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Associations between use of prasugrel vs clopidogrel and outcomes by type of acute coronary syndrome: an analysis from the PROMETHEUS registry

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Abstract

We sought to investigate the utilization of prasugrel and its association with outcomes relative to clopidogrel in three typical subgroups of ACS in a real-world setting. Prasugrel is superior to clopidogrel for reducing risk of ischemic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), but is associated with an increased risk of bleeding complications. PROMETHEUS was a retrospective multicenter observational study of 19,913 ACS patients undergoing PCI from 8 centers in the United States between 2010 and 2013. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause mortality, myocardial infarction, stroke or unplanned revascularization. The study cohort included 3285 (16.5%) patients with ST-segment elevation myocardial infarction (STEMI), 5412 (27.2%) patients with NSTEMI and 11,216 (56.3%) patients with unstable angina (UA). The frequency of prasugrel use at discharge was highest in STEMI and lowest in UA patients, 27.3% versus 22.2% versus 18.9% (p < 0.001). Use of prasugrel vs clopidogrel was associated with a lower rate of MACE in STEMI, NSTEMI, or UA at 1 year, but the differences were attenuated for all groups except for patients with UA (adjusted HR 0.81, 95% CI 0.69–0.94, p = 0.006) after propensity adjusted analysis. After adjustment, there was no difference in bleeding risk between prasugrel and clopidogrel for all groups at 1 year. STEMI patients were more likely to receive prasugrel compared to NSTEMI and UA patients. Prasugrel was associated with reduced adverse outcomes compared with clopidogrel in unadjusted analyses, findings that were largely attenuated upon adjustment and suggest preferential use of prasugrel in low vs high risk patients.

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Funding

The PROMETHEUS study was sponsored and funded by Daiichi Sankyo, Inc. and Eli Lilly and Company.

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Authors and Affiliations

  1. Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Zhen Ge, Usman Baber, Bimmer E. Claessen, Jaya Chandrasekhar, Rishi Chandiramani, Samantha Sartori & George Dangas

  2. Division of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China

    Zhen Ge

  3. Geisel School of Medicine Dartmouth, Lebanon, NH, USA

    Shawn X. Li

  4. Mount Sinai Hospital, New York, NY, USA

    Annapoorna S. Kini

  5. The Duke Clinical Research Institute, Durham, NC, USA

    Sunil V. Rao

  6. Christiana Care Health System, Newark, DE, USA

    Sandra Weiss

  7. Cedars-Sinai Heart Institute, Los Angeles, CA, USA

    Timothy D. Henry

  8. Cleveland Clinic, Cleveland, OH, USA

    Samir Kapadia

  9. Intermountain Heart Institute, Salt-Lake city, UT, USA

    Brent Muhlestein

  10. Minneapolis Heart Institute, Minneapolis, MN, USA

    Craig Strauss

  11. University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Catalin Toma

  12. Aurora Cardiovascular Services, Milwaukee, WI, USA

    Anthony DeFranco

  13. Eli Lilly and Company, Indianapolis, IN, USA

    Mark B. Effron & Stuart Keller

  14. Ochsner Medical Center, John Ochsner Heart and Vascular Institute, New Orleans, LA, USA

    Mark B. Effron

  15. Daiichi Sankyo, Inc., Basking Ridge, NJ, USA

    Brian A. Baker

  16. London School of Hygiene and Tropical Medicine, London, UK

    Stuart Pocock

  17. The Zena and Michael A. Wiener Cardiovascular Institute, The Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY, 10029-6574, USA

    Roxana Mehran

Authors
  1. Zhen Ge
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  2. Usman Baber
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  3. Bimmer E. Claessen
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  4. Jaya Chandrasekhar
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  5. Rishi Chandiramani
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  6. Shawn X. Li
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  7. Samantha Sartori
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  8. Annapoorna S. Kini
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  9. Sunil V. Rao
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  10. Sandra Weiss
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  11. Timothy D. Henry
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  12. Samir Kapadia
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  13. Brent Muhlestein
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  14. Craig Strauss
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  15. Catalin Toma
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  16. Anthony DeFranco
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  17. Mark B. Effron
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  18. Stuart Keller
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  19. Brian A. Baker
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  20. Stuart Pocock
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  21. George Dangas
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  22. Roxana Mehran
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Corresponding author

Correspondence to Roxana Mehran.

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Conflicts of interest

We have the following financial disclosures to report: Dr. Mehran has received institutional grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi, and Eli Lilly and Company/Daiichi Sankyo; and is a consultant to Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, Janssen Pharmaceuticals, Regado Biosciences, Maya Medical, Merck & Co., and The Medicines Company. Dr. Kini serves on the speaker’s bureau of the ACC and has received consulting fees from WebMD. Dr. Henry has received research grant support from Eli Lilly and company, and Daiichi Sankyo. Mr. Keller is employed by Eli Lilly and Company and Dr. Effron is a shareholder and retiree of Eli Lilly and Company. Dr. Baker is employed by Daiichi Sankyo, Inc. All other authors report no relevant conflicts of interest.

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Ge, Z., Baber, U., Claessen, B.E. et al. Associations between use of prasugrel vs clopidogrel and outcomes by type of acute coronary syndrome: an analysis from the PROMETHEUS registry. J Thromb Thrombolysis 48, 42–51 (2019). https://doi.org/10.1007/s11239-019-01842-9

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  • DOI: https://doi.org/10.1007/s11239-019-01842-9

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