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Revacept therapy (80 mg or 160 mg) did not reduce myocardial injury in patients with stable ischemic heart disease who underwent percutaneous coronary intervention (PCI), according to research results published in JAMA Cardiology.
For the first time, researchers sought to evaluate the efficacy and safety of 2 revacept doses — a novel, lesion-directed antithrombotic drug — in patients with stable ischemic heart disease who underwent elective PCI plus standard dual antiplatelet therapy. ISAR-PLASTER (ClinicalTrials.gov Identifier NCT03312855) was a multicenter, randomized, double-blind, investigator-initiated trial across 9 study sites in Germany that included adults with stable ischemic heart disease, normal high-sensitivity cardiac troponin T (hsTnT) levels, and angiographic evidence of coronary artery disease (CAD).
Eligible patients were randomly assigned to receive either placebo, revacept 80 mg, or revacept 160 mg. The primary study endpoint was a composite of death or myocardial injury, defined as an increase in hsTnT value to at least 5 times the upper limit of normal within 48 hours of randomization.
Secondary endpoints included peak hsTnT within 48 hours of randomization, all-cause mortality, myocardial infarction, PCI-related myocardial infarction, stroke, definite stent thrombosis, and urgent coronary revascularization within 30 days.
The total cohort included 334 patients who were randomly assigned to the study groups.
At 48 hours following randomization, 24.3% of patients experienced the combined primary endpoint, with no significant differences between the revacept and placebo groups (24.4% of the revacept 160 mg group and 25% of the revacept 80 mg group). There were no statistically significant differences in incidence of the primary endpoint between patients with and without clopidogrel loading before PCI.
With 48 hours of randomization, median peak hsTnT was 31.5 ng/L and 28.0 ng/L in the revacept 80 and 160 mg groups, respectively, compared with 32.0 ng/L in the placebo group. Four patients demonstrated an hsTnT increase of at least 70 times the upper limit of normal with 48 hours of randomization.
In total, 2.7% of the patients in the entire cohort experienced a composite of all-cause death, myocardial infarction, stroke, or urgent revascularization within 30 days of randomization, without a significant difference between the treatment and placebo groups (2.5% revacept 160 mg, 3.3% revacept 80 mg, and 2.2% placebo).
Key secondary safety endpoint of Bleeding Academic Research Consortium (BARC) type 2 to 5 bleeding incidences differed marginally between groups in the modified intention-to-treat population: 5%, 5.9%, and 8.6% in the revacept 160 mg, revacept 80 mg, and placebo groups, respectively. All events were recorded within 2 days of randomization. BARC type 1 bleeding was noted in 12.5%, 10.9%, and 5.4% of each of these groups.
The 48-hour laboratory parameters were not significantly different between groups nor were ECG parameters — although a slight but significant prolongation of the QTc interval was noted in the revacept groups (revacept 160 mg, median, 423 milliseconds; revacept 80 mg, median, 421 milliseconds; placebo, median, 414 milliseconds).
Revacept therapy significantly reduced platelet aggregation in response to collagen in 93 µg/mL and 253 µg/mL concentrations compared with placebo.
Study limitations include the enrollment of patients who were at a very low risk of ischemic events and the study itself not being powered for hard clinical endpoints.
“In this first-in-class phase 2 trial on a competitive GPVI inhibitor, revacept did not reduce myocardial injury in patients with [stable ischemic heart disease] undergoing PCI,” the researchers concluded. “There were few bleeding events and no significant differences between treatment arms.”
Disclosure: This clinical trial was supported by advanceCOR GmbH. Please see the original reference for a full list of disclosures.
Reference
Mayer K, Hein-Rothweiler R, Schüpke S, et al. 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. JAMA Cardiol. Published online March 31, 2021. doi:10.1001/jamacardio.2021.0475
