Ticagrelor after PCI was not associated with a significant reduction in MACE risk vs clopidogrel and was associated with more major bleeding and dyspnea among patients with ACS.
These findings, from a Canadian population-based cohort study, were published January 13, 2020 in JAMA Internal Medicine.
Ticagrelor is the more potent of the 2 P2Y12 inhibitors and, as authors state in describing the importance of their findings, is currently recommended by treatment guidelines over clopidogrel for use with aspirin in dual antiplatelet therapy. That recommendation is based largely on a pivotal 2009 trial that found greater post-PCI benefit with ticagrelor.
The authors, led by Ricky D. Turgeon, BSc(Pharm), PharmD, of the faculty of pharmaceutical sciences, University of British Columbia, Vancouver, British Columbia, Canada, note that at the time of the trial, PCI standard of care was using bare metal stents or first-generation drug-eluting stents.
The current cross-sectional study was based on data from patients discharged after PCI—performed primarily with second-generation drug-eluting stents—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 in April 2018.
The 11 185 individuals all received an outpatient prescription for either ticagrelor or clopidogrel within 31 days post-PCI and were assumed to be taking aspirin 81 mg daily during follow-up.
Primary outcome measures were MACE (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. The study also evaluated the association between P2Y12 inhibitor adherence and the primary outcome.
- Ticagrelor was not associated with lower risk of MACE vs clopidogrel: 10.3% vs 11.6% clopidogrel (adjusted HR 0.97, 95% CI 0.85-1.10)
- Ticagrelor was associated with increased risk of:
-- Major bleeding: 6.8% vs 6.3% (aHR 1.51, 95% CI 1.29-1.78)
-- Dyspnea: 2.9% vs 1.6% (aHR 1.98, 95% CI 1.47-2.65) _______________________________________________
Median age of participants was 61 years and one-quarter were women. Those taking ticagrelor (36.4%) were younger than clopidogrel users and presented with fewer comorbidities.
Ticagrelor users were more adherent with post-PCI P2Y12 inhibitor therapy, with prescription refill rates in the first year after discharge of 81.6% vs 73.9% for clopidogrel users (P<.001). Researchers also found that better adherence with therapy was associated with lower MACE risk (aHR 0.79, 95% CI 0.69-0.90), an association that was stronger than choice of the P2Y12 inhibitor itself.
“Our findings differ from prior studies on this topic, and this may be due to differences in methodology, patient populations and advances in interventional cardiology,” the authors wrote in the study. In their conclusion they state: “In aggregate, these study findings suggest that the increased potency of ticagrelor may not translate to improved efficacy in the era of second-generation drug-eluting stents, particularly after patients are hospital discharged.”
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