Platelet-Function Testing Might Benefit Select PCI Patients, Says Expert Panel

October 08, 2013

MUNICH, GERMANY — A new position paper on the current role of platelet-function testing in patients undergoing PCI highlights the current state of evidence and advocates a selective role for testing in some patients, such as those at high risk for stent thrombosis[1]. The experts, from the Working Group on Thrombosis of the European Society of Cardiology (ESC), stress that clinical presentation and patient characteristics should guide antiplatelet therapy during and after PCI.

For selected patients, those who are suspected of having an increased risk for thrombotic or bleeding events based on clinical and/or procedural characteristics, "platelet-function testing may help the decision-making by providing information on the level of platelet reactivity," according to Dr Dániel Aradi (Heart Center, Balatonfürd, Hungary) and colleagues in their report, published online September 25, 2013 in the European Heart Journal.

In Europe, the ESC guidelines on non-ST-segment-elevation ACS state that platelet-function testing is a class IIb indication. Testing platelet reactivity can be performed when clopidogrel is used, although prasugrel (Effient, Lilly/Daiichi-Sanyo) and ticagrelor (Brilinta, AstraZeneca) are recommended for ACS patients and those with ST-segment-elevation MI. Clopidogrel, however, still has a class I indication in ACS in Europe because not all countries have access to the newer agents.

Dr Dirk Sibbing (Ludwig Maximilians University, Munich, Germany), one of the coauthors of the report, told heartwire that platelet-function testing is not recommended for all PCI-treated patients because the randomized, controlled clinical trials to date have not supported the concept of routine testing. That said, he noted there are large differences in the level of platelet inhibition during treatment with clopidogrel and that high platelet reactivity is associated with an increased risk of stent thrombosis.

"We shouldn't lose sight of the fact that antiplatelet drugs are the most important drugs for the patient," said Sibbing. "It is important for the physician and patient to know if the response to the drug is fine."

The Available Assays

Based on current evidence, the ESC working group recommends three assays for monitoring P2Y12 inhibition: the VerifyNow P2Y12 assay (Accumetrics), the Multiplate device (Diapharma) with the adenosine diphosphate (ADP) kit, and the vasodilator-stimulated phosphoprotein (VASP) assay.

In addition, the position paper highlights the importance of standardized cutoff values with the assays to give physicians an estimation of thrombotic and bleeding risks. In addition, the experts discuss the clinical relevance of the "therapeutic window," the period in which thrombotic and bleeding risks might be lowest.

"The reason for coming out with this is to provide a paper that summarizes the data with the assays that are there and can be used for platelet-function testing and also to highlight the fact that the best way to use these assays is to use standardized assays," said Sibbing. "The whole field of platelet-function testing is a difficult field. It's not easy to test platelets the right way. It's much more difficult than testing serum creatinine, say, or other values. Standardized assays are of utmost importance so that we are able to compare results."

In addition to providing guidance on monitoring, the experts discuss the prognostic value of platelet-reactivity testing. They note that high on-treatment platelet reactivity to ADP is an independent predictor of thrombotic events, especially early stent thrombosis in patients treated with clopidogrel after PCI. The prognostic value of high on-treatment platelet reactivity is less established in patients with stable angina.

Sibbing said that studies will be needed to determine the predictive capability of various cutoff values for the estimation of risk. He said that determining treatment based on platelet-function results is the most difficult aspect of the field, and the routine testing of all patients for this purpose will require further studies, something that is ongoing. He suspects that platelet-function testing might be particularly beneficial in the ACS setting given the high risk for recurrent events.

Personalization of Antiplatelet Therapy

In late August, the US Food and Drug Administration (FDA) granted 510(k) clearance to the Spartan RX assay and genotyping platform to identify individuals with variations in the CYP2C19 gene. The assay and genetic-testing system requires an in-office swab, and results are available in an hour. The assay and testing system is indicated for use as an aid to clinicians in determining treatment options for drugs metabolized by the CYP2C19 gene, specifically drugs affected by the *2, *3, and *17 alleles.

Currently, the Mayo Clinic is using the Spartan Rx system in the 6000-patient TAILOR-PCI trial. TAILOR-PCI is a study that is testing tailored antiplatelet treatment based on clopidogrel response in patients undergoing PCI.

In addition to that trial, the TROPICAL-ACS study has also just started. The study, a multicenter effort involving 2600 patients, will assess the benefit of a tailored antiplatelet therapy in ACS patients undergoing PCI. In TROPICAL-ACS, the personalization of antiplatelet therapy will be guided by platelet-function testing using the Multiplate device.

Identifying Nonresponders

Based on testing performed at their research center, Sibbing told heartwire that  he suspects the high end of clopidogrel nonresponders is in the range of 10% to 20%. The large majority of patients show an adequate response to the antiplatelet drug, and this is the reason there is such a low rate of stent thrombosis in numerous studies. In these trials, the rate of stent thrombosis is just 0.5% in the first 30 days, said Sibbing.

"Platelet-function testing would be a way for us to identify patients who don't respond," he said. "The next step then will be to know whether treatment should be changed. For this decision, [platelet-function] testing should be used as just one marker, among many others, to make the decision. You also have to look at the age of the patient, the other drugs they might be taking, and what comorbidities they might have. It's difficult."

The expert group states that platelet-function testing should be considered if the results might change the antiplatelet treatment strategy, such as in patients with an unexpected definite stent thrombosis despite adherence to clopidogrel or those with an elevated risk for stent thrombosis. The treatment decision should be based on the patient's thrombotic risk and bleeding risk, said Sibbing.

Whether platelet-function testing can help reduce the risk of adverse thrombotic events, Sibbing said, remains unproven, although it has not yet been disproven. "I think there is room for testing and testing will be important," he said Sibbing. "I think this is built on the fact that we now have alternative drugs available—specifically with clopidogrel, prasugrel and ticagrelor. So testing will play a role."

Sibbing reports research grants/consulting fees from Daiichi Sankyo and Verum Diagnostica and lecture fees from Roche, CSL Behring, and Eli Lilly. Disclosures for the coauthors are listed in the paper.

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