Safety profile and tolerability of intravenous AR-C69931MX, a new antiplatelet drug, in unstable angina pectoris and non-Q-wave myocardial infarction
2002 (English)In: Clinical Therapeutics, ISSN 0149-2918, Vol. 24, no 5, 752-765 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2002. Vol. 24, no 5, 752-765 p.
Adjunctive therapy, Atherosclerotic plaque, Hemodynamic tolerance, Ischemic heart disease, Platelet aggregation, Unstable coronary artery disease
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-46980DOI: 10.1016/S0149-2918(02)85149-9OAI: oai:DiVA.org:liu-46980DiVA: diva2:267876