ADAPT-DES Registry Examines Platelet Responsiveness as Predictor of DES Thrombosis

 

November 15, 2011

November 15, 2011 — Results of ADAPT-DES (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) were presented at the 23rd annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. The registry examined the relationship of platelet responsiveness to antiplatelet medications; the correlation of poor response; and overall platelet aggregation while on dual antiplatelet therapy to the risk of drug-eluting stent (DES) thrombosis after 30 days. It is the largest such registry to date to fully examine these relationships.

Prior studies have emphasized the absolute level of platelet activation/aggregation to antiplatelet medication. The role of the baseline level of platelet activation and the percentage of platelet inhibition in response to these therapies have, however, largely been unstudied prior to ADAPT-DES.

In addition, the impact of poor platelet response to aspirin, and overall platelet aggregation while on dual antiplatelet therapy (DAPT) on the risk of stent thrombosis has not been fully examined.

In the registry, 8,575 patients undergoing percutaneous coronary intervention (PCI) with DES were enrolled at 11 sites between January 2008 and September 2010. The researchers assessed platelet reactivity to aspirin and clopidogrel as well as overall platelet responsiveness with the VerifyNow Aspirin, P2Y12, and IIb//IIIa tests after successful implantation of drug-eluting stents. Definite or probable stent thrombosis occurred in 39 patients (0.46 percent) after 30 days.

The researchers found that absolute and relative levels of platelet inhibition in response to ADP antagonists as assessed by the VerifyNow P2Y12 test are powerful independent predictors of stent thrombosis within 30 days; a significant proportion of events were independently attributable to clopidogrel hyporesponsivenes.

In contrast, the baseline level of platelet P2Y12 response, as well as aspirin and overall platelet responsiveness after DAPT loading as assessed by VerifyNow, were not shown to be related to the 30-day rate of stent thrombosis.

“These results suggest that agents which more effectively inhibit ADP-induced platelet activation should reduce 30-day stent thrombosis when applied to large patient populations,” said lead investigator, Gregg W. Stone, M.D. Stone is director of cardiovascular research and education at New York-Presbyterian Hospital/Columbia University Medical Center. He is also professor of medicine, division of cardiology at Columbia University College of Physicians and Surgeons. Stone also serves as co-director, medical research & education division at the Cardiovascular Research Foundation.

“However, the modest sensitivity and specificity of platelet function testing, coupled with the low prevalence of events, implies that testing of platelet ADP antagonist responsiveness is unlikely to provide useful information to guide clinical decision-making in most individual patients for the prevention of stent thrombosis at 30 days,” said Stone.“The degree of platelet responsiveness to antiplatelet loading is useful to predict 30-day stent thrombosis in diabetic and non-diabetic patients, as well as those with ACS, but may have less clinical utility in patients with stable coronary artery disease (CAD),” Stone said.

“There was a low stent thrombosis rate in patients with stable CAD, which, coupled with the poor prognostic utility of platelet function testing in this setting, suggests that assessing DAPT response in patients without ACS undergoing PCI is unlikely to provide incremental clinical utility. The relationship between platelet responsiveness testing and the occurrence of late and very late stent thrombosis, in patients who have maintained and discontinued DAPT, will be assessed during the two-year clinical follow-up phase of the ADAPT-DES study.”

The ADAPT-DES trial is sponsored by the Cardiovascular Research Foundation; Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi Sankyo, Eli Lilly, Volcano, and Accumetrics provided research support. Stone reported consulting fees and honoraria from Abbott Vascular, Boston Scientific, Medtronic, Volcano, The Medicines Company, Daiichi Sankyo and Eli Lilly.

For more information: www.crf.org