A comparison of the clinical impact of bleeding measured by two different classifications among patients with acute coronary syndromes.

OBJECTIVES The goal of this study was to determine the association between Thrombolysis In Myocardial Infarction (TIMI) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding and clinical outcomes. BACKGROUND There are limited data on the relative utility of either scale at predicting clinical outcomes in patients with non-ST-segment elevation acute coronary syndromes (ACS). METHODS Pooled data from two randomized trials of patients with ACS (n = 15,454) were analyzed to determine the association between TIMI and GUSTO bleeding and 30-day and 6-month death/myocardial infarction (MI) using Cox proportional hazards modeling that included bleeding as a time-dependent covariate. RESULTS There was a stepwise increase in the adjusted hazard of 30-day death/MI with worsening GUSTO bleeding (hazard ratio [95% confidence interval], GUSTO mild 1.20 [1.05 to 1.37]; moderate 3.28 [2.88 to 3.73]; severe 5.57 [4.33 to 7.17]), and an increased risk with all three levels of TIMI bleeding (TIMI minimal 1.84 [1.63 to 2.08]; TIMI minor 1.64 [1.31 to 2.04]; major 1.45 [1.23 to 1.70]). When both bleeding scales were included in the same model, the risk with GUSTO bleeding persisted; however, the association between TIMI bleeding and outcome was no longer significant. CONCLUSIONS Both scales identify ACS patients with bleeding complications at risk for adverse outcomes. In a model that included both definitions, the risk with GUSTO bleeding persisted while the risk with TIMI bleeding did not. This suggests that bleeding assessed with clinical criteria is more important than that assessed by laboratory criteria in terms of outcomes. Future clinical trials should consider using a combination of the GUSTO bleeding scale and the need for transfusion to assess bleeding complications.

[1]  N. Weissman,et al.  Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions. , 2003, The American journal of cardiology.

[2]  Marshall A. Lichtman,et al.  Commentary on and reprint of EPIC (Evaluation of 7E3 for the Prevention of Ischemic Complications) Investigators, The, Use of monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty, in New England Journal of Medicine (1994) 330:956–961 , 2000 .

[3]  E. Braunwald,et al.  Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. , 2001, The New England journal of medicine.

[4]  T. Investigators.  Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. The RESTORE Investigators. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis. , 1997, Circulation.

[5]  R. Califf,et al.  Heparin dosing and outcome in acute coronary syndromes: The GUSTO-IIb experience , 2002 .

[6]  G. Wells,et al.  A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. , 1999, The New England journal of medicine.

[7]  M. Cohen,et al.  Prospective comparison of hemorrhagic complications after treatment with enoxaparin versus unfractionated heparin for unstable angina pectoris or non-ST-segment elevation acute myocardial infarction. , 2001, The American journal of cardiology.

[8]  Epic Investigators,et al.  Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. , 1994, The New England journal of medicine.

[9]  P. Armstrong,et al.  Bleeding events with abciximab in acute coronary syndromes without early revascularization: An analysis of GUSTO IV-ACS. , 2004, American heart journal.

[10]  Werner Klein,et al.  Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE) , 2003 .

[11]  R Roberts,et al.  Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. , 1987, Circulation.

[12]  K. Alexander,et al.  Representation of elderly persons and women in published randomized trials of acute coronary syndromes. , 2001, JAMA.

[13]  Dwight E. Peake,et al.  Thrombolysis in myocardial infarction (TIMI) trial: Phase I. A comparison between intravenous tissue plasminogen activator and intravenous streptokinase , 1988 .

[14]  R. Califf,et al.  Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. , 2004, JAMA.

[15]  Sunil V. Rao,et al.  Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. , 2004, JAMA.

[16]  Frans Van de Werf,et al.  An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. , 1993, The New England journal of medicine.

[17]  M. Simoons.  A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. , 1996, The New England journal of medicine.

[18]  E W Steyerberg,et al.  Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. , 2000, Circulation.

[19]  L. Fisher,et al.  Time-dependent covariates in the Cox proportional-hazards regression model. , 1999, Annual review of public health.

[20]  Epilog Investigators,et al.  Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. , 1997, The New England journal of medicine.