Platelet Function Testing to Guide Treatment Does Not Benefit Elderly ACS Patients: ANTARCTIC

ROME, Italy—In elderly patients treated with prasugrel after undergoing stenting for ACS, use of platelet function testing to either adjust their dose or switch them to clopidogrel had no effect on ischemic or bleeding outcomes in the randomized ANTARCTIC trial.

The findings, presented here by Gilles Montalescot, MD, PhD (Hôpital Pitié-Salpêtrière, Paris, France), at the European Society of Cardiology Congress 2016 and published simultaneously online in the Lancet, are consistent with those from prior studies enrolling stable patients, including ARCTIC, a trial that was criticized for including lower-risk patients undergoing elective PCI and mostly using clopidogrel as the P2Y12 inhibitor.

“ANTARCTIC after ARCTIC confirms failure to improve the prognosis of patients by monitoring platelet function to individualize antiplatelet therapy,” Montalescot said at a press conference. “And this time we can say that failure is not related to the risk level of the population or to the type of P2Y12 antagonist.”

Commenting on the trial to TCTMD, American College of Cardiology President Richard Chazal, MD (Lee Memorial Health System, Fort Myers, FL), said the results are “very helpful” in that they provide data to inform clinicians as to whether they should continue using platelet function testing.

He pointed out that current guidelines include a class III recommendation against routinely performing platelet function testing in patients undergoing PCI because of a lack of benefit, although there is a class IIb recommendation stating that it may be considered in high-risk patients. 

ANTARCTIC “would call that into question, because this was a high-risk population,” Chazal said, noting that all patients were at least 75 years old and had ACS. It’s “something that our guidelines task force will have to look at moving forward.”

Chazal added that it’s not uncommon for physicians to use platelet function testing to select antiplatelet drugs or adjust dosing in high-risk patients.

But “particularly in an era where we’re trying to provide value-based care,” he said, “adding yet another step that involves some resources and cost is fairly hard to justify if we don’t have some data to support its use.”

No Net Clinical Benefit

Conducted at 35 French centers, ANTARCTIC included 877 elderly patients who underwent urgent PCI for ACS. About half had NSTEMI (48%), 34% had STEMI, and 18% had unstable angina. Patients were randomized to either receive prasugrel 5 mg/day (Effient, Eli Lilly) without platelet function testing or a tailored prasugrel dose. In the latter group, all patients started on the 5-mg dose but would be switched to clopidogrel 75 mg/day if platelet function testing showed a P2Y12 reactivity unit (PRU) level of 85 or lower or would have their prasugrel dose increased to 10 mg/day if the PRU was 208 or higher.

Ultimately, 92.8% of patients in the control group remained treated with prasugrel 5 mg, while a minority had their P2Y12 inhibitor stopped or were switched to clopidogrel or higher-dose prasugrel. In the testing group, 55.2% remained on prasugrel 5 mg, 39.3% started taking clopidogrel, 3.7% had their prasugrel dose increased, and 1.8% stopped taking a P2Y12 inhibitor.

Those changes in treatment, however, had no effect on the primary endpoint of net clinical benefit at 1 year, which incorporated BARC type 2, 3, or 5 bleeding and MACE (cardiovascular death, MI, urgent revascularization, stent thrombosis, or stroke); 28% of patients in each group had an event (HR 1.00; 95% CI 0.78-1.29). The findings were similar when the ischemic and bleeding outcomes were analyzed separately.

Why It Failed

In an editorial accompanying the Lancet paper, Dirk Sibbing, MD, and Steffen Massberg, MD (both German Center for Cardiovascular Research, Munich, Germany), point out some issues to consider when looking for what might explain the neutral trial result.

First, they say, the trial was designed with an initial strategy of low-dose prasugrel for both groups and the most frequent change in the testing group was a switch to clopidogrel. That’s important to note, Sibbing and Massberg stress, because prior trials have shown similar outcomes with low-dose prasugrel and clopidogrel in elderly patients, regardless of whether platelet function testing is done.

Second, the editorialists point out that previous pharmacodynamics studies have revealed small differences between low-dose prasugrel and clopidogrel at the level of platelet inhibition that might not be sufficient to lead to significant changes in outcomes.

“The aim of the ANTARCTIC study was to treat patients towards a therapeutic window of platelet inhibition, with a default strategy of low-dose prasugrel,” they write. “Because this strategy did not provide net clinical benefit, the reasons for which might be manifold, future studies will have to test distinct approaches.”

Sources:

•  Cayla G, Cuisset T, Silvain J, et al. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomized controlled superiority trial. Lancet. 2016;Epub ahead of print.
•  Sibbing D, Massberg S. Antiplatelet strategies in elderly people: still a long way to go. Lancet. 2016;Epub ahead of print.

Disclosures:

• The study was led by the academic research organization Allies in Cardiovascular Trials, Initiatives, and Organized Networks (ACTION), sponsored by the Assistance Publique des Hôpitaux de Paris, and funded by Eli Lilly, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.
• Montalescot reports multiple relationships with industry.
• Sibbing reports receiving speak fees and honoraria for consulting from Eli Lilly, Daiichi Sankyo, Bayer Vital, Pfizer, AstraZeneca, and Roche Diagnostics and research grants from Roche Diagnostics.
• Massberg and Chazal report no relevant conflicts of interest.

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