Genotype tailoring of antiplatelet therapy provides no benefit: PCI study

One of the largest trials to investigate a CYP2C19 genotype-guided strategy to guide antiplatelet choice has found no benefit when applied to clopidogrel and ticagrelor after PCI.

The TAILOR-PCI study, which enrolled 5,302 patients requiring 12 months of antiplatelet therapy after PCI, failed to show any benefit from selecting therapy based on the presence of the CYP2C19 liver enzyme abnormality.

Patients who were genotyped as having the CYP2C19 abnormality, which may reduce an individual’s ability to metabolise clopidogrel and predispose to thrombosis, had the option to have therapy escalated to ticagrelor, which is not dependent on the CYP2C19 liver enzyme.

In the US study, patients were randomly assigned either to conventional therapy (clopidogrel 75 mg daily) or genotype-guided therapy (ticagrelor 90 mg twice daily for carriers and clopidogrel 75 mg daily for noncarriers).

But for the primary outcome of major adverse cardiovascular events there was no difference between treatment groups  at 12 months.

Among patients who carried the genetic variant, the primary endpoint occurred in 4% of the genotype-guided group, compared with 5.9% in the conventional group (hazard ratio, 0.66; p=0.056). No difference was seen in the safety endpoint of major bleeding or minor bleeding (1.9% vs. 1.6%, respectively).

However the investigators noted that when the time to multiple recurrent events was considered, there was a possible benefit with a genotype-guided strategy. In a prespecified sensitivity analysis for the primary endpoint, there was a 40% reduction for cumulative primary endpoint events that occurred during the study period (95% CI, 0.41-0.89; p=0.011).

“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 Dr Naveen Pereira of the Mayo Clinic in Rochester, Minnesota, co-principal investigator of the study.

Also, a post hoc analysis found a nearly 80% reduction in the rate of adverse events in the first three months of treatment among patients who received genetically guided therapy compared with those who did not.

“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.”

Current guidelines from the ACC and American Heart Association do not recommend testing patients for the CYP2C19 genetic abnormality before prescribing clopidogrel. 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.

The results of were presented March 28 during the virtual  ACC.20/WCC meeting

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