{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:06Z","timestamp":1787013906333,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010152912"],"award-info":[{"award-number":["PJT\u2010152912"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The effect of tramadol on the cardiovascular system is largely unknown. There is concern that, with its multimodal mechanism of action to increase serotonin and norepinephrine levels in the body, it could increase the risk of arterial ischaemia and cardiovascular events. We aimed to compare the short\u2010term risk of cardiovascular events with the use of tramadol to that of codeine among patients with non\u2010cancer pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective population\u2010based cohort study using data from the Clinical Practice Research Datalink (CPRD) with new users of tramadol or codeine from April 1998 to March 2017. Exposure was defined using an approach analogous to an intention\u2010to\u2010treat, with a maximum follow\u2010up of 30\u2009days. The primary endpoint was myocardial infarction, and secondary endpoints were unstable angina, ischaemic stroke, coronary revascularization, cardiovascular death and all\u2010cause mortality. Hazard ratios (HRs) were estimated using Cox proportional hazards models, adjusted for high\u2010dimensional propensity score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The final cohort included 123\u2009394 tramadol users and 914\u2009333 codeine users. When tramadol was compared to codeine, the adjusted hazard ratio (HR) of myocardial infarction was 1.00 (95% CI 0.81\u20131.24). There was also no evidence of elevated risks of unstable angina (0.92; 95% CI 0.67\u20131.27), ischaemic stroke (0.98; 95% CI 0.82\u20131.17), coronary revascularization (0.97; 95% CI 0.69\u20131.38), cardiovascular death (1.07; 95% CI 0.93\u20131.23) or all\u2010cause mortality (1.03; 95% CI 0.94\u20131.14) when tramadol was compared to codeine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Short\u2010term use of tramadol, compared with codeine, was not associated with an increased risk of cardiac events among patients with non\u2010cancer pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.15099","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T06:42:52Z","timestamp":1633329772000},"page":"1824-1834","source":"Crossref","is-referenced-by-count":10,"title":["Tramadol versus codeine and the short\u2010term risk of cardiovascular events in patients with non\u2010cancer pain: A population\u2010based cohort study"],"prefix":"10.1111","volume":"88","author":[{"given":"Linda B.","family":"Ou","sequence":"first","affiliation":[{"name":"Department of Pharmacy Sunnybrook Health Sciences Centre  Toronto ON Canada"},{"name":"Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5162-3556","authenticated-orcid":false,"given":"Laurent","family":"Azoulay","sequence":"additional","affiliation":[{"name":"Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital McGill University  Montreal QC Canada"},{"name":"Department of Epidemiology, Biostatistics, and Occupational Health McGill University  Montreal QC Canada"},{"name":"Gerald Bronfman Department of Oncology McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Reynier","sequence":"additional","affiliation":[{"name":"Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Platt","sequence":"additional","affiliation":[{"name":"Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital McGill University  Montreal QC Canada"},{"name":"Department of Epidemiology, Biostatistics, and Occupational Health McGill University  Montreal QC Canada"},{"name":"Department of Pediatrics McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Yoon","sequence":"additional","affiliation":[{"name":"Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Grad","sequence":"additional","affiliation":[{"name":"Department of Family Medicine McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6055-0088","authenticated-orcid":false,"given":"Kristian B.","family":"Filion","sequence":"additional","affiliation":[{"name":"Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital McGill University  Montreal QC Canada"},{"name":"Department of Epidemiology, Biostatistics, and Occupational Health McGill University  Montreal QC Canada"},{"name":"Department of Medicine McGill University  Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/54.6.643"},{"issue":"3","key":"e_1_2_11_3_1","first-page":"401","article-title":"Tramadol extended\u2010release in the management of chronic pain","volume":"3","author":"McCarberg B","year":"2007","journal-title":"Ther Clin Risk Manag"},{"key":"e_1_2_11_4_1","unstructured":"AnekarAA CascellaM. 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