{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:12:57Z","timestamp":1770509577051,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,7,10]],"date-time":"2013-07-10T00:00:00Z","timestamp":1373414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to investigate the associations between proton pump inhibitor (<jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content>) usage patterns and risk of severe gastrointestinal events in patients treated with low\u2010dose acetylsalicylic acid (<jats:styled-content style=\"fixed-case\">LDA<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and setting<\/jats:title><jats:p>A nationwide cohort study in Sweden.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>All Swedish residents \u226540\u00a0years of age, without cancer and receiving <jats:styled-content style=\"fixed-case\">LDA<\/jats:styled-content> treatment (\u226580% adherence for 365\u00a0days between 2005 and 2009) were identified in the Swedish Prescription Register. Continuous <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> use was defined as &gt;60 of 90\u00a0days covered by daily <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> doses and further divided into high (\u226580%) or moderate (&lt;80) adherence. All other <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> use was defined as intermittent use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main outcome measures<\/jats:title><jats:p>The risk of a combined end\u2010point of gastrointestinal ulcer or bleeding was analysed using Cox proportional hazard models. We also investigated risk of &gt;45\u00a0days of <jats:styled-content style=\"fixed-case\">LDA<\/jats:styled-content> treatment interruption.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During a median follow\u2010up of 2.5\u00a0years, 7880 of 648\u00a0807 (1.2%) <jats:styled-content style=\"fixed-case\">LDA<\/jats:styled-content>\u2010treated patients experienced gastrointestinal events. In multivariable\u2010adjusted models, both intermittent\u2010<jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> and no\u2010<jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> use were associated with increased risk of gastrointestinal ulcers or bleeding compared with continuous <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> use with a high level of adherence [hazard ratio (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>) 1.83 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.66\u20132.02) and 1.14 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.05\u20131.23), respectively]. Amongst continuous <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> users, moderate adherence also increased the risk of gastrointestinal ulcers or bleeding [<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> 1.22 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.07\u20131.40)]. The risk of <jats:styled-content style=\"fixed-case\">LDA<\/jats:styled-content> treatment interruption was higher with intermittent <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> use [<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> 1.16 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.14\u20131.19)] than continuous <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> use with high adherence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this large cohort of <jats:styled-content style=\"fixed-case\">LDA<\/jats:styled-content> users, intermittent <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> use was associated with higher risk of gastrointestinal ulcers or bleeding and interrupted <jats:styled-content style=\"fixed-case\">LDA<\/jats:styled-content> treatment, compared with continuous <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> use.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12103","type":"journal-article","created":{"date-parts":[[2013,6,26]],"date-time":"2013-06-26T08:36:43Z","timestamp":1372235803000},"page":"371-380","source":"Crossref","is-referenced-by-count":12,"title":["Low\u2010dose acetylsalicylic acid and gastrointestinal ulcers or bleeding \u2013 a cohort study of the effects of proton pump inhibitor use patterns"],"prefix":"10.1111","volume":"274","author":[{"given":"J.","family":"Hedberg","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Sundstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Uppsala Clinical Research Center Uppsala University Uppsala 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