Abstract :
Abstract Background Morphine is commonly used to relieve pain, anxiety and dyspnea in STEMI but it lowers blood pressure and delays the activity of oral antiplatelet agents. The impact of morphine on clinical outcomes remains unknown. This analysis was performed to determine if morphine use was associated with increased risk of adverse clinical events among STEMI patients treated with fibrinolytic therapy and clopidogrel or ticagrelor. Methods In the Ticagrelor in Patients with ST Elevation Myocardial Infarction Treated with Pharmacological Thrombolysis (TREAT) study, 3799 STEMI patients treated with fibrinolysis were randomized to receive clopidogrel or ticagrelor. Morphine use was left to the discretion of the treating physicians. In this pre-specified analysis, we evaluated clinical outcomes based on the use and timing of morphine administration. Outcomes were stratified by randomized treatment group. Multivariable analysis was performed using Inverse Probability Treatment Weighting (IPTW) weighting. Results Morphine was used in 53% of patients. After adjustment using IPTW weighting, morphine use was associated with higher hazard of reinfarction at 7 days (HR 4.9, P = .0006) and 30 days (HR 1.7, P = .04), and lower hazard of major bleeding (HR 0.37, P = .006). There was no significant difference in mortality at any time point. Conclusions Among patients with STEMI treated with fibrinolytic therapy, morphine use was associated with a higher risk of early reinfarction and a lower risk of major bleeding but no difference in mortality. Clinical trial registration clinicaltrials.gov Identifier: NCT02298088. Author Affiliation: (a) Department of Medicine, Southlake Regional Health Centre, University of Toronto, 581 Davis Drive, Newmarket, Toronto, Ontario L3Y 2P6, Canada (b) Department of Medicine, Canadian Heart Research Centre, Toronto, Ontario, Canada (c) Clinical Operations, Research Institute, Heart Hospital (HCor), São Paulo, Brazil (d) Department of Medicine, London Health Sciences Centre, Western University, London, Ontario, Canada (e) Department of Medicine, Cardiovascular Services, Auckland City Hospital, Auckland, New Zealand (f) Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil (g) Department of Medicine, Prairie Vascular Research Network and Saskatchewan Health Authority, University of Saskatchewan, Regina, Saskatchewan, Canada (h) Department of Medicine, Hospital de Alta Complejidad El Cruce, Buenos Aires, Argentina (i) Department of Medicine, Duke Clinical Research Institute, Durham, NC, United States (j) Department of Medicine, Universidade Federal de São Paulo, São Paulo, Brazil (k) Department of Medicine, Monash Cardiovascular Research Centre, Monash University, Melbourne, Victoria, Australia (l) Department of Medicine, Emergency Cardiology Department, Institute of Cardiology, Kiev, Ukraine (m) Department of Medicine, Pirogov Russian National Research Medical University, Moscow, Russia (n) Department of Medicine, CK Hui Heart Centre, Edmonton, Alberta, Canada (o) Department of Medicine, New Brunswick Heart Centre, Dalhousie University, Halifax, Nova Scotia, Canada (p) Department of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru (q) Department of Medicine, Heart Hospital (HCor), São Paulo, Brazil (r) Department of Medicine, Canadian Heart Research Centre (CHRC) and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (s) Academic Research Organization (ARO), Hospital Israelita Albert Einstein, Sao Paulo, SP, Brazil * Corresponding author. Article History: Received 31 August 2021; Accepted 3 May 2022 (footnote)1 In his role as the Medical Co-Director of the New Brunswick Heart Centre Research Initiative and CardioVascular Research New Brunswick, Dr. Sohrab Lutchmedial developed and led the cardiology research infrastructure at his center for almost 20 years, providing opportunities for patients to participate in clinical research and making important provincial and national contributions to the care of those with, and at risk for, cardiovascular disease. Byline: Warren J. Cantor, MD [cantorw@rogers.com] (a,*), Mary Tan, MSC (b), Otavio Berwanger, MD, PHD (s), Shahar Lavi, MD (d), Harvey D. White, MD, DSC (e), Jose C. Nicolau, MD, PHD (f), Payam Dehghani, MD (g), Carlos D. Tajer, MD, PHD (h), Renato D. Lopes, MD, MHS, PHD (i,j), Diogo D.F. Moia, PHARMD (c), Stephen J. Nicholls, MD, PHD (k), Alexander Parkhomenko, MD, PHD (l), Oleg Averkov, MD, PHD (m), Neil Brass, MD (n), Sohrab Lutchmedial, MDCM (o,1), Germán Malaga, MD (p), Lucas P. Damiani, MSC (c), Leopoldo S. Piegas, MD, PHD (q), Christopher B. Granger, MD, PHD (i), Shaun G. Goodman, MD, MSC (r)