Conventional antiplatelet drugs such as aspirin or clopidogrel act throughout the body. In contrast, GPVI-Fc attaches itself to the injured blood vessels like a plaster and prevents platelets from binding there. Blood clotting is therefore only inhibited locally and not throughout the entire body. This could reduce the risk of bleeding, a dangerous complication of current antiplatelet drugs.

Prof. Steffen Massberg from LMU Klinikum München and Prof. Adnan Kastrati from Deutsches Herzzentrum München have now tested GPVI-Fc for the first time during a cardiac catheterization procedure as part of the ISAR-PLASTER clinical trial. During such an intervention, it is investigated whether coronary arteries narrowed by deposits need to be widened so that the heart receives enough blood again. If the constrictions have to be removed, 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 swept away with the blood flow, they can block important vessels and cause a heart attack.

Patients are therefore given antiplatelet medication during the procedure if the vessels need to be dilated. Although this can reduce the rate of heart attacks 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 platelet inhibitors clopidogrel and aspirin are taken as tablets, and it takes three to four hours for them to enter the bloodstream via the intestine and take effect there. In addition, clopidogrel is not effective enough in 20 percent of patients."

The scientists wanted to know whether GPVI-Fc could close this time and individual therapeutic gap, thereby reducing the heart attack rate without increasing the risk of bleeding. In addition to targeted anticoagulation, the innovative platelet inhibitor has another advantage: doctors can inject it directly into the patient's blood, meaning it can take effect very quickly. 334 patients with stable coronary heart disease took part in the study, which was conducted at nine centers. GPVI-Fc was administered in addition to the established antiplatelet drugs.

"GPVI-Fc is safe and there was no increase in bleeding complications," says Massberg, summarizing the results of the study. In the blood of the study participants, the researchers were able to prove that GPVI-Fc with a dosage of 160 mg also develops its anticoagulant effect in patients as specifically as observed in previous studies in healthy volunteers. Heart attacks during and shortly after the catheter procedure were very rare overall and could not be further reduced by the administration of GPVI-Fc in addition to conventional antiplatelet drugs.

Massberg suspects why the researchers were unable to see any effect on the heart attack rate: "As this was a phase 2 clinical trial, the novel antiplatelet agent was tested in low-risk patients. There are generally fewer heart attacks in this patient group". In a phase 3 study, she therefore wanted to investigate how GPVI-Fc works in patients who undergo vasodilatation as part of a heart attack. In this group, it is more likely to observe an effect of GPVI-Fc on the heart attack rate

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