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Genetic test for clopidogrel response after PCI helps influence antiplatelet decisions
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ORLANDO, Fla. — Performing a genetic test for nonresponse to clopidogrel often influenced physician choice of antiplatelet prescription after PCI, according to new data from the ADAPT trial.
Clinical considerations also played a factor, Sony Tuteja, PharmD, MS, research assistant professor of translational medicine and human genetics at Penn Medicine, said during a presentation at the American College of Cardiology Scientific Session.
Patients with certain loss-of-function alleles often do not respond to clopidogrel and may be candidates for prasugrel (Effient, Daiichi Sankyo/Eli Lilly) or ticagrelor (Brilinta, AstraZeneca)
Tuteja and colleagues conducted the ADAPT pragmatic randomized clinical trial in which 504 patients (mean age, 63 years; 74% men) were randomly assigned to genotyping or the usual care after PCI with stenting to help determine which antiplatelet therapy they should receive.
“We wanted to do this testing in a thoughtful manner in which we were providing evidence about how physicians were reacting to genetic data in the context of antiplatelet prescribing,” Tuteja told Cardiology Today’s Intervention. “We weren’t powered for outcome differences, but we wanted to get some insight on what factors go into antiplatelet prescribing.”
The primary endpoint was proportion of patients receiving prasugrel or ticagrelor. Secondary endpoints included agreement with genotype-guided antiplatelet recommendations, MACE and major bleeding.
Patients assigned genotyping underwent a test to determine whether they were a carrier of the CYP2C19*2 or CYP2C19*3 allele; if so, the treating physician was informed that the patient was recommended for treatment with prasugrel or ticagrelor. If the patient was not a carrier, the physician was informed that the patient was recommended for treatment with clopidogrel. Treating physicians were not required to follow the recommendations.
Since drug-gene outcomes data are not available, “we decided to allow physicians to make their decisions with gene information as one piece of information in the context of overall clinical presentation, similar to how they would deal with other laboratory testing,” Jay S. Giri, MD, MPH, director of peripheral intervention and assistant professor of medicine at the Hospital of the University of Pennsylvania and a Cardiology Today Next Gen Innovator, said in an interview.
For patients in the usual-care group, a swab was taken for analysis after the study.
In the genotyped group, 28% of patients had at least one loss-of-function allele, Tuteja said.
The genotyped group was more often prescribed prasugrel or ticagrelor than the usual-care group (30% vs. 21%; P = .03), she said.
Prasugrel or ticagrelor use was also greater in patients who had at least one loss-of-function allele. Within the genotyped group, those with at least one loss-of-function allele received prasugrel or ticagrelor 53% of the time, compared with 22% of those without such an allele (P < .001). Those in the genotyped group with loss of function also were prescribed prasugrel or ticagrelor more often than those in the usual-care group (53% vs. 21%; P < .001), Tuteja said.
The rate of agreement with genotype-guided recommendations was 71%, according to the researchers.
“I think it’s important that physicians are not blindly following the genotype results,” Tuteja told Cardiology Today’s Intervention. “They look at the whole picture of the patient when deciding which antiplatelet therapy is best for them, including application of the procedure, what other drugs they are taking and perhaps other clinical factors that would put them at higher risk for bleeding complications.”
A major predictor of antiplatelet decision was prior use of that antiplatelet. Patients who previously took clopidogrel were more likely to remain on clopidogrel (OR = 2.04; 95% CI, 1.22-3.45) and those who previously took prasugrel or ticagrelor were 99 times more likely to remain on their therapy (OR = 99.3; 95% CI, 13.2-744).
However, Tuteja said, genotyping did not influence prescribing decisions for patients already on prasugrel or ticagrelor, as the rate of agreement with genotype-guided recommendations was only 21% for those patients, compared with 76% for those already on clopidogrel and 73% for those not previously taking an antiplatelet (P < .0001).
“Once a patient is already on more potent agents, the thought to downgrade them to clopidogrel is very hard to overcome,” she said.
Giri noted that the reluctance to switch could be due to “many of these patients having declared themselves as not having complications on prasugrel and ticagrelor. The physicians have got some insight into these patients’ unique bleeding risk. There is some rationale apart from inertia.”
There was no difference between the groups in MACE or major bleeding. – by Erik Swain
Reference:
Tuteja S, et al. Featured Clinical Research I. Presented at: American College of Cardiology Scientific Session; March 10-12, 2018; Orlando, Fla.
Disclosures: Giri and Tuteja report no relevant financial disclosures.