ADAPT-DES: High On-Aspirin Platelet Reactivity Not Related to PCI Outcomes

High on-aspirin platelet reactivity (HAPR) is not commonly seen in patients who undergo successful PCI with a drug-eluting stent, and when it is found it does not seem to have a big impact on clinical outcomes, an ADAPT-DES analysis shows.

HAPR was not associated with 2-year risks of MACE, stent thrombosis, MI, all-cause death, or clinically-relevant bleeding, according to researchers led by Christine Chung, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY).

The study—initially presented at TCT 2016 in Washington, DC, and published online August 15, 2018, ahead of print in the American Heart Journal—is the largest to explore the issue, Chung told TCTMD, noting that prior smaller studies have provided mixed results.

“Obviously it’s not a randomized trial, so we can’t make any definitive conclusions about causality and base treatment recommendations on it, but I think it still really adds more weight to the suggestion that it may be safe to omit aspirin in certain people,” she said.

Chung indicated that the findings serve as a prelude to randomized trials exploring the necessity of aspirin after stent implantation that are expected to report results soon, including GLOBAL LEADERS and TWILIGHT.

Dominick Angiolillo, MD, PhD (University of Florida College of Medicine – Jacksonville), however, cautioned against conflating the suggestive findings of ADAPT-DES with the results that will come out of those trials because of differences in the P2Y12 inhibitors involved in the studies: clopidogrel in ADAPT-DES and ticagrelor (Brilinta; AstraZeneca) in the randomized trials. The two antiplatelets have significant differences in terms of their effects on global platelet function, Angiolillo told TCTMD.

“It’s very early to make any comments to the extent of a need for dropping aspirin until we have data. I think it’s a reasonable approach in patients with atrial fibrillation concomitantly treated with an oral anticoagulant, where we do have some data, and that is now a strategy endorsed by recently reported expert consensus,” he said.

But in the context of PCI in patients without A-fib, Angiolillo added, “I think we need to be cautious with making firm conclusions about dropping aspirin until data from ongoing trials such as GLOBAL LEADERS and TWILIGHT become available.”

Clopidogrel Resistance Related to Clinical Outcomes

The ADAPT-DES research group has previously examined the impact of high on-clopidogrel platelet reactivity (HCPR) at the time of DES implantation, finding that those with clopidogrel resistance had greater risks of adverse outcomes at 1 and 2 years.

The importance of HAPR, however, is less clear, as several smaller studies have provided conflicting results.

To help clarify the issue, Chung et al examined ADAPT-DES data on 8,526 all-comers patients who received dual antiplatelet therapy with aspirin and clopidogrel after undergoing successful PCI with DES. Platelet function was performed after the procedure using the VerifyNow assay (Accriva Diagnostics).

HAPR (≥ 550 aspirin reaction units) was found in 5.6% of patients, and HCPR (> 208 P2Y12 reaction units) was identified in 42.1%.

In a propensity-adjusted, multivariable analysis, HAPR was not associated with risks of various clinical outcomes.

Association Between High On-Aspirin Platelet Reactivity and Outcomes at 2 Years

Even in patients with concomitant HCPR, which was—as seen in prior studies—itself related to adverse outcomes, HAPR was not associated with worse ischemic outcomes or reduced bleeding.

Type of Platelet Function Assay Matters

The lack of a relationship between HAPR and clinical outcomes conflicts with the findings of the ISAR-ASPI registry, which showed that HAPR was associated with a greater risk of ischemic events at 1 year.

Chung et al say the discrepancy between the two data sets could be related to differences in patient population, the way platelet function was measured, and the cutoffs used to define HAPR. They note that different methods of platelet function testing have revealed varying rates of HAPR and its relationship with clinical outcomes.

The more sensitive the assay, the lower the rate of HAPR observed, Angiolillo noted.

The lack of standardization in how HAPR is measured and defined is a limitation of research in this field, Chung said.

“When you’re comparing different assays that are fundamentally measuring different aspects of platelet function they’re not going to be directly comparable,” she said. “There’s no standardization of the definition for high on-aspirin platelet reactivity and because of that a lot of studies have used different tests and then have defined cutoffs differently. So I don’t think studies that use different tests are necessarily directly comparable, but they can be used to give a general picture of what we think may be going on.”

Moving forward, Angiolillo said, “I think that there’s still a lot of research that needs to be done in the field of aspirin regarding whether its use is necessary when used in combination with more potent antithrombotic therapies, as well as understanding the best dosing regimen when used as monotherapy.”

Note: Several co-authors are faculty members of the Cardiovascular Research Foundation, the publisher of TCTMD.