Expert Discusses Potential Role for Platelet Function, Genetic Testing
No prospective trials have demonstrated improved outcomes associated with individually tailored therapy based on the results of platelet function or genetic testing, but some study data still indicate the tests are useful in certain settings, said Paul A. Gurbel, MD, of the Sinai Center for Thrombosis Research, Baltimore, Md., in a lecture at TCT 2014.
According to Gurbel, platelet function testing may be appropriate in several scenarios, such as in high-risk PCI treated with clopidogrel in patients who are at increased risk of stent thrombosis or are vulnerable to catastrophe if such events occur. It also is helpful in determining when clopidogrel-treated patients can safely undergo surgery. Genetic testing, he added, should be considered in P2Y12 inhibitor-naive patients.
Lack of adequate trial data
Without positive prospective trial data, researchers question whether measuring platelet function testing to personalize therapy is warranted, Gurbel said.
Three major prospective trials of personalized antiplatelet therapy — GRAVITAS, TRIGGER-PCI and ARCTIC — showed no benefit to testing. “All of these trials are inadequate to refute the utility of personalization,” he countered. “These are not the final word on whether or not to personalize. These trials were neutral, and that’s unarguable. But they do have limitations.”
The limitations include that all patients were low risk, and therefore events were few and the studies undersized, Gurbel commented. In addition, there were low post-discharge event rates in all the trials and non-uniform protocols in the ARCTIC trial.
“The challenge for future randomized trials is that the event rates are low,” Gurbel said. “We need to sort out the patients who are at higher risk who will stand the greatest chance of [deriving benefit from] personalizing antiplatelet therapy.”
Potential for platelet testing
Gurbel pointed to a study published this year by Aradi et al in the Journal of the American College of Cardiology indicating that platelet function testing may be appropriate in high-risk ACS patients after successful PCI.
In the study, all patients underwent testing, with antiplatelet therapy altered according to its results. Patients with high platelet reactivity who received prasugrel (Effient, Daiichi Sankyo/Eli Lilly) demonstrated a 1-year risk of combined all-cause mortality, stent thrombosis, MI or stroke comparable to that of patients without high platelet reactivity who received clopidogrel (HR 0.90; 95% CI 0.44-1.81; P=.76). On the other hand, patients with high platelet reactivity who received clopidogrel at doses adjusted to reflect testing results had unfavorable outcomes (HR 2.27; 95% CI 1.45-3.55; P<.0001).
The ongoing TROPICAL-ACS study should provide further data on platelet testing in high-risk patients, Gurbel said. In addition, findings from the TARGET-CABG study, which he and fellow researchers published in 2012 in Circulation: Cardiovascular Interventions, suggest that preoperative platelet function testing may help surgeons determine when it is safe for clopidogrel-treated patients to undergo CABG.
Awaiting answers about genotyping
According to Gurbel, data from meta-analyses have indicated that carriers of the CYP2C19 loss-of-function allele tend to have higher risk of stent thrombosis. Yet genotype is an “imperfect indicator of phenotype,” he stressed, citing his research showing that some carriers can have low on-treatment platelet reactivity with clopidogrel.
Researchers thus await the outcomes of the TAILOR-PCI trial, which is individualizing therapy for ACS patients according to CYP2C19 genotype, to clarify the role of genetic testing for personalized treatment, he said.
- Gurbel reports receiving research grant support from AstraZeneca, CSL, Daiichi Sankyo/Eli Lilly and Company, Haemonetics, HCRI and the NIH as well as consultant fees/honoraria from AstraZeneca, Boehringer Ingelheim, CSL, Daiichi Sankyo/Eli Lilly and Merck. He has patents in the field of platelet function testing.