Vorapaxar in Patients With Diabetes Mellitus and Previous Myocardial Infarction: Findings From the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 Trial
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Background—: Vorapaxar reduces cardiovascular death, myocardial infarction (MI), or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus (DM) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis. Methods and Results—: We examined the efficacy of vorapaxar in patients with and without DM who qualified for the trial with a previous MI. Because vorapaxar is contraindicated in patients with a history of stroke or transient ischemic attack, the analysis (n=16 896) excluded such patients. The primary end point of cardiovascular death, MI, or stroke occurred more frequently in patients with DM than in patients without DM (rates in placebo group: 14.3% versus 7.6%; adjusted hazard ratio, 1.47; P <0.001). In patients with DM (n=3623), vorapaxar significantly reduced the primary end point (11.4% versus 14.3%; hazard ratio, 0.73 [95% confidence interval, 0.60–0.89]; P =0.002) with a number needed to treat to avoid 1 major cardiovascular event of 29. The incidence of moderate/severe bleeding was increased with vorapaxar in patients with DM (4.4% versus 2.6%; hazard ratio, 1.60 [95% confidence interval, 1.07–2.40]). However, net clinical outcome integrating these 2 end points (efficacy and safety) was improved with vorapaxar (hazard ratio, 0.79 [95% confidence interval, 0.67–0.93]). Conclusions—: In patients with previous MI and DM, the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of recurrent ischemic events. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00526474.
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Because rivaroxaban's ischemic benefit was consistent in the diabetes subgroup, low-dose anticoagulation added to antiplatelet therapy may be another secondary prevention option in type 2 diabetes with stable coronary disease.
“The ischemic benefits of rivaroxaban were consistent in the subgroup with diabetes mellitus, suggesting that low-dose anticoagulation added to antiplatelet therapy may be another option for secondary prevention in patients with T2DM and stable CAD.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [56]
In COMPASS, rivaroxaban increased bleeding, though fatal bleeding was not significantly increased.
“There was an associated increased risk of bleeding with rivaroxaban, although no significant excess in fatal bleeding was noted.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [56]
In COMPASS, major adverse cardiovascular events were significantly less frequent with rivaroxaban plus aspirin than with aspirin alone or rivaroxaban alone.
“The risk of major adverse cardiovascular events (MACEs) was significantly lower with the combination of rivaroxaban plus aspirin compared with either aspirin alone or rivaroxaban alone.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [56]
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- Authors
- Cavender, M. A., Scirica, B. M., Bonaca, M. P., Angiolillo, D. J., Dalby, A. J., Dellborg, M., Morais, J., Murphy, S. A., Ophuis, T. O., Tendera, M., Braunwald, E., & Morrow, D. A.
- Affiliations
- Brigham and Women's Hospital (US)
- From TIMI Study Group, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (M.A.C., B.M.S., M.P.B., S.A.M., E.B., D.A.M.); University of Florida College of Medicine, Jacksonville (D.J.A.); Milpark Hospital, Johannesburg, South Africa (A.J.D.); Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (M.D.); Santo Andre’s Hospital, Leiria, Portugal (J.M.); Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The...
- Corresponding author
- Morrow, David A.
- ORCID
- Venue
- Circulation
- Published
- 2015-03-24
- Volume
- 131
- Issue
- 12
- Pages
- 1047-1053
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC4365950
- OpenAlex
- W2086976004
- Cited by
- 80
- References
- 21
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 3 · 2020: 5 · 2019: 7 · 2018: 10 · 2017: 14 · 2016: 12 · 2015: 14
- FWCI
- 12.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Circulation (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- 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, diabetes mellitus, myocardial infarction, thrombin receptor antagonist, secondary prevention, major adverse cardiovascular events, bleeding risk, recurrent ischemic events, net clinical benefit
- MeSH terms
- Aged, Death, Diabetes Mellitus, Double-Blind Method, Female, Humans, Lactones, Male, Middle Aged, Myocardial Infarction, Pyridines, Thrombosis, Treatment Outcome, Receptors, Thrombin, Stroke, Secondary Prevention
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