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

Abstract

IMPORTANCEThe 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 PARTICIPANTSA 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 MEASURESThe 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. RESULTSOf 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 RELEVANCERevacept 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.

Platelets, Thromboinflammation and Neurovascular Disease

“…Even dual antiplatelet therapy has been applied in clinical trials (115). However, studies have reported that antiplatelet therapy increases the risk of bleeding and is positively associated with duration of therapy (116). Early and short-term dual antiplatelet therapy for minor stroke or high-risk transient ischemic attack (TIA) has been suggested by the clinical guidelines (116).…”

Factors Associated with Platelet Activation-Recent Pharmaceutical Approaches

“…However, the results of the recently reported ISAR-PLASTER phase 2 trial in 334 patients undergoing elective percutaneous revascularization for coronary artery disease were neutral, demonstrating no differences between the two dosing regimens of revacept compared to placebo regarding the composite endpoint of death or high-sensitivity cardiac troponin increase to at least five times the upper limit of normal within 48 h from randomization, despite the significant reduction of collagen-induced platelet aggregation in the high-dose revacept arm. Bleeding events did not differ significantly between the groups [ 206 ]. Another trial of revacept in patients with symptomatic carotid artery disease is currently ongoing [ 207 ], with its results being eagerly awaited.…”

Chronic inflammation in atherosclerosis—The CD40L/CD40 axis belongs to dendritic cells and T cells, not platelets

“…| 5 LANGER a phase 2 randomized clinical trial with patients undergoing elective percutaneous coronary intervention (PCI) for stable ischemic heart disease. 15 The authors analyzed a short-term endpoint of a composite of death or myocardial injury, whereby Revacept ® had no significant effect. As expected, bleeding was not increased and further studies are required to finally evaluate the value of this approach for CV patients.…”