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CYP2C19 Genotyping Safe, Feasible for Plavix Prescribing After Stent Procedure, Study Shows

American College of Cardiology's 2024 scientific meeting

ATLANTA – Genotyping to guide treatment with P2Y12 inhibitors is safe and feasible, researchers reported on Sunday at the American College of Cardiology's annual scientific meeting.

However, additional data are needed on the impact genotype-guided treatment management has on patients' clinical outcomes, they said.

In a proof-of-concept pilot study, researchers tested the ability of a pharmacogenomic program to inform antiplatelet prescribing decisions for about 100 patients at high risk for bleeding after a percutaneous coronary intervention (PCI) procedure.

"Post-discharge bleeding is very common" and can lead to death and spontaneous myocardial infarction, said Mandeep Singh, a cardiologist at Mayo Clinic and coauthor of the poster, during a session at ACC. "This is a very critical period."

All patients enrolled in the study initially received dual anti-platelet therapy (DAPT) comprising aspirin and Bristol Myers Squibb and Sanofi Aventis' P2Y12 inhibitor Plavix (clopidogrel). Although Plavix is a blood thinner widely prescribed by cardiologists, patients with certain variants in the CYP2C19 gene can't metabolize it. Still, physicians often choose to prescribe Plavix because other drugs in the same class are associated with a higher risk of bleeding.

Within the pilot, clinicians learned patients' CYP2C19 genotyping results on average within three days of giving them a blood test, so they could use the findings to inform the next steps in treatment.

After an average of five days on DAPT, based on the test results, patients could de-escalate treatment by discontinuing aspirin and continue on P2Y12 inhibitor monotherapy for 90 days. Roughly 30 percent of patients were determined to be intermediate CYP2C19 metabolizers and switched to an alternative P2Y12 inhibitor, typically Eli Lilly and Daiichi Sankyo's Effient (prasugrel), due to cost, Singh said. Patients with contraindications to Effient would receive AstraZeneca's Brilinta (ticagrelor).

About 70 percent of patients were determined to be normal, rapid, or ultrarapid metabolizers and continued with Plavix. No patients were poor metabolizers.

In 90 days of follow-up post-discharge, there was one possible stent thrombosis, and three patients — all of whom were on Plavix — had overt bleeding events that were related to transfusions. None of the patients died or had a stroke in the pilot study.

This suggests genotype-guided prescribing for P2Y12 inhibitor monotherapy after PCI is "safe and feasible" in patients who are at high bleeding risk, researchers wrote in the abstract.

"Larger randomized trials need to be performed to test the efficacy of this approach," Singh said, as well as to assess longer-term outcomes.

A separate poster presented Sunday detailed outcomes from a randomized study of 67 patients undergoing PCI, who required oral anticoagulation alongside DAPT and who would typically receive Plavix as part of standard care. However, according to Luis Ortega Paz, an assistant professor of medicine at the University of Florida College of Medicine-Jacksonville and coauthor of the poster, about half of the patients, 33, were determined likely to have impaired response to Plavix based on the ABCD‐GENE, a clinical and genetic risk score that stands for Age, Body Mass Index, Chronic Kidney Disease, Diabetes Mellitus, and Genotyping.

The score, developed at the University of Florida, incorporates the four clinical factors included in its name and factors in whether patients have CYP2C19 loss-of-function alleles to determine if they are likely to have an impaired response to Plavix due to high platelet reactivity and be at risk for thrombotic complications. Patients who were likely to have an impaired response to Plavix were randomized to receive either Plavix or Brilinta for 30 days, while the rest of the patients received Plavix and served as the control group.

Researchers found that patients who received Brilinta had significantly reduced platelet P2Y12 reactivity, as measured by P2Y12 reactive units in a blood-based assay, compared to the other groups, suggesting that patients with impaired Plavix response had better P2Y12 inhibitory effects with an alternative drug. After 30 days, in the randomized treatment arm, the lowest level of P2Y12 reactive units were significantly lower in patients treated with Brilinta than those who received Plavix. Peak levels of P2Y12 reactive units, defined as two hours after the patient received the medication, were also lower in Brilinta-treated patients than Plavix-treated patients in the randomized arm. Patients in the control arm had slightly higher P2Y12 reactive units than patients who received Plavix in the randomization arm, but significantly higher than those who received Brilinta.

Ortega Paz said he would like to see additional research on clinical outcomes. "This is a pharmacodynamic study," he stressed. "We cannot claim any findings on safety or efficacy."