ANTARCTIC results chill enthusiasm for platelet monitoring

ROME – Measuring platelet function in order to tailor antiplatelet therapy in elderly patients undergoing percutaneous coronary intervention for acute coronary syndromes did not improve their clinical outcomes in the randomized ANTARCTIC trial, Gilles Montalescot, MD, reported at the annual congress of the European Society of Cardiology.

“We found absolutely no benefit for this strategy of adjustment of antiplatelet therapy based upon platelet function testing. The study was completely neutral on all types of endpoints, ischemic as well as bleeding,” said Dr. Montalescot, professor of cardiology at the University of Paris VI and director of the cardiac care unit at Pitié-Salpêtrière Hospital.

Dr. Gilles Montalescot

This was a disappointing result in what was the largest-ever randomized clinical trial involving PCI in elderly patients, he said. This was a high-risk population, not only by virtue of everyone being over age 75 years, but because they all presented with ACS. Indeed, one-third of ANTARCTIC participants underwent primary PCI for ST-segment elevation myocardial infarction.

ANTARCTIC (Assessment of a Normal Versus Tailored Dose of Prasugrel After Stenting in Patients Aged Over 75 Years to Reduce the Composite of Bleeding, Stent Thrombosis, and Ischemic Complications) was carried out as a follow-up to the earlier ARCTIC randomized trial, also conducted by Dr. Montalescot and his coinvestigators. Like ANTARCTIC, ARCTIC, too, showed no clinical benefit for platelet function testing in order to adjust antiplatelet therapy (N Engl J Med. 2012;367:2100-9). At the time, ARCTIC’s critics argued that this individualized strategy didn’t achieve the expected improved outcomes because the trial was conducted in low-risk, stable patients undergoing elective scheduled PCI. In contrast, if there was ever a high-risk population in which platelet function testing and tailored antiplatelet therapy should work, it was in the very high-risk ANTARCTIC population, he said.

ANTARCTIC included 877 elderly patients undergoing urgent PCI for ACS who were placed on low-dose aspirin and randomized to standard antiplatelet therapy with prasugrel (Effient) at 5 mg/day, the European approved dose for long-term maintenance therapy in elderly patients, or to tailored antiplatelet therapy.

Patients in the tailored therapy arm received prasugrel at 5 mg/day for the first 14 days, then underwent platelet function testing with the VerifyNow P2Y12 system. If they demonstrated high on-drug platelet activity, defined as at least 208 P2Y12 reaction units (PRU), their prasugrel was bumped up to 10 mg/day. If their PRU measurement was in what is considered the optimal range for quelling ischemia without promoting bleeding – that is, less than 208 but more than 85 PRU – they remained on prasugrel at 5 mg/day. And if they scored less than 85 PRU, exposing them to excess bleeding risk due to high suppression of platelets, they were switched to clopidogrel (Plavix) at 75 mg/day, a less potent antiplatelet regimen.

Two weeks after their first platelet function measurement, participants in the tailored therapy arm returned for a second round of platelet activity testing, with their antiplatelet regimen once again being adjusted on the basis of the results.

The primary study endpoint was net clinical benefit over a 12-month follow-up period. This was defined as the composite of cardiovascular death, MI, stroke, urgent revascularization, stent thrombosis, and Bleeding Academic Research Consortium (BARC) types 2, 3, or 5. This composite endpoint occurred in 27.6% of the platelet monitoring group and a near-identical 27.8% of conventionally managed patients.

Of note, 42% of patients in the actively monitored group were within the target platelet inhibition range when tested 14 days into the study. At study’s end, 55% of patients remained on prasugrel at 5 mg/day, 39% were on clopidogrel at 75 mg/day, and less than 4% were on prasugrel at 10 mg/day. Thus, most patients who underwent a dose adjustment on the basis of their VerifyNow results were downgraded to a less-potent antiplatelet regimen. Very few required enhanced platelet suppression in the form of 10 mg/day of prasugrel.

“Platelet function monitoring is difficult to use. Patients have to come back twice to be monitored. It’s costly. It’s time consuming. And platelet function monitoring clearly does not help,” the cardiologist said.

The ANTARCTIC results will likely lead to a revision of the American and European guidelines, which currently give a class IIb/level of evidence C recommendation for platelet function testing in high-risk situations.

“There is a huge literature showing that platelet reactivity affects clinical outcomes,” Dr. Montalescot continued. “One hypothesis now is that platelet reactivity may be only a marker of risk; you can modify it, but that has no impact on patient outcomes. We may be in the same situation here as with HDL cholesterol, for example.”