NEW YORK (Reuters Health) – A consensus statement compiled by an international panel proposes that the level of platelet reactivity during antiplatelet therapy is a better measure of thrombotic risk than is responsiveness to clopidogrel.
In the paper in the Journal of the American College of Cardiology for September 14, Dr. Paul A. Gurbel with Sinai Hospital of Baltimore, Maryland and colleagues note that high platelet reactivity to adenosine diphosphate (ADP) during treatment with clopidogrel has been seen.
“In 2003, my laboratory reported that clopidogrel was ineffective in up to approximately 30% of patients undergoing stenting. This meant that their platelets were not effectively inhibited and that they were potentially at increased risk for having thrombotic events,” Dr. Gurbel explained in emailed comments. “Our observations stimulated further work that demonstrated the key relation between highly reactive (i.e. uninhibited) platelets and thrombotic events in patients undergoing stenting.”
However, the consensus statement notes, routine measurement of platelet reactivity has not been widely adopted because methods of quantifying high on-treatment platelet reactivity have not been standardized, and there’s limited evidence that altering therapy based on platelet reactivity improves outcomes.
“This review provides a consensus opinion on the definition of high on-treatment platelet reactivity to ADP based on various methods reported in the literature and proposes how this measurement may be used in the future care of patients,” the authors write.
They note that baseline ADP-induced platelet aggregation varies between individuals, and so measuring clopidogrel inhibition of platelet activity may overestimate or underestimated ischemic risk depending on pre-treatment platelet responsiveness. Therefore, the absolute level of platelet reactivity during treatment (i.e., on-treatment platelet reactivity) is a better way to stratify patient risk for ischemic/thrombotic events following PCI.
The panel identifies four methods of defining high on-treatment platelet reactivity associated with thrombotic risk:
1) Platelet reactivity index (PRI) >50% by VASP-P analysis (phosphorylation state of vasodilator-stimulated phosphoprotein);
2) >235 to 240 P2Y12 reaction units by VerifyNow P2Y12 assay (Accumetrics, San Diego, California);
3) >46% maximal 5-micromol/L ADP-induced aggregation;
4) >468 arbitrary aggregation units/min in response to ADP by Multiplate analyzer (Dynabyte Informationssysteme, Munich, Germany).
The authors recommend that platelet function testing be considered for determining antiplatelet therapy for patients with prior stent thrombosis and those undergoing high-risk PCI. “However, it should not be performed routinely in the absence of prospective trials to prove that alteration of therapy based on testing actually improves outcomes and is safe,” Dr. Gurbel advised.
He added, “One of the most important things we are learning is that risk accrues significantly after a cutpoint of platelet reactivity is reached. Thus, we may avoid bleeding in the future by achieving platelet reactivity in the patient just below the cutpoint and thus not drive it unnecessarily too low in order to avoid bleeding.”
J Am Coll Cardiol 2010;56:919-933.
