{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T06:19:36Z","timestamp":1792995576745,"version":"4.5.0"},"reference-count":77,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,2]],"date-time":"2018-12-02T00:00:00Z","timestamp":1543708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ticagrelor and prasugrel are third\u2010generation oral P2Y<jats:sub>12 <\/jats:sub>receptor antagonists with rapid onset and pronounced platelet inhibition. However, higher overall bleeding rates have been reported for these agents when compared with clopidogrel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To compare the risk of gastrointestinal bleeding (GIB) among users of third\u2010generation P2Y<jats:sub>12<\/jats:sub> inhibitors with clopidogrel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically searched for published randomised controlled trials of ticagrelor or prasugrel versus clopidogrel until September 2018. The primary outcome was the risk of GIB among users of third\u2010generation P2Y<jats:sub>12 <\/jats:sub>inhibitors when compared to clopidogrel, expressed as risk ratio (RR) and 95% confidence interval (CI). The rates of non\u2010coronary artery bypass graft (CABG) major bleeding, life\u2010threatening bleeding, fatal bleeding, and intracranial bleeding were analysed as secondary outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty\u2010one studies were included in the analysis of non\u2010CABG major bleeding, of which 12 were included in the analysis of GIB including 58\u00a0678 patients. Third\u2010generation P2Y<jats:sub>12<\/jats:sub> inhibitors were associated with higher risk of GIB as compared with clopidogrel (RR 1.28, 95% CI 1.13\u20101.46). The findings were consistent for upper (RR 1.32, 95% CI 1.05\u20101.67) and unspecified GIB (RR 1.25, 95% CI 1.01\u20101.53), but not lower GIB (RR 1.25, 95% CI 0.95\u20101.65). Subgroup analysis showed higher GIB risk in prasugrel studies (RR 1.40, 95% CI 1.10\u20101.77) than in ticagrelor studies (RR 1.15, 95% CI 0.94\u20101.39). Third\u2010generation P2Y<jats:sub>12<\/jats:sub> inhibitors also increased the risk of non\u2010CABG major bleeding (RR 1.18, 95% CI 1.08\u20101.28).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Third\u2010generation P2Y<jats:sub>12<\/jats:sub> inhibitors were associated with increased risk of GIB and non\u2010CABG major bleeding when compared with clopidogrel.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15059","type":"journal-article","created":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T04:03:28Z","timestamp":1543809808000},"page":"7-19","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Systematic review with meta\u2010analysis: the risk of gastrointestinal bleeding in patients taking third\u2010generation P2Y<sub>12<\/sub> inhibitors compared with clopidogrel"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0657-473X","authenticated-orcid":false,"given":"Chuan\u2010Guo","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther W.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Shing","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Medicine, Li Ka Shing Faculty of Medicine University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Isshiki","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Ageo Central General Hospital Ageo Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C. 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