European Society of Cardiology
European Society of Cardiology
Source/Disclosures
Source:

Massberg S, et al. Latest Findings in Coronary Artery Disease (Chronic). Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2020 (virtual meeting).

Disclosures: The study was funded by the German Center for Cardiovascular Research. Massberg reports he received funding from the German Center for Cardiovascular Research.
September 04, 2020
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Novel GPVI inhibitor may lower bleeding risk during PCI for CAD

Source/Disclosures
Source:

Massberg S, et al. Latest Findings in Coronary Artery Disease (Chronic). Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2020 (virtual meeting).

Disclosures: The study was funded by the German Center for Cardiovascular Research. Massberg reports he received funding from the German Center for Cardiovascular Research.
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A higher dose of a glycoprotein VI inhibitor in patients with CAD who underwent PCI resulted in more pronounced platelet inhibition without increasing bleeding risk, researchers found in the ISAR PLASTER trial.

The 160 mg dose of the soluble dimeric glycoprotein VI-Fc fusion protein (Revacept, AdvanceCor), which was given on top of standard dual antiplatelet therapy, did not significantly affect myocardial injury in patients with chronic coronary syndrome at low ischemic risk, and better inhibited platelets without raising bleeding risk compared with a 80 mg dose of the drug and placebo, according to the trial presented at the European Society of Cardiology Congress.

Source: Adobe Stock.

“This novel therapeutic concept should be further explored in clinical scenarios with a high ischemic risk,” Steffen Massberg, MD, professor of cardiology and director of the department of cardiology at University Clinic Munich at Ludwig-Maximilians University, said during the presentation.

“The development of drugs that block platelets without increasing bleeds is a major medical need,” Massberg said during the presentation. “There is a novel drug, so-called GPVI inhibitors that actually might meet this requirement.”

In this multicenter, randomized, double-blind trial, researchers analyzed data from 334 patients with chronic coronary syndromes with an indication for PCI who were receiving dual antiplatelet therapy and had a normal high-sensitivity cardiac troponin T level.

Patients were assigned 160 mg of the glycoprotein VI (GPVI) inhibitor (n = 120; mean age, 67 years; 32% women), 80 mg of the GPVI inhibitor (n = 121; mean age, 67 years; 20% women) or placebo (n = 93; mean age, 68 years; 20% women). All treatments were administered intravenously before PCI and were added on top of standard dual antiplatelet therapy.

“Interestingly, GPVI plays an important role in atherothrombosis, but it is not involved, at least not relevantly involved, in hemostasis, making it an interesting candidate for inhibition,” Massberg said during the presentation. “Revacept is a form of GPVI that binds to exposed collagen. It does not bind to platelets for platelet inhibition, but it acts as sort of a lesion-directed competitive inhibitor to platelet-exposed GPVI, sort of like a lesional plaster.”

The primary endpoint was death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin T five or more times the upper limit of normal at 48 hours. Secondary endpoints included peak high-sensitivity cardiac troponin T at 48 hours and MACE at 30 days, defined as all-cause mortality, MI, stroke, PCI-related MI, urgent coronary revascularization and definite stent thrombosis. The safety endpoint was Bleeding Academic Research Consortium type 2 bleeding or higher at 30 days.

At 48 hours, collagen-induced platelet aggregation was significantly reduced in patients assigned 160 mg of the GPVI inhibitor compared with the other groups (P = .018). Minimal difference was observed in the three groups regarding adenosine diphosphate-induced platelet aggregation (P = .11).

Death or myocardial injury occurred in 24.3% of the entire cohort. This did not significantly differ in the three study groups (P = .975).

“Since there was only one death in the whole cohort, the result of the primary endpoint is practically driven by the rise in troponin T,” Massberg said during the presentation.

There was no difference in high-sensitivity cardiac troponin T in the patients assigned 160 mg of the GPVI inhibitor (28 ng/L), those assigned 80 mg of the GPVI inhibitor (31.5 ng/L) and patients assigned placebo (32 ng/L; P = .443).

The rate of MACE at 30 days was 2.5% for the entire cohort, with no significant difference between the groups (P = .91). When individual components of MACE were assessed, this event rate was primarily driven by MI, which also did not significantly differ between the groups. At 30 days, there was only one death, of a patient in the GPVI inhibitor 80 mg group.

Safety at 30 days were similar in the three groups (P = .362).

“It was very surprising and interesting to see that although Revacept, particularly the high dose, blocked patients more efficiently than placebo, this did not translate into an increase in bleeding complications,” Massberg said.