Association of Ticagrelor vs Clopidogrel With Major Adverse Coronary Events in Patients With Acute Coronary Syndrome Undergoing 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 P2Y 12 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 MEASURESMajor 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. RESULTSOf 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; χ 2 = 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 Ն80% vs <80%). Differences in other secondary outcomes were not statistically significant. Sensitivity and subgroup analyses were consistent with primary analyses. CONCLUSIONS AND RELEVANCEIn 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.

Effects of clopidogrel, prasugrel and ticagrelor on prevention of stent thrombosis in patients underwent percutaneous coronary intervention: A network meta‐analysis

“…More interestingly, several recent real‐world studies actually found that ticagrelor was not superior to clopidogrel for preventing ST, 38‐40 which was different from PLATO trial as well as our study. This might be explained by the following reasons.…”

“…This might be explained by the following reasons. A potent mediator for efficacy attenuation of ticagrelor outside RCT might be decreased compliance because of the higher rate of adverse events (dyspnea, bleeding), administration of the drug twice daily and higher costs 38‐40 . Additionally, the overall improvement in the clinical outcomes of patients with ACS 41 might be another possible explanation for the diminished benefit of ticagrelor in the modern era; particularly, this might be driven by progress in the use of drug‐eluting stents 42 and poststenting care.…”

P2Y12 Inhibitor Utilization for Acute Coronary Syndrome in the Elderly: A Provincial Analysis From 2008 to 2018

“…This is not dissimilar to the previously published real-world data; Schwalm et al reported a 92% compliance in P2Y12 inhibitor prescriptions after PCI in a cluster RCT, while and Turgeon et al demonstrated a 80.5% compliance rate in their cohort of 13,897 ACS patients treated with PCI in Alberta from 2012 to 2016. (28,29) Esposti et al analysed discharge prescriptions of 1,882 ACS patients in Italy. Of the 83% of patients who were discharged on any antiplatelet therapy, 57% were prescribed ASA and clopidogrel and only 0.1% of patients were discharged on ASA and ticagrelor.…”

Evidence-based approaches to comparing the effectiveness of modern cardiology interventions: trends, bias and prospects

“…В качестве примера можно отметить неожиданные результаты ретроспективного анализа баз данных страховых компаний, который был выполнен в Германии с использованием метода PS [30]. В ходе выполнения анализа, включавшего данные о 37439 пациентах с ФП, были получены данные о том, что прием варфарина по сравнению с ППОАК сопровож дается меньшей часто- [31]. Полученные результаты свидетельствовали о том, что применение тикагрелора в клинической практике не имеет преимуществ по сравнению с приемом клопидогрела по влиянию на риск развития тяжелых осложнений коронарной болезни сердца в течение года после стентирования коронарной артерии по поводу острого коронарного синдрома.…”