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March 28, 2020

TAILOR-PCI Trial Evaluates Genetic Testing to Guide Post-PCI Antiplatelet Therapy

March 28, 2020—The American College of Cardiology (ACC) announced that findings from the TAILOR-PCI international clinical trial to test the effectiveness of genetic testing to guide which antiplatelet medication was given to patients after percutaneous coronary intervention (PCI)—were presented by coprincipal investigator Naveen L. Pereira, MD, at the ACC's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC), which is being held this year as a virtual conference.

The study was funded by the Mayo Clinic in Rochester, Minnesota, in collaboration with the National Heart, Lung, and Blood Institute. Spartan Bioscience, Inc, supplied the genetic tests used. Dr. Pereira is Professor of Medicine at Mayo Clinic. The National Heart, Lung, and Blood Institute has also funded an extended follow-up study to evaluate the effect of genotype guidance beyond the 12-month follow-up period of TAILOR PCI. 

According to ACC, the TAILOR-PCI trial did not meet its endpoint of a 50% reduction at 1 year in the combined rate of death, heart attack, stroke, stent thrombosis, or a recurrent heart attack-like presentation.

However, the investigators observed a 34% drop in these events in the year after PCI. The trial also revealed a statistically significant 40% reduction in the total number of events per patient receiving genetically guided treatment compared with patients who received standard treatment. 

In the ACC press release, Dr. Pereira commented, “Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy, with approximately one-third fewer adverse events in the patients who received genetically guided treatment compared with those who did not.”

Dr. Pereira added that a post hoc analysis, performed after the investigators knew the study’s results, found an approximate 80% reduction in the rate of adverse events in the first 3 months of treatment among patients who received genetically guided therapy compared with those who did not. This period immediately after PCI is when patients are at the highest risk for adverse events, he noted.

Furthermore, Dr. Pereira stated, “We now know from clinical practice and other studies that antiplatelet drug therapy is critical during the first 3 months after PCI. This finding suggests that the lion’s share of the benefit of genetically guided therapy may occur during this high-risk period. Because this wasn’t a preplanned analysis, we can’t draw firm conclusions from it, but it merits further study.”

Dr. Pereira explained that in the United States, approximately 30% of people carry the genetic variant that makes them less capable of metabolizing and, hence, activating clopidogrel. The proportion increases to 50% among people of Asian heritage.

He said that a simple-to-perform genetic test can identify whether a patient carries the abnormality. However, no prospective clinical trials have shown that outcomes are better for patients who have the abnormality when the test is used to guide their treatment. For this reason, guidelines published by the ACC and the American Heart Association do not currently recommend that patients be tested for the abnormality before being prescribed clopidogrel. The TAILOR-PCI trial was designed to fill this knowledge gap.

As summarized in the ACC press release, the trial enrolled 5,302 patients who had been treated for an arterial blockage with one or more stents. The median age of patients was 62 years, and 75% were men. 

Patients were randomly assigned either to a group that was tested for the genetic variant affecting clopidogrel metabolism or to a group that received standard treatment without genetic testing. In the first group, 35% of patients were found to have the genetic variant and were prescribed another antiplatelet medication, ticagrelor, while those without it got clopidogrel. In the second group, all patients were prescribed clopidogrel. The patients were enrolled at 40 medical centers in the United States, Canada, Mexico, and South Korea, and followed for 1 year. 

Among patients who carried the genetic variant, the primary endpoint occurred in 35 (4%) in the group that received genetically guided treatment, compared with 54 (5.9%) in the conventionally treated group at 1 year. 

The reduction in the number of adverse events per patient also has important clinical implications, Dr. Pereira said, adding, “Multiple adverse events represent a higher burden on the patient, so it is encouraging to see a significant reduction in cumulative events with genetically guided therapy.” 

Among patients with the genetic variant, there were no differences in the safety endpoint of TIMI major bleeding (fatal bleeding, bleeding in the brain, or any bleeding that requires medical assessment or treatment) or minor bleeding between those receiving genetically guided treatment (16 patients, 1.9%) and those in the conventional treatment arm (14 patients, 1.6%) at 1 year. 

In the ACC announcement, Dr. Pereira explained that recent improvements in the standard of care after PCI may have contributed to the trial not achieving its primary endpoint. 

When the TAILOR-PCI trial was designed in 2012, approximately 10% to 12% of patients who received a stent could be expected to have a major adverse event within a year. Over the course of the trial, the standard of care evolved through greater use of drug-coated stents and other treatments, which reduced the expected rate of adverse events in a year to about 5%. This change in technology substantially improved care for patients, but at the same time may have made it more difficult for the trial to reach its goal of a 50% reduction in adverse events with the number of patients enrolled, Dr. Pereira said. 

Dr. Pereira noted that no special expertise in laboratory testing is required to perform the genetic test. In the trial, the tests were done by study coordinators who did not have a background in laboratory medicine and who were able to perform the tests in a consistent, reproducible fashion after receiving brief training.

The next step will be to analyze the cost effectiveness of genetically guided therapy, stated Dr. Pereira in the ACC announcement.

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