The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making.

CONTEXT Patients with unstable angina/non-ST-segment elevation myocardial infarction (MI) (UA/NSTEMI) present with a wide spectrum of risk for death and cardiac ischemic events. OBJECTIVE To develop a simple risk score that has broad applicability, is easily calculated at patient presentation, does not require a computer, and identifies patients with different responses to treatments for UA/NSTEMI. DESIGN, SETTING, AND PATIENTS Two phase 3, international, randomized, double-blind trials (the Thrombolysis in Myocardial Infarction [TIMI] 11B trial [August 1996-March 1998] and the Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI trial [ESSENCE; October 1994-May 1996]). A total of 1957 patients with UA/NSTEMI were assigned to receive unfractionated heparin (test cohort) and 1953 to receive enoxaparin in TIMI 11B; 1564 and 1607 were assigned respectively in ESSENCE. The 3 validation cohorts were the unfractionated heparin group from ESSENCE and both enoxaparin groups. MAIN OUTCOME MEASURES The TIMI risk score was derived in the test cohort by selection of independent prognostic variables using multivariate logistic regression, assignment of value of 1 when a factor was present and 0 when it was absent, and summing the number of factors present to categorize patients into risk strata. Relative differences in response to therapeutic interventions were determined by comparing the slopes of the rates of events with increasing score in treatment groups and by testing for an interaction between risk score and treatment. Outcomes were TIMI risk score for developing at least 1 component of the primary end point (all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization) through 14 days after randomization. RESULTS The 7 TIMI risk score predictor variables were age 65 years or older, at least 3 risk factors for coronary artery disease, prior coronary stenosis of 50% or more, ST-segment deviation on electrocardiogram at presentation, at least 2 anginal events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum cardiac markers. Event rates increased significantly as the TIMI risk score increased in the test cohort in TIMI 11B: 4.7% for a score of 0/1; 8.3% for 2; 13. 2% for 3; 19.9% for 4; 26.2% for 5; and 40.9% for 6/7 (P<.001 by chi(2) for trend). The pattern of increasing event rates with increasing TIMI risk score was confirmed in all 3 validation groups (P<.001). The slope of the increase in event rates with increasing numbers of risk factors was significantly lower in the enoxaparin groups in both TIMI 11B (P =.01) and ESSENCE (P =.03) and there was a significant interaction between TIMI risk score and treatment (P =. 02). CONCLUSIONS In patients with UA/NSTEMI, the TIMI risk score is a simple prognostication scheme that categorizes a patient's risk of death and ischemic events and provides a basis for therapeutic decision making. JAMA. 2000;284:835-842

[1]  J Col,et al.  Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international trial of 41,021 patients. GUSTO-I Investigators. , 1995, Circulation.

[2]  R. Califf,et al.  Acute Coronary Syndromes in the GUSTO-IIb Trial Prognostic Insights and Impact of Recurrent Ischemia , 1998 .

[3]  R B D'Agostino,et al.  Do patients' coronary risk factor reports predict acute cardiac ischemia in the emergency department? A multicenter study. , 1992, Journal of clinical epidemiology.

[4]  L. Wallentin,et al.  Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. The FRISC study group. , 1996, Circulation.

[5]  A. Jaffe,et al.  31st Bethesda Conference. Emergency Cardiac Care. Task force 2: Acute coronary syndromes: Section 2B--Chest discomfort evaluation in the hospital. , 2000, Journal of the American College of Cardiology.

[6]  V. Fuster,et al.  The broad spectrum of unstable angina pectoris and its implications for future controlled trials. , 1986, The American journal of cardiology.

[7]  E. Antman,et al.  Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction. TIMI 11B-ESSENCE meta-analysis. , 1999, Circulation.

[8]  R. Collins,et al.  Selection of reperfusion therapy for individual patients with evolving myocardial infarction. , 1997, European heart journal.

[9]  E. Braunwald Unstable angina : diagnosis and management , 1994 .

[10]  S. Willich,et al.  High-risk subgroups of patients with non-Q wave myocardial infarction based on direction and severity of ST segment deviation. , 1987, American heart journal.

[11]  C H Schmid,et al.  An empirical study of the effect of the control rate as a predictor of treatment efficacy in meta-analysis of clinical trials. , 1998, Statistics in medicine.

[12]  D Wybenga,et al.  Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. , 1996, The New England journal of medicine.

[13]  L. Klein,et al.  Unstable angina and non-Q wave myocardial infarction: does the clinical diagnosis have therapeutic implications? , 1999, Journal of the American College of Cardiology.

[14]  C. Heeschen,et al.  Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators. , 1999, The New England journal of medicine.

[15]  R. Califf,et al.  A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. , 1997 .

[16]  C. Cannon,et al.  The electrocardiogram predicts one-year outcome of patients with unstable angina and non-Q wave myocardial infarction: results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial Ischemia. , 1997, Journal of the American College of Cardiology.

[17]  E. Steyerberg,et al.  Nerve function in leprosy , 2000, The Lancet.

[18]  J P Ornato,et al.  Use of the Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI) To Assist with Triage of Patients with Chest Pain or Other Symptoms Suggestive of Acute Cardiac Ischemia: A Multicenter, Controlled Clinical Trial , 1998, Annals of Internal Medicine.

[19]  E. Antman,et al.  Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial. , 1999, Circulation.

[20]  D. Hosmer,et al.  Applied Logistic Regression , 1991 .

[21]  Ric,et al.  CARDIAC TROPONIN T LEVELS FOR RISK STRATIFICATION IN ACUTE MYOCARDIAL ISCHEMIA , 2000 .

[22]  Utsch,et al.  ABCIXIMAB IN PATIENTS WITH REFRACTORY UNSTABLE ANGINA IN RELATION TO SERUM TROPONIN T LEVELS BENEFIT OF ABCIXIMAB IN PATIENTS WITH REFRACTORY UNSTABLE ANGINA IN RELATION TO SERUM TROPONIN T LEVELS , 2000 .

[23]  Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. , 1998, The New England journal of medicine.

[24]  oldmann,et al.  EMERGENCY ROOM TRIAGE OF PATIENTS WITH ACUTE CHEST PAIN BY MEANS OF RAPID TESTING FOR CARDIAC TROPONIN T OR TROPONIN I , 2000 .

[25]  L. Klein,et al.  Risk stratification in unstable angina. Prospective validation of the Braunwald classification. , 1995, JAMA.

[26]  J. Hanley,et al.  The meaning and use of the area under a receiver operating characteristic (ROC) curve. , 1982, Radiology.

[27]  E F Cook,et al.  Acute chest pain in the emergency room. Identification and examination of low-risk patients. , 1985, Archives of internal medicine.

[28]  K. Thygesen,et al.  Applicability of cardiac troponin T and I for early risk stratification in unstable coronary artery disease. TRIM Study Group. Thrombin Inhibition in Myocardial ischemia. , 1997, Circulation.

[29]  F Van de Werf,et al.  Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb Investigators. , 1999, The New England journal of medicine.

[30]  V. Fuster,et al.  Usefulness of ST-segment changes in ≥2 leads on the emergency room electrocardiogram in either unstable angina pectoris or non-Q-wave myocardial infarction in predicting outcome , 1991 .

[31]  R. Centor,et al.  Throat cultures and rapid tests for diagnosis of group A streptococcal pharyngitis. , 1986, Annals of internal medicine.

[32]  L. Wallentin,et al.  Very early risk stratification by electrocardiogram at rest in men with suspected unstable coronary heart disease , 1993, Journal of internal medicine.

[33]  A. Rebuzzi,et al.  Need for a composite risk stratification of patients with unstable coronary syndromes tailored to clinical practice. , 1997, Circulation.