Net clinical benefit of clopidogrel versus ticagrelor in elderly patients carrying CYP2C19 loss-of-function variants with acute coronary syndrome after percutaneous coronary intervention

Background and aims: Elderly patients with acute coronary syndrome (ACS) tend to choose clopidogrel over potent P2Y12 receptor inhibitor such as ticagrelor after percutaneous coronary intervention (PCI) in China considering higher risks of bleeding. CYP2C19 genotype is regarded as a major factor influencing the efficacy of clopidogrel. The present study aims to investigate the efficacy and safety of ticagrelor relative to clopidogrel in elderly ACS patients after PCI in China with reduced CYP2C19 metabolism.

Methods: Between January 2016 and March 2019, 2751 ACS patients over 65 years old with CYP2C19 loss-of-function (LOF) variants after PCI were enrolled. All patients were treated with aspirin and P2Y12 receptor inhibitor, among whom 2056 received clopidogrel and 695 received ticagrelor. Net adverse clinical events (NACE), a composite of cardiac death, myocardial infarction (MI), ischemic stroke, target vessel revascularization and clinically relevant bleeding including Bleeding Academic Research Consortium (BARC) types 2, 3, 5 bleeding, were compared between the two groups at 12 months after PCI. Propensity score matching (PSM) was conducted to balance the baseline characteristics between the two groups.

Results: Before and after PSM, NACE was significantly increased in ticagrelor group compared with clopidogrel group at 12 months post PCI (Before PSM, 15.18% vs. 25.61% p<0.001; After PSM, 11.66% vs. 26.01% p<0.001). MACE was comparable between the two groups (Before PSM, 5.45% vs. 5.32% p>0.999; After PSM, 3.59% vs. 5.38% p=0.146). BARC types 2, 3, 5 bleeding events were significantly increased in patients treated with ticagrelor relative to clopidogrel (Before PSM, 10.31% vs. 21.01% p<0.001; After PSM, 8.22% vs. 21.38% p<0.001), which was mainly attributed to a higher incidence of BARC type 2 bleeding events in ticagrelor group (Before PSM, 8.12% vs. 18.56% p<0.001; After PSM, 6.43% vs. 18.83% p<0.001).

Conclusions: In the present real-world study, selection of ticagrelor over clopidogrel showed a significant increase in NACE with a higher incidence of bleeding and similar ischemic events in elderly ACS patients carrying CYP2C19 LOF variants after PCI.