Al-Rubaish, AM; Al-Muhanna, FA; Alshehri, AM; Al-Mansori, MA; Alali, RA; Khalil, RM; Al-Faraidy, KA; ... Al-Ali, AK; + view all Al-Rubaish, AM; Al-Muhanna, FA; Alshehri, AM; Al-Mansori, MA; Alali, RA; Khalil, RM; Al-Faraidy, KA; Cyrus, C; Sulieman, MM; Vatte, C; Loza, BL; Claassens, DMF; Asselbergs, FW; Al-Ali, AK; - view fewer (2021) Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients. International Journal of Cardiology 10.1016/j.ijcard.2021.08.051. (In press).

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Abstract

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. METHODS: This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. RESULTS: STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). CONCLUSION: A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy.

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