{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:43:18Z","timestamp":1792510998908,"version":"4.5.0"},"reference-count":172,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000664","name":"National Institute for Health and Care Research (NIHR) Health Technology Assessment programme","doi-asserted-by":"publisher","award":["14\/192\/89"],"award-info":[{"award-number":["14\/192\/89"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"Background<\/jats:title>\nBleeding among populations undergoing percutaneous coronary intervention or coronary artery bypass grafting and among conservatively managed patients with acute coronary syndrome exposed to different dual antiplatelet therapy and triple therapy (i.e. dual antiplatelet therapy plus an anticoagulant) has not been previously quantified.<\/jats:p>\n<\/jats:sec>\nObjectives<\/jats:title>\nThe objectives were to estimate hazard ratios for bleeding for different antiplatelet and triple therapy regimens, estimate resources and the associated costs of treating bleeding events, and to extend existing economic models of the cost-effectiveness of dual antiplatelet therapy.<\/jats:p>\n<\/jats:sec>\nDesign<\/jats:title>\nThe study was designed as three retrospective population-based cohort studies emulating target randomised controlled trials.<\/jats:p>\n<\/jats:sec>\nSetting<\/jats:title>\nThe study was set in primary and secondary care in England from 2010 to 2017.<\/jats:p>\n<\/jats:sec>\nParticipants<\/jats:title>\nParticipants were patients aged \u2265 18 years undergoing coronary artery bypass grafting or emergency percutaneous coronary intervention (for acute coronary syndrome), or conservatively managed patients with acute coronary syndrome.<\/jats:p>\n<\/jats:sec>\nData sources<\/jats:title>\nData were sourced from linked Clinical Practice Research Datalink and Hospital Episode Statistics.<\/jats:p>\n<\/jats:sec>\nInterventions<\/jats:title>\nCoronary artery bypass grafting and conservatively managed acute coronary syndrome: aspirin (reference) compared with aspirin and clopidogrel. Percutaneous coronary intervention: aspirin and clopidogrel (reference) compared with aspirin and prasugrel (ST elevation myocardial infarction only) or aspirin and ticagrelor.<\/jats:p>\n<\/jats:sec>\nMain outcome measures<\/jats:title>\nPrimary outcome: any bleeding events up to 12 months after the index event. Secondary outcomes: major or minor bleeding, all-cause and cardiovascular mortality, mortality from bleeding, myocardial infarction, stroke, additional coronary intervention and major adverse cardiovascular events.<\/jats:p>\n<\/jats:sec>\nResults<\/jats:title>\nThe incidence of any bleeding was 5% among coronary artery bypass graft patients, 10% among conservatively managed acute coronary syndrome patients and 9% among emergency percutaneous coronary intervention patients, compared with 18% among patients prescribed triple therapy. Among coronary artery bypass grafting and conservatively managed acute coronary syndrome patients, dual antiplatelet therapy, compared with aspirin, increased the hazards of any bleeding (coronary artery bypass grafting: hazard ratio 1.43, 95% confidence interval 1.21 to 1.69; conservatively-managed acute coronary syndrome: hazard ratio 1.72, 95% confidence interval 1.15 to 2.57) and major adverse cardiovascular events (coronary artery bypass grafting: hazard ratio 2.06, 95% confidence interval 1.23 to 3.46; conservatively-managed acute coronary syndrome: hazard ratio 1.57, 95% confidence interval 1.38 to 1.78). Among emergency percutaneous coronary intervention patients, dual antiplatelet therapy with ticagrelor, compared with dual antiplatelet therapy with clopidogrel, increased the hazard of any bleeding (hazard ratio 1.47, 95% confidence interval 1.19 to 1.82), but did not reduce the incidence of major adverse cardiovascular events (hazard ratio 1.06, 95% confidence interval 0.89 to 1.27). Among ST elevation myocardial infarction percutaneous coronary intervention patients, dual antiplatelet therapy with prasugrel, compared with dual antiplatelet therapy with clopidogrel, increased the hazard of any bleeding (hazard ratio 1.48, 95% confidence interval 1.02 to 2.12), but did not reduce the incidence of major adverse cardiovascular events (hazard ratio 1.10, 95% confidence interval 0.80 to 1.51). Health-care costs in the first year did not differ between dual antiplatelet therapy with clopidogrel and aspirin monotherapy among either coronary artery bypass grafting patients (mean difference \u00a394, 95% confidence interval \u2013\u00a3155 to \u00a3763) or conservatively managed acute coronary syndrome patients (mean difference \u00a3610, 95% confidence interval \u2013\u00a3626 to \u00a31516), but among emergency percutaneous coronary intervention patients were higher for those receiving dual antiplatelet therapy with ticagrelor than for those receiving dual antiplatelet therapy with clopidogrel, although for only patients on concurrent proton pump inhibitors (mean difference \u00a31145, 95% confidence interval \u00a3269 to \u00a32195).<\/jats:p>\n<\/jats:sec>\nConclusions<\/jats:title>\nThis study suggests that more potent dual antiplatelet therapy may increase the risk of bleeding without reducing the incidence of major adverse cardiovascular events. These results should be carefully considered by clinicians and decision-makers alongside randomised controlled trial evidence when making recommendations about dual antiplatelet therapy.<\/jats:p>\n<\/jats:sec>\nLimitations<\/jats:title>\nThe estimates for bleeding and major adverse cardiovascular events may be biased from unmeasured confounding and the exclusion of an eligible subgroup of patients who could not be assigned an intervention. Because of these limitations, a formal cost-effectiveness analysis could not be conducted.<\/jats:p>\n<\/jats:sec>\nFuture work<\/jats:title>\nFuture work should explore the feasibility of using other UK data sets of routinely collected data, less susceptible to bias, to estimate the benefit and harm of antiplatelet interventions.<\/jats:p>\n<\/jats:sec>\nTrial registration<\/jats:title>\nThis trial is registered as ISRCTN76607611.<\/jats:p>\n<\/jats:sec>\nFunding<\/jats:title>\nThis project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment<\/jats:italic>; Vol. 27, No. 8. See the NIHR Journals Library website for further project information.<\/jats:p>\n<\/jats:sec>","DOI":"10.3310\/mnjy9014","type":"journal-article","created":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T10:30:42Z","timestamp":1689157842000},"page":"1-257","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Bleeding risk in patients prescribed dual antiplatelet therapy and triple therapy after coronary interventions: the ADAPTT retrospective population-based cohort studies"],"prefix":"10.3310","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4605-7710","authenticated-orcid":true,"given":"Jessica","family":"Harris","sequence":"first","affiliation":[{"name":"Bristol Trials Centre, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7097-8950","authenticated-orcid":true,"given":"Koen 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