with STEMI were more often male (72% Patients with STEMI were more often male (72% vs 65%) and were slightly younger than those with vs 65%) and were slightly younger than those with NSTE ACS (65 vs 68 years) .NSTE ACS (65 vs 68 years) .

• Patients with NSTE ACS had a more complex Patients with NSTE ACS had a more complex medical history than patients with STEMI.medical history than patients with STEMI.

• Patients with NSTE ACS were less likely to be Patients with NSTE ACS were less likely to be current smokers (21% vs 36%) and more likely to current smokers (21% vs 36%) and more likely to be past smokers (32% vs 23%). be past smokers (32% vs 23%).



Jul to Dec 1999 Jul to Dec 1999 Jul to Dec Jul to Dec 20052005

% Difference in % Difference in Rates (95% CI)Rates (95% CI)

P for P for TrendTrend

AspirinAspirin 1064/1118 (95.1)1064/1118 (95.1) 815/842 (96.7)815/842 (96.7) 1.6 (-0.1 to 3.4)1.6 (-0.1 to 3.4) < .01< .01

Beta-blockersBeta-blockers 718/858 (83.6)718/858 (83.6) 603/639 (94.3)603/639 (94.3) 11 (7.6 to 14)11 (7.6 to 14) < .001< .001

StatinsStatins 486/1302 (37.3)486/1302 (37.3) 816/955 (85.4)816/955 (85.4) 48 (45 to 52)48 (45 to 52) < .001< .001

ACE ACE inhibitor/ARBinhibitor/ARB 760/1181 (64.3)760/1181 (64.3) 714/832 (85.8)714/832 (85.8) 22 (18 to 25)22 (18 to 25) < .001< .001

FibrinolyticFibrinolytic 387/781 (49.5)387/781 (49.5) 144/517 (27.8)144/517 (27.8) -22 (-27 to -17)-22 (-27 to -17) < .001< .001

Primary PCI Primary PCI 177/1099 (16.1)177/1099 (16.1) 406/769 (52.7)406/769 (52.7) 37 (33 to 41)37 (33 to 41) < .001< .001

PCIPCI 396/1219 (32.4)396/1219 (32.4) 591/927 (63.5)591/927 (63.5) 31 (27 to 35)31 (27 to 35) < .001< .001

No reperfusionNo reperfusion 365/1069 (34.1)365/1069 (34.1) 216/754 (28.6)216/754 (28.6) -5.5 (-9.8 to -1.2)-5.5 (-9.8 to -1.2) .90.90

GRACE: Changes in Therapy for STEMI patientsGRACE: Changes in Therapy for STEMI patients



• Use of pharmacological medication increased over the study Use of pharmacological medication increased over the study period.period.

• Use of pharmacological reperfusions Use of pharmacological reperfusions ↓↓ by 22 percentage by 22 percentage points, whereas the rate of primary PCI points, whereas the rate of primary PCI ↑↑ by 37 percentage by 37 percentage points over the same interval. points over the same interval.

• Proportion of patients with STEMI who did not receive Proportion of patients with STEMI who did not receive pharmacological reperfusion therapy or primary rescue or pharmacological reperfusion therapy or primary rescue or facilitated PCI declined by 5.5 percentage points.facilitated PCI declined by 5.5 percentage points.

GRACE: Changes in Therapy for STEMI patients (cont.)GRACE: Changes in Therapy for STEMI patients (cont.)



Jul to Dec 1999 Jul to Dec 1999 Jul to Dec 2005Jul to Dec 2005 % Difference in % Difference in Rates (95% CI)Rates (95% CI)

P for P for TrendTrend

AspirinAspirin 1897/2032 (93.3)1897/2032 (93.3) 1372/1430 (95.9)1372/1430 (95.9) 2.6 (1.1 to 4.1)2.6 (1.1 to 4.1) .02.02

Beta-blockersBeta-blockers 1496/1868 (80.0)1496/1868 (80.0) 1152/1280 (90.0)1152/1280 (90.0) 9.9 (7.5 to 12)9.9 (7.5 to 12) < .001< .001

StatinsStatins 983/2442 (40.2)983/2442 (40.2) 1420/1721 (82.5)1420/1721 (82.5) 42 (40 to 45)42 (40 to 45) < .001< .001

ACE ACE inhibitor/ARBinhibitor/ARB 1210/2300 (52.6)1210/2300 (52.6) 1100/1463 (75.1)1100/1463 (75.1) 23 (20 to 26)23 (20 to 26) < .001< .001

CABGCABG 161/2360 (6.8)161/2360 (6.8) 85/1668 (5.1)85/1668 (5.1) -1.7 (-3.2 to –0.3)-1.7 (-3.2 to –0.3) .04.04

Cardiac Cardiac Catherterization Catherterization 984/2379 (41.3)984/2379 (41.3) 1045/1667 (62.6)1045/1667 (62.6) 21 (18 to 24)21 (18 to 24) < .001< .001

PCIPCI 403/2375 (16.9)403/2375 (16.9) 581/1676 (34.6)581/1676 (34.6) 18 (15 to 20)18 (15 to 20) < .001< .001

GRACE: Changes in Therapy for NSTE ACS patientsGRACE: Changes in Therapy for NSTE ACS patients



• Use of pharmacological medication increased over Use of pharmacological medication increased over the study period.the study period.

• There was a modest decrease in the use of There was a modest decrease in the use of coronary artery bypass graft (CABG) surgery of 1.7 coronary artery bypass graft (CABG) surgery of 1.7 percentage points.percentage points.

• The frequency of angiography increased markedly The frequency of angiography increased markedly by 21 percentage points, while the use of PCI by 21 percentage points, while the use of PCI increased substantially by 18 percentage points. increased substantially by 18 percentage points.

GRACE: Changes in Therapy for NSTE ACS patients (cont.)

GRACE: Changes in Therapy for NSTE ACS patients (cont.)



• Hospital deaths Hospital deaths decreased by 3.9% decreased by 3.9% (95% CI, -5.3 to -1.9) (95% CI, -5.3 to -1.9) and the rate of in-and the rate of in-hospital congestive hospital congestive heart failure (CHF) heart failure (CHF) or pulmonary edema or pulmonary edema declined by 9.0% declined by 9.0% (95% CI, -12 to -6).(95% CI, -12 to -6).8.4%

19.5%

4.6%

11.0%

0%

5%

10%

15%

20%

Death Heart Failure

Jul -Dec 1999 Jul-Dec 2005

8.4%

19.5%

4.6%

11.0%

0%

5%

10%

15%

20%

Death Heart Failure


Changes in Clinical Outcomes for Changes in Clinical Outcomes for STEMI PatientsSTEMI Patients

n = 1335n = 1335

p < .001p < .001

p < .001p < .001

Dea

th o

r C

HF

(%

)

n = 992n = 992 n = 1351n = 1351 n = 993n = 993

GRACE: Outcome Measures over TimeGRACE: Outcome Measures over Time


• Risk-adjusted hospital Risk-adjusted hospital deaths declined by 0.7 deaths declined by 0.7 percentage points percentage points (95% CI, -1.7 to 0.3 in (95% CI, -1.7 to 0.3 in NSTE ACS patients. NSTE ACS patients.

• The rate of congestive The rate of congestive heart failure and heart failure and pulmonary edema pulmonary edema decreased by 6.5% decreased by 6.5% (95% CI, -8.4 to -4.7). (95% CI, -8.4 to -4.7).

2.9%

13.0%

2.2%

6.1%

0%

5%

10%

15%

Death Heart Failure


2.9%

13.0%

2.2%

6.1%

0%

5%

10%

15%

Death Heart Failure


Changes in Clinical Outcomes for Changes in Clinical Outcomes for NSTE ACS PatientsNSTE ACS Patients

n = 2213n = 2213

p = .02p = .02

p <.001p <.001

Dea

th o

r C

HF

(%

)

n =1566 n =1566 n = 2228n = 2228 n = 1564 n = 1564

GRACE: Outcome Measures over TimeGRACE: Outcome Measures over Time


• The rate of death The rate of death between hospital between hospital discharge and 6-discharge and 6-month follow-up month follow-up decreased by 1.6% decreased by 1.6% (95% CI, -3.0 to -(95% CI, -3.0 to -0.1) in NSTE ACS 0.1) in NSTE ACS patients. patients.

4.9% 4.9%4.5%

3.3%

0%

1%

2%

3%

4%

5%

6%

STEMI NSTE ACS


4.9% 4.9%4.5%

3.3%

0%

1%

2%

3%

4%

5%

6%

STEMI NSTE ACS


Death Outcomes for STEMI and NSTE ACS Death Outcomes for STEMI and NSTE ACS patients at 6-month follow-up patients at 6-month follow-up

n = 1099n = 1099

p = .64p = .64

p = .04p = .04

Dea

th o

r C

HF

(%

)

n =620n =620 n = 1942n = 1942 n = 998 n = 998

GRACE: 6-month OutcomesGRACE: 6-month Outcomes


GRACE: LimitationsGRACE: Limitations

• The participating clusters reflect regional practices and The participating clusters reflect regional practices and outcomes but do not necessarily reflect practice for outcomes but do not necessarily reflect practice for specific countries.specific countries.

• Participating hospitals are sent feedback on a 6-month Participating hospitals are sent feedback on a 6-month basis, so it cannot be determined whether improvements basis, so it cannot be determined whether improvements in adherence to evidence-based medication are taking in adherence to evidence-based medication are taking place nationwide or are limited to participating sites.place nationwide or are limited to participating sites.

• The participating clusters reflect regional practices and The participating clusters reflect regional practices and outcomes but do not necessarily reflect practice for outcomes but do not necessarily reflect practice for specific countries.specific countries.

• Participating hospitals are sent feedback on a 6-month Participating hospitals are sent feedback on a 6-month basis, so it cannot be determined whether improvements basis, so it cannot be determined whether improvements in adherence to evidence-based medication are taking in adherence to evidence-based medication are taking place nationwide or are limited to participating sites.place nationwide or are limited to participating sites.



GRACE: Limitations (cont.)GRACE: Limitations (cont.)

• Increasing use of troponin measurement throughout the Increasing use of troponin measurement throughout the study may have led to underestimation of the detection of study may have led to underestimation of the detection of small reinfarctions if troponin was already elevated at small reinfarctions if troponin was already elevated at presentation and if the patient did not evolve new presentation and if the patient did not evolve new electrocardiographic changes of MI. electrocardiographic changes of MI.

• Increasing use of troponin measurement throughout the Increasing use of troponin measurement throughout the study may have led to underestimation of the detection of study may have led to underestimation of the detection of small reinfarctions if troponin was already elevated at small reinfarctions if troponin was already elevated at presentation and if the patient did not evolve new presentation and if the patient did not evolve new electrocardiographic changes of MI. electrocardiographic changes of MI.



GRACE: SummaryGRACE: Summary

• In this multinational observational study, improvements In this multinational observational study, improvements in the management of patients with ACS were in the management of patients with ACS were associated with significant reductions in the rates of new associated with significant reductions in the rates of new heart failure and mortality and in rates of stroke and MI heart failure and mortality and in rates of stroke and MI at 6 months. at 6 months.

• This study population is the first demonstration of This study population is the first demonstration of significant reductions observed in hospital rates of new significant reductions observed in hospital rates of new heart failure in ACS patients, over time, and of heart failure in ACS patients, over time, and of reductions in mortality. reductions in mortality.

• In this multinational observational study, improvements In this multinational observational study, improvements in the management of patients with ACS were in the management of patients with ACS were associated with significant reductions in the rates of new associated with significant reductions in the rates of new heart failure and mortality and in rates of stroke and MI heart failure and mortality and in rates of stroke and MI at 6 months. at 6 months.

• This study population is the first demonstration of This study population is the first demonstration of significant reductions observed in hospital rates of new significant reductions observed in hospital rates of new heart failure in ACS patients, over time, and of heart failure in ACS patients, over time, and of reductions in mortality. reductions in mortality.


Documents

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