[Skip to Navigation]
Original Investigation
March 31, 2021

Efficacy and Safety of Revacept, a Novel Lesion-Directed Competitive Antagonist to Platelet Glycoprotein VI, in Patients Undergoing Elective Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: The Randomized, Double-blind, Placebo-Controlled ISAR-PLASTER Phase 2 Trial

Author Affiliations
  • 1Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technical University of Munich, Munich, Germany
  • 2Department of Cardiology, Medizinische Klinik und Poliklinik I, Munich University Clinic, Ludwig-Maximilian University of Munich, Munich, Germany
  • 3German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
  • 4Medizinische Klinik und Poliklinik Innere Medizin I, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
  • 5Privatklinik Lauterbacher Mühle am Ostersee, Iffeldorf, Germany
  • 6Department of Cardiology, University Medical Center Mainz, Mainz, Germany
  • 7German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Germany
  • 8Medizinische Klinik III–Kardiologie und Angiologie, Eberhard Karls University of Tübingen, Tübingen, Germany
  • 9Institut für Laboratoriumsmedizin, Deutsches Herzzentrum München, Technical University of Munich, Munich, Germany
  • 10Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Kardiologie, Berlin, Germany
  • 11German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany
  • 12Charité-Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Kardiologie, Campus Virchow-Klinikum, Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany
  • 13Cardiology Division, Department of Medicine III, Johann Wolfgang Goethe University, Frankfurt, Germany
  • 14Institute of Medical Informatics, Statistics and Epidemiology, Technical University of Munich School of Medicine, Munich, Germany
  • 15Institute of General Practice and Health Services Research, Technical University of Munich School of Medicine, Munich, Germany
JAMA Cardiol. 2021;6(7):753-761. doi:10.1001/jamacardio.2021.0475
Key Points

Question  Does the addition of revacept, a novel platelet glycoprotein VI antagonist, in addition to currently recommended antithrombotic therapy in the setting of percutaneous coronary intervention (PCI) in patients with stable ischemic heart disease (SIHD) have an effect on the myocardial injury rate?

Findings  In this phase 2 randomized clinical trial, revacept did not reduce myocardial injury in patients with SIHD undergoing PCI. There were few bleeding events and no significant differences between treatment arms, and the 160-mg dose of revacept had a small but statistically significant effect on collagen-induced but not adenosine 5′-diphosphate–induced platelet aggregation.

Meaning  In patients with SIHD undergoing PCI, addition of revacept to standard antithrombotic therapy does not reduce the incidence of myocardial injury.

Abstract

Importance  The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant.

Objective  To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI.

Design, Setting, and Participants  A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI).

Interventions  Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy.

Main Outcomes and Measures  The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days.

Results  Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5′-diphosphate–induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36).

Conclusions and Relevance  Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms.

Trial Registration  ClinicalTrials.gov Identifier: NCT03312855

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    Still have interests in GPVI inhibitor
    Shinya Goto, MD, PhD | Tokai University School of Medicine
    I have read the paper by Mayer K, et al with special interests. We expected GPVI inhibition might results with reduced risk of thrombosis without increase in bleeding complication because GPVI deficient patients did not experienced serious bleeding complication. Specific behavior of platelet interaction with collagen and von Willebrand factor under blood flow conditions (Circulation 2002, 106(2):266-72) as published previously also suggest GPVI as interesting target. I would expect larger sized hypothesis testing clinical trials in the future.
    CONFLICT OF INTEREST: Associate Editor for Circulation
    ×