Does ticagrelor lower the risk of MACE in patients of ACS undergoing PCI?

US: The recommendation to prescribe ticagrelor over clopidogrel in dual antiplatelet therapy for patients with an acute coronary syndrome (ACS) largely derives from the randomized PLATO trial, in which ticagrelor was associated with lower relative risks for major adverse coronary events (MACE) and death (16% and 22%, respectively) but with higher relative risks for major bleeding and dyspnea (19% and 84%, respectively).

Ticagrelor's benefits, however, were not seen in the North American cohort, which the authors later attributed to the higher aspirin dose commonly used in this region. The current investigators leveraged a Canadian population-based registry to determine the real-world comparative effectiveness of ticagrelor and clopidogrel in an area with universal healthcare access.

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 was conducted from April 1, 2012, to March 31, 2016, with follow-up to 1 year. The analysis began in April 2018.

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.

In this study, ticagrelor was not significantly associated with the reduction in MACE in comparison to clopidogrel; however, it was associated with more major bleeding(hazard ratio-1.51) and dyspnea(hazard ratio-1.98), raising questions about the superiority of ticagrelor for patients undergoing PCI for ACS. There are many potential reasons for this study's discordance with PLATO, including study design, study population, and advances in stent design. These results, while not practice-changing, are strong enough to raise doubts. We need additional investigations to clarify the effectiveness of this increasingly prescribed medication.

For further reading follow,

Turgeon RD et al. Association of ticagrelor vs clopidogrel with major adverse coronary events in patients with acute coronary syndrome undergoing percutaneous coronary intervention. JAMA Intern Med 2020 Mar; 180:420. (https://doi.org/10.1001/jamainternmed.2019.6447)