Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

Int J Cardiol. 2021 Nov 15:343:15-20. doi: 10.1016/j.ijcard.2021.08.051. Epub 2021 Sep 11.

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.

Keywords: CYP2C19; Clopidogrel; P2Y12 inhibitor; PCI; STEMI; Ticagrelor.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / genetics
  • Humans
  • Myocardial Infarction* / diagnosis
  • Myocardial Infarction* / drug therapy
  • Myocardial Infarction* / genetics
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors
  • Point-of-Care Testing
  • Prospective Studies
  • ST Elevation Myocardial Infarction* / diagnosis
  • ST Elevation Myocardial Infarction* / drug therapy
  • ST Elevation Myocardial Infarction* / genetics
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19