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Original Investigation
January 13, 2020

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

Author Affiliations
  • 1Department of Pharmacy, Vancouver General Hospital, Vancouver, British Columbia, Canada
  • 2Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  • 3Division of Cardiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
  • 4Alberta SPOR Support Unit, University of Alberta, Edmonton, Alberta, Canada
  • 5Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada
  • 6Division of Nephrology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
JAMA Intern Med. Published online January 13, 2020. doi:10.1001/jamainternmed.2019.6447
Key Points

Question  What is the association between ticagrelor vs clopidogrel and major adverse coronary events, major bleeding, and dyspnea in patients with acute coronary syndrome treated with percutaneous coronary intervention?

Findings  In this cohort study of 11 185 patients, ticagrelor was not associated with a statistically significantly lower risk of major adverse coronary events compared with clopidogrel. However, it was associated with statistically significantly more major bleeding and dyspnea.

Meaning  Ticagrelor was not associated with a lower risk of major adverse coronary events in patients with acute coronary syndrome who underwent percutaneous coronary intervention.

Abstract

Importance  Guidelines currently recommend ticagrelor over clopidogrel for patients with acute coronary syndrome (ACS) based on randomized clinical trial data in which ticagrelor reduced major adverse coronary events (MACE) vs clopidogrel but increased bleeding and dyspnea.

Objective  To compare the risk of MACE with ticagrelor vs clopidogrel in patients with ACS treated with percutaneous coronary intervention (PCI), to compare major bleeding and dyspnea, and to evaluate the association between P2Y12 inhibitor adherence and MACE.

Design, Setting, and Participants  Population-based cohort study using data of patients discharged alive after PCI for ACS from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry from April 1, 2012, to March 31, 2016, with follow-up to 1 year. Analysis began April 2018.

Exposures  Outpatient prescription for ticagrelor or clopidogrel within 31 days after PCI. Adherence was defined as a medication refill adherence value of 80% or higher.

Main Outcomes and Measures  Major adverse coronary events, a composite of all-cause death, hospitalization for ACS, unplanned coronary revascularization, or stent thrombosis within 365 days after index PCI. Secondary outcomes included hospitalization for major bleeding and emergency department visit for dyspnea.

Results  Of 11 185 individuals who underwent PCI, the median (interquartile range) age was 61 (54-71) years, and 2760 (24.7%) were women. Ticagrelor users (4076 [36.4%]) were generally younger and had fewer cardiac and noncardiac comorbidities than clopidogrel users. Ticagrelor was not associated with lower risk of MACE (adjusted hazard ratio [aHR], 0.97; 95% CI, 0.85-1.10); however, it was associated with an increased risk of major bleeding (aHR, 1.51; 95% CI, 1.29-1.78) and dyspnea (aHR, 1.98; 95% CI, 1.47-2.65). A total of 3328 ticagrelor users (81.6%) were adherent during the study vs 5256 of clopidogrel users (73.9%) (P < .001; χ2 = 86.4). In the full cohort, adherence was associated with a lower MACE risk (aHR, 0.79; 95% CI, 0.69-0.90 for adherence of ≥80% vs <80%). Differences in other secondary outcomes were not statistically significant. Sensitivity and subgroup analyses were consistent with primary analyses.

Conclusions and Relevance  In this population-based cohort study of patients with ACS who underwent PCI, outpatient use of ticagrelor was not associated with a statistically significant reduction in MACE vs clopidogrel; however, it was associated with more major bleeding and dyspnea.

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