Erin A Bohula1, Marc P Bonaca2, Eugene Braunwald2, Philip E Aylward2, Ramon Corbalan2, Gaetano M De Ferrari2, Ping He2, Basil S Lewis2, Piera A Merlini2, Sabina A Murphy2, Marc S Sabatine2, Benjamin M Scirica2, David A Morrow2. 1. From the TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., M.P.B., E.B., P.H., S.A.M., M.S.S., B.M.S., D.A.M.); South Australian Health and Research Institute, Flinders University and Medical Centre, Adelaide (P.E.A.); Division of Cardiovascular Diseases, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago (R.C.); Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (G.M.D.F.); Lady Davis Carmel Medical Center and the Ruth and Bruce Rappaport School of Medicine, Technion, Haifa, Israel (B.S.L.); and IV Divisione Cardiologia, Azienda Ospedaliera Niguarda Ca' Granda, Milan, Italy (P.A.M.). ebohula@partners.org. 2. From the TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., M.P.B., E.B., P.H., S.A.M., M.S.S., B.M.S., D.A.M.); South Australian Health and Research Institute, Flinders University and Medical Centre, Adelaide (P.E.A.); Division of Cardiovascular Diseases, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago (R.C.); Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (G.M.D.F.); Lady Davis Carmel Medical Center and the Ruth and Bruce Rappaport School of Medicine, Technion, Haifa, Israel (B.S.L.); and IV Divisione Cardiologia, Azienda Ospedaliera Niguarda Ca' Granda, Milan, Italy (P.A.M.).
Abstract
BACKGROUND:Patients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar. METHODS: We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2.5 years (median) inTRA 2°P-TIMI 50 [Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50]. The efficacy and safety of vorapaxar (SCH 530348; MK-5348) were assessed by baseline risk among patients with previous MI without prior stroke or transient ischemic attack for whom there is a clinical indication for vorapaxar. End points were cardiovascular death, MI, or ischemic stroke and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding. RESULTS: The 9 independent risk predictors were age, diabetes mellitus, hypertension, smoking, peripheral arterial disease, previous stroke, previous coronary bypass grafting, heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of cardiovascular death/MI/ischemic stroke and the individual components (P for trend <0.001 for all). High-risk patients (≥3 risk indicators; 20% of population) had a 3.2% absolute risk reduction in cardiovascular disease/MI/ischemic stroke with vorapaxar, and intermediate-risk patients (1-2 risk indicators; 61%) had a 2.1% absolute risk reduction (P<0.001 each), translating to a number needed to treat of 31 and 48. Bleeding increased across risk groups (P for trend<0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients. CONCLUSIONS: Stratification of baseline atherothrombotic risk can assist with therapeutic decision making for vorapaxar use for secondary prevention after MI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00526474.
RCT Entities:
BACKGROUND:Patients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar. METHODS: We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2.5 years (median) in TRA 2°P-TIMI 50 [Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50]. The efficacy and safety of vorapaxar (SCH 530348; MK-5348) were assessed by baseline risk among patients with previous MI without prior stroke or transient ischemic attack for whom there is a clinical indication for vorapaxar. End points were cardiovascular death, MI, or ischemic stroke and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding. RESULTS: The 9 independent risk predictors were age, diabetes mellitus, hypertension, smoking, peripheral arterial disease, previous stroke, previous coronary bypass grafting, heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of cardiovascular death/MI/ischemic stroke and the individual components (P for trend <0.001 for all). High-risk patients (≥3 risk indicators; 20% of population) had a 3.2% absolute risk reduction in cardiovascular disease/MI/ischemic stroke with vorapaxar, and intermediate-risk patients (1-2 risk indicators; 61%) had a 2.1% absolute risk reduction (P<0.001 each), translating to a number needed to treat of 31 and 48. Bleeding increased across risk groups (P for trend<0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients. CONCLUSIONS: Stratification of baseline atherothrombotic risk can assist with therapeutic decision making for vorapaxar use for secondary prevention after MI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00526474.
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