ADAPT-DES: Risk of Early Stent Thrombosis in DES Predicted by Platelet Inhibition

SAN FRANCISCO, CALIF.—Early stent thrombosis in patients implanted with DES can be effectively predicted by absolute and relative levels of platelet inhibition, and the risk of late stent thrombosis increases with time, according to two late-breaking trial presentations at TCT 2011.

The large-scale, prospective, multi-center registry study ADAPT-DES led by TCT Course Director Gregg W. Stone, MD, of Columbia University Medical Center, New York, included 8,575 patients presenting with stable CAD (48.3%) or ACS (51.7%) treated with DES between 2008 and 2010. Patients were given DAPT and tested for platelet response using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA).

Definite or probable stent thrombosis occurred in 39 (0.46%) patients. Prespecified measures PRU=208, PRU≥230; and P2Y12 inhibition ≤ 11%, were significantly associated with subsequent stent thrombosis after multivariate analysis (see Figure). Sensitivity and specificity thresholds for PRU and aspirin ranged from 57% to 94%.

“The modest sensitivity and specificity of platelet function testing, coupled with the low prevalence of stent thrombosis, 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,” Stone said.

He concluded that the 30-day findings of this study confirm that the levels of platelet inhibition in response to ADP antagonists are “powerful independent predictors of stent thrombosis with a significant proportion of events independently attributable to clopidogrel hyporesponsiveness. In contrast, the base 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 data suggest that agents which more effectively inhibit ADP-induced platelet activation should reduce 30-day stent thrombosis when applied to large patient populations,” Stone added. “The degree of platelet responsiveness to ADP antagonist 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 CAD.”

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 2-year clinical follow-up phase of the ADAPT-DES study.

Stent thrombosis risk increases with time

Ron Waksman, MD, of the Cardiovascular Research Institute, Washington D.C., presented data on DESERT, the largest case-control registry of late and very late stent thrombosis patients treated with DES. To determine the correlates of late stent thrombosis (longer than 30 days post-stent implantation), researchers studied data from 956 patients with (n=478) or without (n=478) stent thrombosis. Follow-up for stent thrombosis patients was conducted at 30 days, 6 months, an 1, 2 and 3 years.

Thirty-five percent of stent thrombosis events in the study arm occurred more than 4 years after stent implantation. Of these patients, 67% presented with STEMI and 22% with NSTEMI or ACS. At the time of stent thrombosis, 29.8% of the patients were on DAPT, and of those not taking DAPT (64.9%), 43.9% stopped therapy within 5 days of the stent thrombosis event.

At 1-year follow-up the mortality rate was 1.67% and the MACE rate was 16.54% in patients who were discharged alive after treatment for their stent thrombosis.

After noting that 90% of all patients had first-generation DES, Waksman said, “Patients who had first-generation DES continue to be at risk for late stent thrombosis even beyond 7 years. Younger patients, smokers, black race, patients with multivessel disease, STEMI or SVG lesions are at higher risk of developing late stent thrombosis and should be reconsidered for DES or for a potent or longer DAPT regimen.”

Panelist Matthew J. Price, MD, of the Scripps Clinic, La Jolla, Calif., noted a selection bias in the study because patients “got to the laboratory. The mechanisms of the related stent thromboses are unknown, whether it’s late stenosis with a clot or a plaque rupture within the stent. This could perhaps lead to different clinical presentations. So it’s important to understand the mechanisms of these late events.”

Study details

About a third of the ADAPT-DES patients had diabetes with 11.6% of them treated with insulin. The average age of these patients was 64 years and about three quarters were male.

Patients in the stent thrombosis group of DESERT were typically younger (P<.001); black (P=.044); current smokers (P<.001); and had either prior PCI (P=.002) or MI (P=.003).