Associations of outpatient use of P2Y12 inhibitors with MACE in ACS patients after PCI

Association of Ticagrelor vs Clopidogrel With Major Adverse Coronary Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Literature - Turgeon RD, Koshman SL, Youngson E et al., - JAMA Intern Med. 2020. doi:10.1001/jamainternmed.2019.6447.

Introduction and methods

The PLATO trial has shown that treatment with ticagrelor in ACS patients resulted in a 16% relative risk reduction in MACE and 22% relative risk reduction in all-cause death compared to treatment with clopidogrel [1]. However, ticagrelor was also associated with a relative risk increase by 19% for major bleeding and by 84% in dyspnea compared to clopidogrel. Current ACC/AHA and Canadian guidelines recommend ticagrelor over clopidogrel in DAPT [2,3]. Patients in routine practice may have higher risks of MACE and bleeding, more comorbidities and lower adherence to therapy than patients enrolled in clinical trials [4].

This observational study therefore evaluated the association between ticagrelor vs clopidogrel and MACE, major bleeding and dyspnea in a population-based cohort of patients with ACS who underwent PCI. Outpatient prescription data and prescription filling for ticagrelor or clopidogrel from 11,185 patients who underwent PCI for ACS were analyzed. 63.6% Used clopidogrel and 56.3% used ticagrelor. All patients used acetylsalicylic acid, 81 mg. Median age was 61 (54-71) years, 24.7% were women and 44.3% presented with STEMI. Follow-up was 1 year.

The primary outcome was first occurrence of MACE, defined as a composite of all-cause death, hospitalization with nonfatal ACS, coronary revascularization or stent thrombosis within 1 year after index hospitalization. Adherence was estimated using the (medical refill adherence [MRA].

Main results

  • Multivariable adjusted analyses showed no significant difference in MACE between ticagrelor and clopidogrel (adjusted HR [aHR]: 0.97, 95%CI, 0.85-1.10).
  • Ticagrelor was associated with a significantly higher risk of major bleeding (aHR: 1.51, 95%CI 1.29-1.78), which was mainly driven by a significantly higher risk of gastrointestinal hemorrhage (aHR: 2.02, 95%CI 1.52-2.68) and pulmonary hemorrhage (aHR: 1.49, 95%CI 1.15-1.93).
  • Ticagrelor was also associated with a significantly higher risk of an emergency department visit for dyspnea (aHR: 1.98, 95%CI 1.47-2.65).
  • Adherence to P2Y12 inhibitor therapy during the entire study was higher in ticagrelor users compared to clopidogrel users (81.6% vs 73.9%, P<0.001, χ²=86.4).
  • In the complete cohort, MACE was significantly lower in patients with P2Y12 inhibitor adherence of ≥80%, compared with adherence <80% (aHR: 0.79, 95%CI 0.69-0.90).


This observational population-based cohort study of patients with ACS who underwent PCI and received DAPT, showed no significant difference in MACE between patients treated with ticagrelor or clopidogrel. However, ticagrelor was associated with a higher risk of major bleeding and emergency room visits for dyspnea. Adherence to any P2Y12 inhibitor (MRA≥80%) was associated with a significantly lower risk of MACE compared with adherence <80%.


1. Wallentin L, Becker RC, Budaj A, et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057. doi:10.1056/NEJMoa0904327

2. Mehta SR, Bainey KR, CantorWJ, et al; members of the Secondary Panel. 2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology focused update of the guidelines for the use of antiplatelet therapy. Can J Cardiol. 2018;34(3):214-233. doi:10.1016/j.cjca.2017.12.012

3. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Circulation. 2016; 134(10):e123-e155. doi:10.1161/CIR.0000000000000404

4. Kennedy-Martin T, Curtis S, Faries D, Robinson S, Johnston J. A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results. Trials. 2015;16(1):495. doi:10.1186/s13063-015-1023-4

Find this article online on JAMA Intern Med.

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