{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T20:32:05Z","timestamp":1774557125904,"version":"3.50.1"},"reference-count":48,"publisher":"BMJ","issue":"3","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2019,1,23]]},"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Morphine is frequently used in acute coronary syndrome (ACS) due to its analgesic effect, it being recommended in the main cardiology guidelines in Europe and the USA. However, controversy exists regarding its routine use due to potential safety concerns. We conducted a systematic review of randomised-controlled trials (RCTs) and observational studies to synthesise the available evidence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Systematic review and meta-analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Data sources<\/jats:title>\n                  <jats:p>CENTRAL, MEDLINE, EMBASE and trial registries.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Eligibility criteria for selecting studies<\/jats:title>\n                  <jats:p>We included RCTs and observational studies evaluating the impact of morphine in cardiovascular outcomes or platelet reactivity measures.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Data extraction and synthesis<\/jats:title>\n                  <jats:p>Data were screened, extracted and appraised by two independent reviewers. The data were pooled results using a random-effects model. Outcomes included in-hospital mortality, major adverse cardiovascular events (MACE), platelet reactivity (using VerifyNow) and bleeding, reported as relative risk (RR) with 95%\u2009CI. We assessed the confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We followed the Meta-analysis Of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Five RCTs and 12 observational studies were included, enrolling 69\u2009993 participants. Pooled results showed an increased risk of in-hospital mortality (RR 1.45 [95% CI 1.10 to 1.91], low GRADE confidence), MACE (RR 1.21, 95%\u2009CI 1.02 to 1.45) and an increased platelet reactivity at 1 and 2\u2009hours (59.37 platelet reactivity units [PRU], 95%\u2009CI 36.04 to 82.71; 68.28 PRU, 95%\u2009CI 37.01 to 99.55, high GRADE confidence) associated with morphine. We found no significant difference in the risk of bleeding. We found no differences in subgroup analyses based on study design and ACS subtype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Morphine was associated with an increased risk of in-hospital mortality and MACE but the high risk of bias leads to low result confidence. There is high confidence that morphine decreases the antiplatelet effect of P2Y12 inhibitors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PROSPERO registration number<\/jats:title>\n                  <jats:p>CRD42016036357.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2018-025232","type":"journal-article","created":{"date-parts":[[2019,3,16]],"date-time":"2019-03-16T05:30:13Z","timestamp":1552714213000},"page":"e025232","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Morphine in acute coronary syndrome: systematic review and meta-analysis"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7802-1897","authenticated-orcid":false,"given":"Gon\u00e7alo Silva","family":"Duarte","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2836-9497","authenticated-orcid":false,"given":"Afonso","family":"Nunes-Ferreira","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Cardiologia, Hospital Universit\u00e1rio de Santa Maria (CHLN), CAML, Centro Cardiovascular da Universidade de Lisboa - CCUL, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"}]},{"given":"Filipe Brogueira","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular, Lisboa, Portugal"}]},{"given":"Fausto J","family":"Pinto","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Cardiologia, Hospital Universit\u00e1rio de Santa Maria (CHLN), CAML, Centro Cardiovascular da Universidade de Lisboa - CCUL, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-5113","authenticated-orcid":false,"given":"Joaquim J","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Campus Neurol\u00f3gico S\u00e9nior, Torres Vedras, Portugal"},{"name":"Laboratory of Clinical Pharmacology and Therapeutics, Universidade de Lisboa Faculdade de Medicina, Lisboa, Portugal"}]},{"given":"Joao","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Therapeutics, Universidade de Lisboa Faculdade de Medicina, Lisboa, Portugal"},{"name":"Centro de Estudos de Medicina Baseada na Evidencia, Universidade de Lisboa, Lisboa, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-5673","authenticated-orcid":false,"given":"Daniel","family":"Caldeira","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"},{"name":"Instituto de Medicina Molecular, Lisboa, Portugal"},{"name":"Servi\u00e7o de Cardiologia, Hospital Universit\u00e1rio de Santa Maria (CHLN), CAML, Centro Cardiovascular da Universidade de Lisboa - CCUL, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"}]}],"member":"239","published-online":{"date-parts":[[2019,3,15]]},"reference":[{"key":"2025101813163070000_9.3.e025232.1","unstructured":"Organization. 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