Similar risk of NACE when comparing two P2Y12 inhibitors in patients with ACS after PCI
Association of Ticagrelor vs Clopidogrel With Net Adverse Clinical Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.
Introduction and methods
The P2Y12 inhibitor ticagrelor is a more potent platelet inhibitor than clopidogrel . Guidelines from the ACC, AHA, ESC, and EACTS recommend ticagrelor in combination with aspirin for patients with acute coronary syndrome (ACS) [2,3]. The recommendations are based on the PLATO-trial, which demonstrated that ticagrelor had a more profound effect in patients with ACS compared to clopidogrel [4-7]. However, in this trial the efficacy of ticagrelor was not observed in patients from North-America and Asia . Also safety concerns in regards to ticagrelor-induced dyspnea and increased hemorrhagic events observed with use of ticagrelor in routine practice have been raised .
This study assessed the association of ticagrelor (n=31,290) compared to clopidogrel (n=31,290) with clinical outcomes in patients from the United States and South-Korea diagnosed with ACS who underwent PCI.
This retrospective cohort study used the electronic health record (EHR)-based databases, US Optum EHR (n=32,828) and US IQVIA Hospital (n=7996) from the United States and the nationwide claims database Health Insurance Review and Assessment service (HIRA; n=21,756) from South-Korea. Adult patients (≥20 years) who underwent PCI for the first time after an ACS diagnosis were selected for the study. The index date was the date of PCI. Patients were matched using a large-scale propensity score algorithm resulting in 31,290 matched pairs. The primary outcome was net adverse clinical events (NACE) that included ischemic events (recurrent acute MI, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding) from the index date to 1 year after PCI. Secondary outcomes were a broader definition of NACE (NACE or mortality), all-cause mortality, composite ischemic events, composite hemorrhagic events, and individual outcomes from the primary endpoint within 1 year. The 1-year risk of dyspnea was also evaluated. A post-hoc analysis for CV-related mortality and MACE (CV mortality, recurrent acute MI, and stroke) was conducted using only the US Optum EHR and South-Korean HIRA databases. Follow-up period was from November 2011 to March 2019.
- The 1-year incidence of NACE in patients with ACS who underwent PCI was 15.1% (3484/23116 person-years) in the ticagrelor group compared to 14.6% (3290/22587 person-years) in the clopidogrel group (HR 1.05, 95% CI: 1.00-1.10, P=0.06).
- The incidence rate of NACE or mortality was comparable between patients treated with ticagrelor or clopidogrel (16.8% vs. 16.6%, respectively, HR 1.03, 95% CI: 0.98-1.08). There were also no differences observed in the risk for an ischemic event, ischemic stroke, acute MI, revascularization, or all-cause mortality.
- Patients treated with ticagrelor had, compared to patients receiving clopidogrel, a significantly higher risk of an hemorrhagic event (HR 1.35, 95% CI: 1.13-1.61, P=0.001), hemorrhagic stroke (HR 1.60, 95% CI: 1.10-2.33, P=0.01), or gastrointestinal bleeding (HR 1.32, 95% CI: 1.05-1.66, P=0.02).
- The 1-year risk of dyspnea was significantly increased in patients treated with ticagrelor compared to those on clopidogrel (HR 1.21, 95% CI: 1.17-1.26, P<0.001).
- There was no difference in CV-related mortality (HR 0.98, 95% CI: 0.76-1.26) and MACE (HR 1.05, 95% CI: 0.90-1.22) between the ticagrelor and clopidogrel groups.
Risk of NACE in patients using ticagrelor was comparable to that in patients on clopidogrel among patients from the US and South-Korea, who underwent a first time PCI after ACS diagnosis. Patients on ticagrelor had a higher risk of an hemorrhagic stroke or gastrointestinal bleeding and dyspnea compared to patients using clopidogrel.