SAN FRANCISCO -- Platelet function testing in patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI) may have little clinical utility in routine practice, researchers said.
At 3o days, the absolute and relative levels of platelet inhibition in response to adenosine diphosphate (ADP) P2Y12 receptor antagonists as assessed by the VerifyNow P2Y12 test were independent predictors of stent thrombosis, with a significant proportion of events independently attributable to clopidogrel hyporesponsiveness, Gregg W. Stone, MD, from Columbia University Medical Center in New York City, reported at a Transcatheter Cardiovascular Therapeutics (TCT) late-breaking clinical trials presentation.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Note that this large, prospective study indicates that the absolute and relative levels of platelet inhibition to ADP antagonists, but not the base level, are highly significant independent predictors of stent thrombosis within 30 days in a large patient population, but not in individual patients.
But the sensitivity and specificity of platelet function testing, "were only modest at best, which means there is tremendous overlap for any given patient with any given PRU [platelet reaction unit], making it difficult to predict on an individual level who would or would not develop stent thrombosis," Stone said.
For example, the median interquartile range for platelet responsiveness assessed by the P2Y12 test was 188 PRU (112 to 260) for patients without stent thrombosis and 252 PRU (206 to 311) for patients with stent thrombosis.
During TCT press conference, Stone said his institution has stopped using the VerifyNow test, but he said he still believed the test may have utility as a research tool.
Ajay J. Kirtane, MD, director of the interventional cardiology fellowship program at Columbia University Medical Center in New York City, who moderated the press conference, asked for a show of hands from cardiologists at the press conference to assess VerifyNow use and the response was unanimous: none were using it in clinical practice. But, like Stone, about half of the panel members said they used the test for research purposes.
Although prior studies have shown a correlation between platelet hyporesponsiveness to ADP antagonists and stent thrombosis, all lacked the power to provide definitive answers to a number of questions, including:
- What proportion of the risk of stent thrombosis at different times after stent implantation can be attributed to platelet ADP antagonist response, and how useful is this to reclassify the risk of stent thrombosis?
- What is the optimal cutoff for platelet reactivity to predict stent thrombosis?
- Is ADP antagonist hyporesponsiveness important in all patients (e.g., nondiabetics as well as diabetics; stable coronary artery disease versus acute coronary syndrome)?
To help answer these questions, Stone and colleagues conducted the ADAPT-DES study, a large-scale, prospective, multicenter registry that examined the relationship of platelet responsiveness and stent thrombosis after drug-eluting stent implantation.
They enrolled 8,575 patients who were at 11 sites between January 2008 and September 2010.
Platelet responsiveness to aspirin and clopidogrel (Plavix), as well as overall platelet responsiveness, was assessed with the VerifyNow Aspirin, P2Y12, and Glycoprotein IIb/IIIa inhibitor tests.
The 30-day rate of definite or probable stent thrombosis was low, occurring in 39 patients (0.46%), of which more than two-thirds were definite. Also, the vast majority of cases occurred within the first 12 days, Stone said.
Researchers found no relationship between aspirin resistance or the base P2Y12 unit and subsequent stent thrombosis, nor was there a relationship between the overall platelet responsiveness measured by the IIb/IIIa test and stent thrombosis.
"There was, however, a strong powerful relationship between the overall P2Y12 PRU level and subsequent stent thrombosis, and there was even a stronger relationship between the percent inhibition of clopidogrel-induced platelet aggravation and subsequent stent thrombosis," Stone said.
The two prespecified PRU cutoffs were >208 and ≥230. At the cutoff of 208, there was a greater response of each quintile of PRU, ranging from 0.18% to 0.79% for definite or probable stent thrombosis. A univariate analysis showed a hazard ratio of 3.89 (95% CI 1.90 to 7.98, P<0.001).
For the percentage of inhibition of clopidogrel-induced platelet aggravation of less than 11%, the stent thrombosis rate rose to 1.19%, 10 times greater than the lowest quintile. The univariate analysis showed a HR of 4.18 (95% CI 2.23 to 7.82, P<0.001) comparing the lowest quintile with the other four.
The predictive value of platelet testing for diabetics and nondiabetics was the same. However, there was a strong relationship between stent thrombosis and patients with acute coronary syndromes (ACS) (30 of the 39 patients with stent thrombosis had ACS).
For example, the rate of stent thrombosis was 0.22% among patients without ACS versus 0.68 among patients with ACS. "It was especially high in biomarker positive patients [0.42%] and even greater in patients with STEMI [1.60%]," Stone reported.
Stone concluded that the data can be positively applied to large patient populations, but are, "unlikely to provide useful information to guide clinical decision-making in most individual patients for the prevention of stent thrombosis at 30 days."
However, the degree of platelet responsiveness can be a useful predictor of 30-day stent thrombosis in patients with ACS compared versus those with stable disease, he said.
Disclosures
The ADAPT-DES trial is sponsored by the Cardiovascular Research Foundation with research support from Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi Sankyo, Eli Lilly, Volcano, and Accumetrics.
Stone reported consulting fees and honoraria from Abbott Vascular, Boston Scientific, Medtronic, Volcano, The Medicines Company, Daiichi Sankyo, and Eli Lilly.
Primary Source
Transcatheter Cardiovascular Therapeutics
Source Reference: Stone, G et al "ADAPT-DES: a large-scale, prospective, multicenter registry examining the relationship of platelet responsiveness and stent thrombosis after DES implantation" TCT 2011.