麻豆传媒

LOS ANGELES -- Monitoring platelet function in patients undergoing coronary stenting and adjusting antiplatelet therapy accordingly did not improve outcomes, the ARCTIC trial showed.

The rate of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation was not significantly different between patients who had therapy tailored according to platelet reactivity and those who did not (34.6% versus 31.1%, HR 1.13, 95% CI 0.98 to 1.29), according to Gilles Montalescot, MD, PhD, of Pitié-Salpêtrière University Hospital in Paris.

Similarly, there was no difference in the main secondary endpoint -- the rate of stent thrombosis or urgent revascularization (4.9% versus 4.6%, HR 1.06, 95% CI 0.74 to 1.52), he reported at the American Heart Association meeting here. The findings were reported simultaneously online in the New England Journal of Medicine.

The findings are consistent with those from another recent study, GRAVITAS, which failed to show a benefit from more intensive platelet inhibition with a double dose of clopidogrel in patients with high on-treatment platelet reactivity following stenting.

"The main message is that there is no room for systematic platelet function testing in the cath lab," Montalescot said in an interview.

Gordon Tomaselli, MD, from Johns Hopkins University School of Medicine in Baltimore and a past president of the AHA, agreed.

"In terms of its applicability to outcome, I don't think that we're going to be using it routinely in clinical practice to either assess efficacy of thienopyridine platelet inhibitors or to adjust dose because it looks like basically it didn't make much of a difference," he told 麻豆传媒.

The ARCTIC trial included 2,440 patients (median age 63) who were scheduled to undergo coronary stenting with a drug-eluting stent at one of 38 French centers. They were randomized to conventional antiplatelet therapy without measures of platelet function or antiplatelet therapy tailored according to platelet function tests performed before and after the procedure, as well as 2 and 4 weeks later.

The VerifyNow assay was used to measure platelet reactivity for both aspirin and the two P2Y₁₂ inhibitors used in the study, clopidogrel and prasugrel (Effient). Prasugrel was introduced in France during the course of the study.

High platelet reactivity for the aspirin regimen was defined as 550 or more aspirin reaction units. For those taking a thienopyridine, high platelet reactivity was defined as 235 or more platelet reaction units (PRUs), 15% or less inhibition as compared with a baseline measurement of thrombin-receptor-activating-peptide-induced aggregation, or both.

Before stent implantation, patients with high platelet reactivity on aspirin received IV aspirin during the procedure. Those with high platelet reactivity on clopidogrel received glycoprotein IIb/IIIa inhibitors and an additional loading dose of clopidogrel (600 mg or more) or a loading dose of prasugrel (60 mg) before the procedure, followed by a daily maintenance dose of clopidogrel 150 mg or prasugrel 10 mg.

At both 2 and 4 weeks, patients with high platelet reactivity on clopidogrel were switched to prasugrel 10 mg or received a 75-mg increase in the clopidogrel maintenance dose.

Patients who responded to therapy maintained their treatment regimens.

For patients in the control group, the use of antiplatelet therapy was left to the discretion of the treating physicians.

In the group monitored with platelet function testing, high platelet reactivity before stenting was present in 34.5% of patients taking clopidogrel and 7.6% of those taking aspirin, and antiplatelet therapy was adjusted accordingly. Additional adjustments were made upon testing at 2 and 4 weeks.

The enhanced antiplatelet therapy, however, did not improve clinical outcomes. Major and minor bleeding occurred at similar rates in each group.

Despite the lack of an effect on outcomes, Montalescot said that using platelet function testing to adjust antiplatelet therapy should be pursued in future studies. One such study, ANTARCTIC, is ongoing in patients 75 and older.

It is possible, he said, that platelet function testing may have a benefit when using the more potent P2Y₁₂ inhibitors -- like prasugrel and ticagrelor. In ARCTIC, prasugrel was used in only about 10% of the patients.

"There are studies ongoing and we will see more data accumulating before we close the door definitively [on platelet function testing], if we need to close it," Montalescot said.

Tomaselli said that he'd have to see evidence of a large benefit from platelet function testing before incorporating it into clinical practice because it adds expense and can delay treatment.

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