The Late Consequences of Acute Coronary Syndromes: 2-Year Follow-up Outcomes, Procedures, and Treatment of Patients from the Global Registry of Acute Coronary Events (GRACE) S Goodman 1, W Huang 2, JM Gore 2, PG Steg 3, KA Eagle 4, FA Anderson 2, KAA Fox 5 1 Canadian Heart Research Centre and St. Michael's Hospital, University of Toronto, Toronto, Canada 2 Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA, United States 3 Assistance Publique-Hopitaux de Paris, Hopital Bichat, Universite Paris 7 Denis Diderot, INSERM U-69, Paris, France 4 University of Michigan Medical Center, Ann Arbor, MI, United States 5 Cardiovascular Research, Division of Medical & Radiological Sciences, The University of Edinburgh, Edinburgh, United Kingdom
Funding GRACE was funded by an unrestricted grant from sanofi-aventis, Paris, France 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, and in the decision to submit, the abstract Conflict of Interest None
Background The early risks of death and myocardial (re)infarction (MI) have been well characterized following an acute coronary syndrome (ACS) However, the later evidence-based management and consequences in this patient population remain less clearly defined Further, the value of risk predictors of shortterm outcome (e.g., in-hospital and 6-month) from the GRACE Risk Scores in predicting longer-term outcome (e.g., >1 year) has been limited to-date 1,2 1 Tang et al Am Heart J 2007;153:29-35 2 Fox et al Eur Heart J 2010;31:2755-64
Purpose The large (n=70,395), prospective, multinational (123 hospitals from 14 countries) observational GRACE program (1999-2009) was established with the aim of improving the quality of care for patients with ACS by describing differences in, and relationships between, patient characteristics, treatment, and management practices, and hospital and post-discharge (6- month) outcomes The GRACE Investigators Am Heart J 2001;141:190-9 Goodman et al Am Heart J 2009;158:193-201 Fox et al Heart 2010;96:1095-1101
2-Year Follow-Up In 2004, 2-year follow-up was undertaken in patients with a discharge diagnosis of ACS in 57 sites where ethics approval, patient consent, and logistics allowed To describe the: Objectives Longer-term outcomes, procedures, and evidence-based medication use Value of the GRACE Risk Score 1 in predicting 2-year mortality 1 Eagle et al JAMA 2004;291:2727-33
Inclusion Criteria Patients 18 years old admitted with suspected ACS, with at least one of the following: ECG changes consistent with ACS Abnormal cardiac biomarker Documentation of coronary artery disease Qualifying ACS must not have been precipitated or accompanied by a significant co-morbid condition (e.g., motor vehicle accident, trauma, severe gastrointestinal bleeding, operation, or procedure) The GRACE Investigators Am Heart J 2001;141:190-9
Discharge Diagnosis All cases assigned to one of the following mutually exclusive categories based on presenting ECG characteristics, cardiac biomarker status during hospitalization, and final hospital diagnosis: ST-segment elevation or new left bundle branch block (LBBB) MI (STEMI); Non-ST-segment elevation MI (NSTEMI); or Unstable angina (UA)
Patient Flow 70,395 pts enrolled in GRACE (123 hospitals, 14 countries, 1999-2007) 65,127 diagnosed with ACS 21,055 potentially eligible pts (2004-7) at participating sites (N=57) where ethics approval, patient consent, and logistics allowed 12,044 pts (57.2%) had 2 year follow-up
Selected Patient Characteristics at Admission Characteristic STEMI (n=4,199) NSTEMI (n=4,274) U. Angina (n=3651) Age, median yrs (IQR) 62 (53-73) 67 (57-77) 64 (56-74) Female (%) 31 27 34 Prior MI (%) 19 33 43 Prior PCI / CABG (%) 12 / 6 20 / 16 32 / 20 Prior Heart Failure (%) 4 12 9 Diabetes (%) 20 28 27 Hypertension (%) 56 69 74 Dyslipidemia (%) 43 57 66 Killip Class I (%) 87 86 91 GRACE Risk Score, median (IQR) 138 (117-160) 128 (104-152) 108 (90-127)
Selected In-Hospital Procedures Procedure STEMI (n=4,199) NSTEMI (n=4,274) U. Angina (n=3651) Cardiac Catheterization (%) 86 75 63 PCI (%) 68 42 34 CABG (%) 4.3 7.2 6.0
Selected In-Hospital Events Event STEMI (n=4,199) NSTEMI (n=4,274) U. Angina (n=3651) Reinfarction (%) 3.1 2.5 - Cardiogenic Shock (%) 2.9 0.8 0.4 Heart Failure (%) 13 10 4 Stroke (%) 0.5 0.4 0.3 Major Bleeding (%) 2.5 1.9 1.4
Selected Discharge Therapies 100 80 60 40 % of Patients ASA 95 90 91 87 91 89 Clopidogrel/ Ticlopidine % of Patients 74 62 54 Other Antiplatelet/ Anticoagulant % of Patients Discharge 2-Years 20 0 STEMI NSTEMI UA 16 STEMI 18 NSTEMI UA 22 7 7 STEMI 7 9 NSTEMI 6 7 UA
Selected Discharge Therapies 100 80 60 40 20 Beta Blocker % of Patients 88 83 85 81 81 77 ACE Inhibitor/Angiotensin Receptor Blocker % of Patients 80 72 72 68 Discharge 2-Years 67 64 Statin/Other Lipid Lowering Agent % of Patients 90 88 85 85 85 83 0 STEMI NSTEMI UA STEMI NSTEMI UA STEMI NSTEMI UA
Selected 2-Year Procedures Procedure STEMI (n=4,199) NSTEMI (n=4,274) U. Angina (n=3651) Cardiac Catheterization (%) 10 13 15 PCI (%) 5 7 8 CABG (%) 1.2 1.4 1.6
Selected 2-Year Events Event STEMI (n=4,199) NSTEMI (n=4,274) U. Angina (n=3651) Death (%) 4.9 7.6 4.4 Cardiovascular (CV) Death (%) 2.8 4.1 2.6 MI (%) 2.8 4.0 3.8 Stroke (%) 1.0 1.6 1.1 Heart Failure (%) 4.1 6.4 6.0 Unscheduled CV Hospitalization (%) 14.2 18.4 23.9 Any unscheduled procedure + (%) 11.1 13.7 15.4 Compared to STEMI, NSTEMI patients experienced significantly higher age- and gender-adjusted rates of: Death (OR 1.25 [1.03-1.52]) Recurrent MI (OR 1.36 [1.04-1.77]) Heart Failure (OR 1.39 [1.11-1.73]) + Cardiac Catheterization, PCI, and/or CABG Unscheduled CV rehospitalization (OR 1.34 [1.18-1.53])
2-Year Mortality Main Cause of Death STEMI (n=4,199) NSTEMI (n=4,274) U. Angina (n=3651) Total (%) 183 (4.9) 302 (7.6) 149 (4.4) Cardiac (%) 91 (50) 136 (45) 77 (52) Non-cardiac (%) 71 (39) 114 (38) 54 (36) Unknown (%) 21 (11) 52 (17) 18 (12)
Event-free Survival 1.00 2-Year Survival by GRACE Risk Score 0.988 0.95 0.90 0.85 0.80 GRACE Risk Score highly predictive of all-cause mortality at 2 years (c-statistic 0.80) Lower Risk [GRACE Score 108] (n=6,068) Intermediate Risk [109-140] (n=3,110) Higher Risk [>140](n=1,440) 0.75 0 100 200 300 400 500 600 700 Days since Hospital Discharge Log rank test p<0.001 0.950 0.829 800
Limitations Although standard definitions provided for all clinical outcomes, events (including type of death) were not systematically validated or centrally adjudicated Only 57% (12,044/21,055) of potentially eligible patients had complete 2-yr follow-up data post-discharge morbidity and mortality experience of patients may have differed Inability to identify other potential clinical, socioeconomic, or lifestyle factors associated with longer-term outcome post-acs
Conclusions GRACE Risk Score maintained good predictive value at 2 years 2-year post-discharge morbidity and mortality higher in NSTEMI vs. STEMI, even amongst a cohort where the majority continue to receive guideline-recommended medical therapies However, ~40% of deaths appear to be from non-cardiac causes poses a challenge to the management efforts to further reduce post-acs mortality
Scientific Advisory Committee Co-Chairs Joel Gore, USA Keith Fox, UK Publication Committee Co-Chairs Kim Eagle, USA Gabriel Steg, France Argentina Enrique Gurfinkel Australia /New Zealand David Brieger Austria Werner Klein Belgium Frans van de Werf Brazil Álvaro Avezum Canada Shaun Goodman Germany Dietrich Gulba Italy Giancarlo Agnelli France Gilles Montalescot Gabriel Steg Poland Andrzej Budaj Spain José López-Sendón Switzerland Felix Gutzwiller United Kingdom Keith Fox United States Frederick Anderson Christopher Cannon Kim Eagle Robert Goldberg Michael Howard Joel Gore Christopher Granger Brian Kennelly
2-Year Follow-Up Investigators Country Argentina Australia Austria Belgium Brazil Canada France Germany New Zealand Poland Spain United Kingdom United States Principal Investigators Enrique Gurfinkel, Maria Caridi, Edgardo Beck, Nadia Budassi Jon Waites, John Counsell, Craig Juergens, David Brieger, Jeffrey Lefkovits Georg Gaul, Harald Simader, Wolfgang Schellnegger Frans Van de Werf, Patrick Coussement, Charles Henuzet, Marc Renard, Manuel Quiñonez, Herbert De Raedt Roberto Marino, Antonio Carvalho, Ari Timerman, Denilson Albuquerque, Mario Coutinho, José Esteves, Lília Nigro Maia Shaun Goodman, James Cha, Maria DeVilla, Roland Leader, Rajen Chetty, Frederick Spencer Gilles Montalescot, Ph. Gabriel Steg Harm Ohlmeier Gerard Devlin, John Elliott Andrzej Budaj, Wlodzimierz Krasowski, Michat Szpajer Fernando Worner, Rafael Rubio, José López-Sendón Keith Fox, I. Starkey, Ashok Jacob Joel Gore, Kim Eagle, Christopher Granger, Brian Kennelly, Joel Rubenstein, Michael Moran, Leslie Kern, M. Alycia Hassett, James Zidar, Michael Moran, Bradley Hubbard
Selected Patient Characteristics at Admission: Included vs. Not Included Characteristic Included (n=12,044) Not Included (n=9,011) Age, median yrs (IQR) 62 (53-73) 67 (57-77) Female (%) 31 31 Prior MI (%) 31 28 Prior PCI / CABG (%) 21 / 14 20 / 11 Prior Heart Failure (%) 9 8 Diabetes (%) 25 25 Hypertension (%) 66 62 Dyslipidemia (%) 55 51 Killip Class I (%) 88 88 GRACE Risk Score, median (IQR) 126 (103-150) 126 (103-151)
Selected In-Hospital Procedures and Events: Included vs. Not Included Characteristic Included (n=12,044) Not Included (n=9,011) Cardiac Catheterization (%) 75 75 PCI (%) 48 51 CABG (%) 5.9 5.4 Reinfarction (%) 1.9 1.9 Cardiogenic Shock (%) 1.4 1.7 Heart Failure (%) 9 8 Stroke (%) 0.4 0.5 Major Bleeding (%) 2.0 2.1
Selected Discharge Therapies: Included vs. Not Included Characteristic Included (n=12,044) Not Included (n=9,011) ASA (%) 92 92 Clopidogrel/Ticlopidine (%) 64 68 Warfarin (%) 7.0 6.4 Beta-Blocker (%) 85 83 ACE Inhibitor (%) 67 70 Statin (%) 85 87