Abstract of the day - Real-world implementation of a genotype-guided P2Y12-inhibitor de-escalation strategy in ACS patients
01 Sep 2024
Abstract of the Day Around 15% of Caucasians and Africans and 30% of Asians carry a CYP2C19 loss-of-function (LoF) allele (CYP2C19*2 or CYP2C19*3),1 which can attenuate the conversion of clopidogrel to its active metabolite and increase the risk of major adverse cardiovascular events as compared to non-carriers.2
As presented today by Doctor Jaouad Azzahhafi (St Antonius Hospital - Nieuwegein, Netherlands), implementation of CYP2C19 genotyping to guide de-escalation of ticagrelor or prasugrel to clopidogrel was investigated in patients with acute coronary syndrome (ACS) in the FORCE-ACS registry. A total of 4,915 patients received standard dual antiplatelet therapy. From 2021, a genotype-guided strategy was implemented and this was applied to 406 patients: 34.7% of these were found to be carriers of the LoF alleles CYP2C19*2 or CYP2C19*3 and remained on ticagrelor or prasugrel, while 65.3% were non-carriers and switched from ticagrelor or prasugrel to clopidogrel. Ischaemic and bleeding outcomes were compared between the genotyped and the standard-care cohorts.
After one year, the primary ischaemic composite endpoint – cardiovascular mortality, myocardial infarction or stroke – occurred in 5.2% of patients in the genotyped cohort compared with 6.9% in the standard-care cohort (adjusted hazard ratio [HR] 0.88; 95% CI 0.56 to 1.38). The risk of the primary bleeding endpoint – BARC 2, 3 or 5 bleeding – was halved in patients in the genotyped cohort (4.7%) compared with the standard-care cohort (9.8%) (adjusted HR 0.50; 95% CI 0.31 to 0.78).
The results demonstrate the feasibility of a CYP2C19 genotype-guided de-escalation strategy for P2Y12 inhibitors in a real-world ACS population, with a reduction in bleeding events and no increase in ischaemic events compared with a standard treatment approach. According to the authors, this approach could help to personalise antiplatelet therapy, optimising patient outcomes, potentially reducing healthcare costs and enhancing patient compliance and satisfaction by reducing the side effects associated with more potent antiplatelet agents.
Further large-scale research is needed to confirm these findings. Upcoming studies will focus on expanding the genotype-guided strategy to a broader patient population and investigating its long-term benefits (including quality of life) and cost-effectiveness in various settings. In addition, studies exploring the integration of genotype-guided antiplatelet therapy with other personalised medicine approaches, such as risk-score guided treatment, are planned.
References
- Scott SA, et al. Clin Pharmacol Ther. 2013;94:317–323.
- Mega JL, et al. JAMA. 2010;304:1821–1830.
