Adjusting antiplatelet therapy on the basis of platelet function doesn’t confer any significant clinical benefits over a course of standard antiplatelet therapy for patients undergoing coronary stenting.
By the end of 1 year, about a third of patients in each group had died or experienced a heart attack, stent thrombosis, cerebrovascular accident, or urgent revascularization, Dr. Gilles Montalescot and his colleagues reported simultaneously at the annual scientific sessions of the American Heart Association and in the Nov. 4 issue of the New England Journal of Medicine (2012 [doi:10.1056/NEJMoa12099979]).
"We observed no hint of improvement in ischemic outcomes and no better safety outcomes with a strategy of monitoring and drug adjustment as compared with a conventional strategy," wrote Dr. Montalescot of the University Pierre and Marie Curie, Paris, and his co-investigators in the ARCTIC trial (Assessment by a Double Randomization of a Conventional Antiplatelet Strategy vs. a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption vs. Continuation 1 Year After Stenting).
ARCTIC comprised 2,440 patients about to undergo coronary stenting. They were randomized to either conventional antiplatelet therapy, or to flexible antiplatelet treatment guided by platelet-function monitoring.
The patients were a mean of 63 years old; about 80% were men. About a quarter (27%) presented with an acute coronary syndrome without ST-segment elevation.
At the time of stenting, patients in the monitoring group underwent platelet function measuring for both aspirin and P2Y12 inhibitors. (The P2Y12 inhibitors clopidogrel and prasugrel, both thienopyridines, were used in the study.) These assays were repeated 2-4 weeks after stenting, and drug therapy was adjusted according to the results.
If the initial assay indicated aspirin reactivity, these patients received an aspirin bolus before stenting. If reactivity with clopidogrel was detected, the patient received either glycoprotein IIb/IIIa inhibitors and a loading dose of at least 600 mg clopidogrel, or a loading dose of 60 mg prasugrel, followed by a daily maintenance dose of 150 mg clopidogrel or 10 mg prasugrel.
At the 2- to 4-week follow-up visit, patients who showed high platelet reactivity with clopidogrel were switched to 10 mg prasugrel or had a 75-mg increase in their daily clopidogrel.
If, during treatment, patients had low platelet reactivity with thienopyridine, they were switched to daily clopidogrel at 75 mg if they were already getting 10 mg prasugrel or 150 mg clopidogrel.
Patients in the standard therapy group received the stents without any platelet function tests. The use of GP IIb/IIIa inhibitors was left up to the treating physicians.
Before stenting, 34% of the monitoring group had high clopidogrel platelet reactivity; 80% of those received the clopidogrel bolus and 3% the additional prasugrel. High aspirin reactivity was seen in 8%; of those, 85% had the additional aspirin dose.
At the follow-up visit, 16% of the monitoring group showed high platelet reactivity to thienopyridine; 43% of those then received an increase in their maintenance clopidogrel dose. A total of 4% of the monitoring group showed aspirin reactivity at the follow-up visit; 46% of these received an increase in their maintenance dose.
At 1 year after stenting, the primary composite end point had occurred in 35% of the monitoring group and 31% of the standard therapy group, a nonsignificant difference. There were no significant between-group differences when the component end points were individually examined. Bleeding rates were less than 5% and similar in both groups.
The study was largely sponsored by Allies in Cardiovascular Trials Initiatives and Organized Networks, and included funding from Sanofi-Aventis, Cordis, Medtronic, and Boston Scientific.
Dr. Montalescot disclosed that he is a consultant with Atrium, Bayer, and Bristol-Myers Squibb. Several of the coauthors reported financial relationships with multiple pharmaceutical and device companies.