iRight4Me: individualisation of P2Y12 inihibitors in the realworld practice - an interim report

Abstract Background The uptake of CYP2C19 testing has been limited, as clinicians opined majority of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary interventions (PCI) should receive Ticagrelor per international guidelines. Remaining minority with high bleeding risk (HBR) would be on Clopidogrel from the outset. We set out to study how clinicians’ knowledge of CYP2C19 phenotype affects choice of P2Y12 inhibitors, and thus real-world clinical outcomes for ACS patients. We report the interim findings of bleeding at 6 months in the Ticagrelor-loaded subgroup. Methods Patients eligible for escalation or de-escalation were recruited into the study and tested for CYP2C19 polymorphism. CYP2C19 phenotype results and recommendations were revealed to outpatient clinicians, giving them the choice to keep or switch P2Y12 inhibitors. Bleeding outcomes were prospectively tracked and adjudicated by independent study team members. Results A total of 740 patients who have completed 6 months from index admission for ACS were used for this analysis. Overall adjudicated MACCE and bleeding rates were 3.46% (n = 27) and 12.7% (n=95) respectively. CYP2C19 Non-LoF (Loss-of-Function) patients who were de-escalated to Clopidogrel were least likely to bleed (Fig 1). Ticagrelor-only patients experienced almost twice the risk of bleeding than those who were de-escalated to Clopidogrel, regardless of phenotype status (15.1% vs 7.8%, Cox HR, p = 0.042). High bleeding risk (HBR) factors did not explain for differences in bleeding. The non-LoF patients on Ticagrelor (n = 173) experienced more than 2-fold risk of bleeding compared to those de-escalated to Clopidogrel (n = 71), adjusted HR 0.389, p = 0.059. MACCE rates were similar between these two groups at 2.41% for Non-LoF continued on Ticagrelor (n = 164) and 2.44% for Non-LoF switched to Clopidogrel (n = 81) respectively. Conclusion Our interim analysis shows that Ticagrelor is associated with significantly higher rates of bleeding which could be mitigated by de-escalation to Clopidogrel. Non-LoF patients who have been de-escalated to Clopidogrel could be at much lower risk of bleeding, without losing out on MACCE outcomes. CYP2C19 phenotype status has the potential to add more precision to decision-making. We expect to report final results of 1000 patients at the end of 12 months to fully assess the impact of phenotype-guided de-escalation on bleeding and MACCE.