ACC.2020/WCC. The TAILOR-PCI trial found benefit to genotype-guided therapy in first 3 months post-PCI, although 1-year results fell short.
The TAILOR-PCI trial, which used genetic testing to guide post-PCI antiplatlet therapy, did not meet the primary goal of reducing by 50% the incidence of serious adverse cardiovascular (CV) events (eg, stroke, MI) during the year after the procedure, according to a press release from the American College of Cardiology (ACC).
Trial authors did report, however a 34% reduction in these events at the 1-year mark and also a significant reduction in the number of events experienced per patient. Results were presented at the American College of Cardiology’s Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).
The study's primary endpoint was to reduce by half at one year the combined rate of death, heart attack, stroke, stent thrombosis or recurrent MI. While falling short of that outcome, the authors report a statistically significant 40% reduction in the total number of events per patient receiving genetically guided treatment vs patients who received standard treatment.
TAILOR-PCI is the largest cardiology trial to date to test the effectiveness of using genetic testing to guide treatment choice.
“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,” said Naveen L. Pereira, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and co-principal investigator of the study, in an ACC press release.
Pereira added that a post hoc analysis found a nearly 80% reduction in the rate of adverse events in the first 3 months of treatment in the genetically-guided therapy group vs those receiving standard care.
“We now know from clinical practice and other studies that antiplatelet drug therapy is critical during the first three months after PCI,” he said in the press release. “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 pre-planned analysis, we can’t draw firm conclusions from it, but it merits further study.”
Dual antiplatelet therapy post PCI with clopidogrel and aspirin is the gold standard. However, a genetic variant in the CYP2C19 enzyme system blocks clopidogrel metabolism, reducing the drugs’ efficacy and increasing risk for morbidity and mortality.
To date there have been no prospective clinical trials to study whether outcomes are improved for carriers of the abnormality when the simple-to-perform genetic test is used to guide treatment. In fact, absent this evidence, current ACC AHA guidelines do not recommend such testing.
The trial enrolled 5,302 post-PCI patients. Median age was 62 years, 75% were men. Randomization was to a group that was tested for the CYP2C19 genetic variant or to one that received standard treatment without testing.
Of patients in the tested group, 35% were found to have the genetic variant and were prescribed ticagrelor; those without it got clopidogrel. In the non-tested group, all received clopidogrel. Patients were enrolled at 40 medical centers in the U.S., 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 with54 (5.9%) in the conventionally treated group at one year.
Pereira said that the reduction in the number of adverse events per patient also has important clinical implications. “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,” he said.
Among patients with the genetic variant, there were no differences in the safety endpoint of TIMI major bleeding (fatal bleeding, intracranial bleeding or any major bleeding) 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 one year.
One reason, Pereira noted, for the trial not achieving its primary endpoint could be improvement in standard of care following PCI (ie, drug-eluting stents) that has occurred over the 8 years since the trial was designed (2012). While the technology has vastly improved patient care, it may also have made it more difficult to reach the 505 reduction in adverse events based on the number of subjects enrolled.
The next step, he said, will be to analyze the cost effectiveness of genetically guided therapy. 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.
Pereira NL, et al. Joint American College of Cardiology and Journal of American College of Cardiology Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 28-30, 2020 (virtual meeting). ABSTRACT