Patients undergoing PCI and being treated with clopidogrel should be routinely tested for platelet function because patients have individualized responses to the drug, Jurriën M. ten Berg, PhD, said during a presentation at the 22nd annual Transcatheter Cardiovascular Therapeutics (TCT) meeting Sept. 23 in Washington, D.C.
The fact that there are poor metabolizers of clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) has recently been brought to the forefront. In March, the FDA placed a black box warning on clopidogrel after learning that 2 to 14 percent of the population is at risk of being poor responders to the antiplatelet drug due to the CYP2C19 loss-of-function allele.
“The first question is why should we measure platelet function in the first place and there are three good reasons,” ten Berg said.
First, patients have an individual variability that is based on platelet response, he said. A previous study done by researchers in Amsterdam showed that MI patients who have spontaneous platelet aggression do significantly worse on clopidogrel than patients with normal platelet function.
Secondly, patients have marked individual responses to antiplatelet drugs, particularly clopidogrel, and testing for patient function can decipher normal, as well as poor responders.
Lastly, ten Berg offered, “A one-size-fits-all regimen, which is dictated by the current guidelines, doesn’t work in all patients." Therefore, measuring platelet function can find the optimal treatment for non-responders and for those who have recurrent thrombotic events, which occurs in over 10 percent of patients.
“Many studies have shown an association between high platelet reactivity and clinical outcomes,” said ten Berg. These studies have drawbacks due to their small sample sizes and use of upper quartile platelet reactivity, rather than use of cutoff values that are based on receiver-operator characteristic curve analysis. Additionally, he said that most studies overlook the comparison of different platelet tests.
Ten Berg and colleagues at the St. Antonius Hospital in Nieuwegein, the Netherlands, during the POPULAR trial performed a head-to-head comparison of platelet function tests and found four that significantly predicted adverse outcomes—light transmittance aggregometry (LTA)-5 and 20, VerifyNow P2Y12 assay (Accumetrics) and Plateletworks (Helena Laboratories).
“Patients with high platelet reactivity do significantly worse than the ones who have normal platelet reactivity and that holds true for the four tests evaluated,” ten Berg and colleagues said. They found that high platelet reactivity was associated with a 12.1 percent incidence rate of CV events compared to a rate of 6 percent in patients without high platelet reactivity.
Ten Berg said that patients with high platelet reactivity, despite use of clopidogrel, have a higher risk of periprocedural MI, and using these platelet function tests in routine practice can help alleviate this risk. Additionally, he said that studies have shown that measuring platelet functions and adding a glycoprotein IIb/IIIa inhibitor to aspirin and clopidogrel treatment can reduce the risk of MI in the short term. Additionally, previous studies have shown that administering higher loading doses of clopidogrel to patients who are unable to metabolize the drug can help improve outcomes.
He noted that 75 percent of patients who undergo PCI have normal platelet reactivity and respond very well to clopidogrel on long-term follow-up.