Genotype-guided post-PCI antiplatelet therapy just missed significance in reducing ischemic events
Clinical Implementation Of Clopidogrel Pharmacogenetics: The Tailor PCI Trial
Presented at ACC.20 by Naveen Pereira, MD (Rochester, MN, US)
Introduction and methods
Clopidogrel is the most prescribed antiplatelet drug with aspirin after PCI. However, up to 30% of patients have CYP2C19 loss of function variants and are potentially resistant to clopidogrel therapy. Currently, guidelines do not recommend genetic testing due to absence of evidence from clinical trials. The TAILOR-PCI trial evaluated whether identification of CYP2C19 loss of function patients and changing antiplatelet therapy based on genotype reduced ischemic outcomes.
5,270 Patients with ACS and stable CAD who underwent PCI were randomized to either a point of care genotyping arm or to a conventional arm. In the genotyping arm, patients were identified with loss of function in CYP2C19 *2 & *3. Those patients were treated with ticagrelor 90mg BID. Patients with wildtype (WT) CYP2C19 received clopidogrel, 75mg daily. In the conventional arm, all patients received clopidogrel. Primary outcomes were heart attack, stroke, cardiac death, severe recurrent ischemia, stent thrombosis and safety outcomes were major or minor bleeding, assessed during 1-year follow-up.
The investigators assumed a 50% reduction in ischemic events when genetic testing was used to identify patient with CYP2C19 loss of function variants and treat those patients with alternative antiplatelet therapy.
- Risk for the primary endpoint of heart attack, stroke, cardiac death, severe recurrent ischemia and stent thrombosis after 1-year follow-up was reduced with 34% in the genotype-guided treatment arm compared to the conventional therapy arm. However, the P-value was statistically not significant (P=0.056).
- A post-hoc analysis showed a risk reduction of 80% in the first three months after randomization in the genotype-guided therapy arm compared with the conventional therapy arm (P=0.001).
- Pre-specified analyses for multiple recurrent events showed a 40% reduction in ischemic events with genotype-guided treatment compared to conventional treatment (P=0.011).
- No differences between the two arms were found for the safety outcome of major and minor bleeding.
The strategy to use point-of-care genotyping to identify CYP2C19 loss of function patients to guide antiplatelet therapy did not reduce the primary endpoint by 50% compared with conventional clopidogrel therapy. However, a 34% risk reduction for the primary endpoint was found at one year in the genotype-guided therapy arm compared with the conventional therapy arm. Furthermore, a potential benefit was greatest within 3 months after PCI and a pre-specified analysis suggested a benefit for reducing multiple recurring ischemic events over 12 months in patients in the genotype-guided therapy arm compared to the conventional arm. Major and minor bleeding rates were similar between both treatment arms.
The discussant Roxana Mehran, MD noted that although this study unfortunately missed its goal to reduce ischemic events by 50%, the investigators found a 34% reduction. This is a clinically relevant reduction, according to Mehran. Furthermore, in the important vulnerable period of up to 3 months after PCI, an important early benefit was found with genotype-guided therapy. Mehran stated that in her opinion, this study showed that tailoring therapy using genotyping and treating the patients appropriately was beneficial in this patient population.
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