Genotyping Improves Choice of Antithrombotic Regimen After Coronary Stenting: Presented at ESC

By Frances Morin

PARIS -- September 5, 2019 -- Selecting an oral P2Y12 inhibitor with genetic guidance for patients who have undergone primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) allows for a reduced risk of bleeding without increasing thrombotic event risk, according to a study presented here at the 2019 European Society of Cardiology (ESC) Congress.

“These findings show that physicians can reduce bleeding complications by using a genotype-guided strategy for selecting oral P2Y12 inhibitors in patients with STEMI without increasing the thrombotic risk,” said Jurrien M. ten Berg, MD, St. Antonius Hospital, Nieuwegein, the Netherlands.

Although ticagrelor and prasugrel are considered more effective in preventing thrombotic events after PCI compared with clopidogrel, they also have a higher risk of bleeding complications. However, some patients are carriers of the CYP2C19*2 and *3 loss-of-function alleles, which impair the conversion of clopidogrel in the liver.

To determine if a genotyping strategy could help to identify patients who could have a safe and sufficient response to clopidogrel, the researchers randomised 2,488 patients undergoing PCI for STEMI at 10 centres in the Netherlands, Belgium, and Italy to treatment with a P2Y12 inhibitor based on the results of early CYP2C19 genetic testing or to standard treatment with either ticagrelor or prasugrel for 12 months.

In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, while noncarriers of the allele received clopidogrel.

The first primary outcome was net adverse clinical events, defined as death from any cause, myocardial infarction (MI), definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes criteria. At 12 months, this primary endpoint occurred in 63 (5.1%) patients in the genotype-guided group and in 73 (5.9%) patients in the standard treatment group, establishing non-inferiority.

The second primary outcome of major or minor bleeding at 12 months was significantly lower in the genotype-guided group, occurring in 122 (9.8%) patients compared with 156 (12.5%) patients in the standard treatment group (hazard ratio = 0.78; P = .04).

There were no significant differences in terms of a secondary thrombotic outcome without bleeding, death from vascular causes, MI, definite stent thrombosis, or stroke. Those rates were 2.7% in the genotype-guided arm and 3.3% in the standard treatment arm.

“We found that genotyping is easy to use, can be done in the cath lab, and has fast results,” said Dr. Berg. “The results show that almost two-thirds of the patients could be treated with clopidogrel, with no differences in thrombotic event rates and a reduction in bleeding event rates.”

[Presentation title: Popular Genetics - Genotype-Guided Oral P2Y12-Inhibition in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI: a Randomized, Open-Label, Multicenter Trial. Abstract 6047]

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