Conventional antithrombotic drugs such as aspirin or clopidogrel act systemically and block platelets everywhere in the circulation. In contrast, Revacept attaches like a plaster to injured blood vessels and prevents platelets from binding. Blood clotting is therefore only inhibited locally and not in the whole body. This could reduce the risk of bleeding, a dangerous complication associated with antithrombotic drugs currently in use.
Prof. Steffen Massberg from LMU Klinikum München and Prof. Adnan Kastrati from Deutsches Herzzentrum München have now tested Revacept for the first time during a cardiac catheterisation as part of the ISAR-PLASTER clinical trial. During such an intervention, doctors examine whether coronary vessels narrowed by atherosclerotic deposits have to be widened so that the heart receives sufficient blood supply. If they have to treat the narrowing by stent implantation, there is a risk that the deposits in the vessels will rupture. This attracts blood platelets, which clump together and form clots. If these are washed away with the bloodstream, they can block essential vessels downstream and cause a periprocedural heart attack.
To prevent this from happening, patients are receiving antithrombotic drugs during the procedure when the vessels have to be widened. Although this can reduce the heart attack rate during and shortly after the catheter procedure, they still occur in some patients. According to Massberg, there are two reasons for this: "The currently administered antiplatelet drugs clopidogrel and aspirin are taken as tablets, and it takes three to four hours for them to enter the blood via the intestines and take effect there. Besides, clopidogrel does not work adequately in up to 20 percent of patients."
Closing therapeutic gaps
The scientists wanted to know whether Revacept can close this temporal and individual therapeutic gap so that the heart attack rate decreases without increasing bleeding risk. This is because, in addition to targeted antithrombotic action, the innovative antiplatelet drug has another advantage: doctors can inject it directly into the patients' blood so that it can take effect very quickly. 334 patients with stable coronary heart disease took part in the study conducted at nine centres. Revacept was administered in addition to the conventional antiplatelet drugs.
Safe, but not effective for low-risk heart attacks
"Revacept is safe; bleeding complications did not increase," Massberg summarises the results of the study. In the study participants' blood, the researchers proved that Revacept with a dosage of 160 mg also unfolded its antithrombotic effect in patients as specifically as observed in previous studies in healthy volunteers. During and shortly after catheterisation, the rate of heart attacks overall was very low, and the administration of Revacept in addition to conventional antiplatelet drugs could not further reduce it.
Massberg suspects why the researchers did not see any effect on heart attack rates: "Since this was a phase 2 clinical trial, we tested the novel antiplatelet agent in low-risk patients. In this low-risk setting, there are generally fewer heart attacks." In a phase 3 trial, he said, he would investigate how Revacept works in patients who receive stent implantation as part of a heart attack. In this group, it is more likely to see an effect of Revacept on heart attack rates.
Scientific contact: Professor Steffen Massberg, Director of the Medical Clinic and Policlinic I, LMU Klinikum München, Steffen.Massberg(at)med.uni-muenchen.de
Study: Revacept, a novel inhibitor of platelet adhesion in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention: a randomized, double-blind, placebo-controlled, phase II Trial REVACEPT ISAR-PLASTER
Original publication: 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. Mayer K, Hein-Rothweiler R, Schüpke S, Janisch M, Bernlochner I, Ndrepepa G, Sibbing D, Gori T, Borst O, Holdenrieder S, Kupka D, Petzold T, Bradaric C, Okrojek R, Leistner DM, Trippel TD, Münzel T, Landmesser U, Pieske B, Zeiher AM, Gawaz MP, Hapfelmeier A, Laugwitz KL, Schunkert H, Kastrati A, Massberg S. JAMA Cardiol. 2021 Mar 31. DOI: 10.1001/jamacardio.2021 .0475