Atherothrombotic Risk Stratification and the Efficacy and Safety of Vorapaxar in Patients With Stable Ischemic Heart Disease and Previous Myocardial Infarction
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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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Risk scores and other cardiovascular biomarkers have been developed for risk stratification of secondary prevention patients but are not yet in widespread use.
“Recently, risk scores and other cardiovascular biomarkers have been developed for risk strati fi cation of secondary prevention patients (i.e., those who are already high risk because they have ASCVD) but are not yet in widespread use (17,18).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [18]
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- Authors
- Bohula, E. A., Bonaca, M. P., Braunwald, E., Aylward, P. E., Corbalan, R., De Ferrari, G. M., He, P., Lewis, B. S., Merlini, P. A., Murphy, S. A., Sabatine, M. S., Scirica, B. M., & Morrow, D. A.
- Affiliations
- Brigham and Women's Hospital (US)
- 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,...
- ORCID
- Venue
- Circulation
- Published
- 2016-07-26
- Volume
- 134
- Issue
- 4
- Pages
- 304-313
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2498004564
- Cited by
- 168
- References
- 18
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 11 · 2023: 15 · 2022: 15 · 2021: 26 · 2020: 18 · 2019: 28 · 2018: 21 · 2017: 18 · 2016: 1
- FWCI
- 18.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- vorapaxar, thrombin receptor antagonist, stable coronary artery disease, myocardial infarction, secondary prevention, risk predictors, cardiovascular mortality, ischemic stroke, hemorrhage, number needed to treat, intracranial hemorrhage
- MeSH terms
- Aged, Double-Blind Method, Female, Hemorrhage, Humans, Lactones, Male, Middle Aged, Myocardial Infarction, Platelet Aggregation Inhibitors, Pyridines, Recurrence, Proportional Hazards Models, Treatment Outcome, Myocardial Ischemia, Risk Assessment, Atherosclerosis, Kaplan-Meier Estimate, Secondary Prevention
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