Hospitalization for Myocardial Infarction with Ticagrelor or Clopidogrel in Patients with Acute Coronary Syndrome: An On-Treatment Comparative Effectiveness Analysis

Abstract

Introduction: Prescribing patterns and suboptimal adherence present methodological challenges for real-world head-to-head comparisons of ticagrelor and clopidogrel in intent-to-treat studies. The aim of this study was to compare ticagrelor and clopidogrel in an on-treatment population. Methods: This retrospective cohort study used the Optum TM Clinformatics TM database to identify patients with acute coronary syndrome (ACS) discharged on ticagrelor or clopidogrel between January 1, 2012 and September 30, 2019. The primary end point was hospitalization for myocardial infarction (MI); the secondary end point was hospitalization for major bleeding. The ticagrelor and clopidogrel cohorts were balanced by propensity score matching (PSM) 1:3 for demographic and clinical characteristics. Outcomes were ascertained from day 31 until day 365 or end of follow-up.Results: Of 339,387 patients with ACS, 14,110 ticagrelor-and 57,482 clopidogrel-treated patients met the study criteria. After PSM, 13,373 ticagrelor-and 29,656 clopidogrel-treated patients provided 4945 and 13,895 patientyears of data, respectively, for the primary end point. Hospitalization for MI was significantly lower in the ticagrelor compared to the clopidogrel cohort (2.22 vs. 3.52 per 100 patientyears; 36.8% relative risk reduction [RRR]; P \ 0.0001). Hospitalization for major bleeding was similar in the ticagrelor and clopidogrel cohorts (2.04 vs. 2.06 per 100 patient-years; 1.1% RRR, P = 0.9214). Conclusions: In this real-world on-treatment analysis, hospitalization for MI was significantly lower with ticagrelor compared to clopidogrel, with similar rates of hospitalization for major bleeding. Study findings underscore the importance of being on the appropriate guidelinerecommended therapy and support the use of ticagrelor over clopidogrel.

Comparative Safety and Effectiveness of Ticagrelor versus Clopidogrel in Patients With Acute Coronary Syndrome: An On-Treatment Analysis From a Multicenter Registry

“…Despite a sub-analysis from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, more bleeding occurred with ticagrelor than with clopidogrel, as in our study, when patients with a history of major bleeding, prior to hemorrhagic stroke, and those receiving dialyses were excluded from the analysis, no significant difference in the risk of bleeding was found between treatment groups ( 5 ). These findings should be put into perspective with those from recent studies, some of them indicating a reduction in MACE in favor of ticagrelor ( 5 , 16 , 30 , 31 ), others finding neither difference in mortality nor in MACE ( 7 – 11 , 28 ), with the overwhelming majority observing an increased risk of bleeding with ticagrelor vs. clopidogrel ( 5 – 11 ). Nonetheless, the underlying reasons for these contradictory results are still unclear.…”

“…Nevertheless, despite the inherent limitations of ITT analysis in observational research, not enough attention has been paid to assessing the comparative safety and effectiveness of P2Y 12 inhibitors according to the on-treatment principle. Furthermore, the time-varying nature of exposure has been systematically ignored by recent retrospective studies in the field, with the consequent risk of selection bias ( 9 , 31 ).…”

Ticagrelor versus clopidogrel for recurrent myocardial infarction: An outcomes-based agreement

“…Hospitalization for MI was significantly lower in the ticagrelor compared to the clopidogrel cohort (2.22 versus 3.52 per 100 patient-years; 36.8% relative risk reduction [RRR]; P < 0.0001). 10 …”