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Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE)

BMJ 2006; 333 doi: (Published 23 November 2006) Cite this as: BMJ 2006;333:1091
  1. Keith A A Fox, British Heart Foundation professor of cardiology1,
  2. Omar H Dabbous, statistician2,
  3. Robert J Goldberg, epidemiologist2,
  4. Karen S Pieper, statistician3,
  5. Kim A Eagle, cardiologist4,
  6. Frans Van de Werf, cardiologist5,
  7. Álvaro Avezum, cardiologist6,
  8. Shaun G Goodman, cardiologist7,
  9. Marcus D Flather, cardiologist8,
  10. Frederick A Anderson Jr, research professor of surgery2,
  11. Christopher B Granger, cardiologist3
  1. 1Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh EH16 4SB
  2. 2University of Massachusetts Medical School, Worcester, MA 01655, USA
  3. 3Duke Clinical Research Institute, Durham, NC 27705, USA
  4. 4University of Michigan Cardiovascular Center, Ann Arbor, MI 48109-0477, USA
  5. 5Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium 3000
  6. 6Dante Pazzanese Institute of Cardiology, 04012-909 Sao Paulo, Brazil
  7. 7Terrence Donnelly Heart Centre, Division of Cardiology, St Michael's Hospital, Toronto, ON, Canada M5B 1W8
  8. 8Royal Brompton and Harefield NHS Trust, Royal Brompton Hospital, London SW3 6NP
  1. Correspondence to: K A A Fox{at}
  • Accepted 12 September 2006


Objective To develop a clinical risk prediction tool for estimating the cumulative six month risk of death and death or myocardial infarction to facilitate triage and management of patients with acute coronary syndrome.

Design Prospective multinational observational study in which we used multivariable regression to develop a final predictive model, with prospective and external validation.

Setting Ninety four hospitals in 14 countries in Europe, North and South America, Australia, and New Zealand.

Population 43 810 patients (21 688 in derivation set; 22 122 in validation set) presenting with acute coronary syndrome with or without ST segment elevation enrolled in the global registry of acute coronary events (GRACE) study between April 1999 and September 2005.

Main outcome measures Death and myocardial infarction.

Results 1989 patients died in hospital, 1466 died between discharge and six month follow-up, and 2793 sustained a new non-fatal myocardial infarction. Nine factors independently predicted death and the combined end point of death or myocardial infarction in the period from admission to six months after discharge: age, development (or history) of heart failure, peripheral vascular disease, systolic blood pressure, Killip class, initial serum creatinine concentration, elevated initial cardiac markers, cardiac arrest on admission, and ST segment deviation. The simplified model was robust, with prospectively validated C-statistics of 0.81 for predicting death and 0.73 for death or myocardial infarction from admission to six months after discharge. The external applicability of the model was validated in the dataset from GUSTO IIb (global use of strategies to open occluded coronary arteries).

Conclusions This risk prediction tool uses readily identifiable variables to provide robust prediction of the cumulative six month risk of death or myocardial infarction. It is a rapid and widely applicable method for assessing cardiovascular risk to complement clinical assessment and can guide patient triage and management across the spectrum of patients with acute coronary syndrome.


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  • We thank the physicians and nurses who participated in GRACE. The risk calculator is available together with further information about the project and the complete list of participants from We thank Sophie Rushton-Smith for editorial services.

  • Contributors: KAAF, RJG, KAE, FVdeW, ÁA, SGG, FAA, and CBG were responsible for study concept and design. KAAF, KAE, FVdeW, ÁA, SGG, and CBG acquired the data. KAAF drafted the manuscript and is guarantor. All authors critically revised the manuscript for important intellectual content and approved the final version. OHD and KSP carried out statistical analyses.

  • Funding: The GRACE Registry is supported by an unrestricted educational grant from Sanofi-Aventis to the Center for Outcomes Research, University of Massachusetts Medical School. Sophie Rushton-Smith was funded by Sanofi-Aventis.

  • Competing interests: KAAF has received grant funding from the British Heart Foundation and his department is supported by the British Heart Foundation, Medical Research Council, Wellcome Trust, Sanofi-Aventis, Bristol-Myers Squibb, and MSD. KAE has received grants from Biosite, Bristol-Myers Squibb, Cardiac Sciences, Blue Cross Blue Shield of Michigan, Hewlett Foundation, Mardigian Fund, Sanofi-Aventis, Varbedian Fund, National Heart, Lung and Blood NIH, and Pfizer. FVdeW has received research grants from Boehringer Ingelheim, Sanofi-Aventis, Proctor and Gamble, Servier, Novartis, MSD, and Schering Plough. ÁA has received funding from Sanofi-Aventis, Population Health Research Institute, and Boehringer Ingelheim. SGG has received funding from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Hoffmann-LaRoche Pharmaceuticals, Merck, Novartis, Pfizer, Sanofi-Synthelabo, Schering Corp, and Millennium Pharmaceuticals. MDF, FAA, CBG, and BK have all received funding from Sanofi-Aventis.

  • Ethical approval: Approval was obtained from local institutional review boards.

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