While pharmacogenomic information does influence antiplatelet prescribing patterns—especially for patients with loss of function alleles—clinicians appear to also rely heavily on clinical factors, according to new randomized data.

With evidence lacking that genetic testing influences outcomes, it’s appropriate today for clinicians to “incorporate the genetic testing with your clinical gestalt,” senior author Jay Giri, MD (Hospital of the University of Pennsylvania, Philadelphia), told TCTMD after the presentation of the ADAPT study yesterday at the American College of Cardiology 2018 Scientific Session. “The clinical practice of precision medicine is going to be about more than just precise genetics,” he said.

Giri and colleagues, including Sony Tuteja, PharmD, MS (Perelman School of Medicine at the University of Pennsylvania, Philadelphia), who presented the findings here, randomized 504 patients undergoing PCI and stenting to CYP2C19 genotyping in the cath lab or to usual care. Genotyping was used to identify patients who carried clopidogrel loss-of-function alleles. The ultimate choice of antiplatelet agent remained at the discretion of the treating interventional cardiologist, however, and patients were preloaded with an antiplatelet agent before the genetic information was available (average turnaround time was 1.4 hours).

Overall, prasugrel (Effient; Eli Lilly) or ticagrelor (Brilinta; AstraZeneca) were used more often in patients who underwent genotyping than in the standard care arm (30% vs 21%; P=0.03). Specifically, the more potent agents were used more often in loss-of-function allele carriers who were genotyped than in “normal” clopidogrel responders (53% vs 22%; P<0.001).

Interestingly, the rate of agreement between clinicians and what the genetic information recommended was 71%. Reasons for nonagreement among patients who were intermediate or poor clopidogrel metabolizers typically related to presence of stable CAD, cost, contraindications, and physician preference. In patients who were considered normal or rapid metabolizers, the disagreement typically arose because of disease characteristics, the patient already being on the therapy, ACS diagnosis, or recurrent events.

Patients who were on clopidogrel before hospital admission were two times more likely to stay on the drug regardless of genotype (OR 2.04; 95% CI 1.22-3.45). However, patients who were on ticagrelor or prasugrel prior to genotyping were 99 times more likely to stick with them (OR 99.3; 95% CI 13.2-744).

Post hoc analysis showed no difference in clinical outcomes, although the study was not powered to determine this, both Giri and Tuteja acknowledged.

What really guides prescribing habits?

“There’s more to making these decisions than just the genetics,” Tuteja said in a discussion following her presentation. “The genetics only explain 12% of the platelet aggregation results for clopidogrel nonresponse, so I think there’s a lot of other factors that go into deciding whether a patient will have an adverse event after a stent. That’s why we gave the physicians the choice whether to switch or not.”

With societal guidelines recommending prasugrel and ticagrelor in patients with ACS, this trial will only add to the “controversy,” she adds. “We need more studies to show what to do in those normal metabolizers, especially in the context of ACS.”

Likewise, Giri added, when physicians in this study saw complex disease yet were told by the genetic information the patient was a good responder to clopidogrel, “they still went ahead in many cases . . . to use prasugrel or ticagrelor because it made them feel better.” Whether this makes the patient feel better, though, remains uncertain, he said.

Tuteja explained that they designed the trial in a randomized fashion because of the skepticism that surrounded pharmacogenomic testing when they began. “We didn’t want to just produce a study that said, 'Yep, the physicians followed the recommendations and all is good.' We wanted to do it in a very thoughtful manner that might provide some insight on what goes into antiplatelet prescribing behaviors,” she told TCTMD.

Panelist Kristin Patton, MD (University of Washington Medical Center, Seattle), commented that the ADAPT findings raise the “question of whether the doctors were continuing to prescribe out of habit vs because of real clinical decision-making. I think that would be an interesting area to look at in the future.”

The study was conducted at two hospitals, which allowed researchers to identify differences in agreement patterns between the two, Tuteja observed. “A lot of education” needs to accompany the continued expansion of genotyping across institutions, she suggested. Examples of that could be “live education or clinical decision support tools that come up in electronic health records to alert physicians not to prescribe certain drugs based on genotype,” she suggested.