Safety profile and tolerability of intravenous AR-C69931MX, a new antiplatelet drug, in unstable angina pectoris and non-Q-wave myocardial infarction

• Background: Thrombin generation and platelet aggregation in the disrupted atherosclerotic plaque are the major reasons for thrombus formation associated with acute coronary events. AR-C69931MX is a new agent that inhibits adenosine diphosphate-induced platelet aggregation by antagonism of the P2T purinoceptor. Objective: This study assessed the safety profile, tolerability, and plasma concentrations at steady state of intravenous AR-C69931MX in patients with unstable angina pectoris or non-Q-wave myocardial infarction (MI). Methods: This was a Phase II, multicenter, double-blind, randomized, placebo-controlled trial. Patients with unstable angina or non-Q-wave MI were randomized to a 72-hour infusion of AR-C69931MX or placebo as adjunctive therapy to aspirin and low-molecular-weight heparin. Other treatment was at the discretion of the local investigator. Outcomes were assessed at 30 days. Results: Ninety-four patients were randomized and 91 received treatment (45 AR-C69931MX, 46 placebo). Plasma concentrations of AR-C69931MX were within the expected range, there were no signs of accumulation, and interindividual variability in clearance was low. Four patients receiving AR-C69931MX discontinued treatment due to minor bleeding events, and 5 patients receiving placebo discontinued treatment due to other adverse events or deterioration in their condition. No serious bleeding events were seen during treatment. The incidence of =1 episode of minor bleeding was slightly higher in patients receiving AR-C69931MX compared with those receiving placebo (38% vs 26%, respectively). The drug was well tolerated hemodynamically, and there were no significant changes in other laboratory values between groups. Conclusions: As adjunctive therapy to aspirin and low-molecular-weight heparin in patients with unstable angina or non-Q-wave MI, intravenous AR-C69931MX was well tolerated, with no difference in the incidence of serious adverse events compared with placebo.

Keyword

Adjunctive therapy

Atherosclerotic plaque

Hemodynamic tolerance

Ischemic heart disease

Platelet aggregation

Unstable coronary artery disease

MEDICINE

MEDICIN

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ref (subject category)

art (subject category)