Effect of P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial.

Autor:	Berger JS; Center for the Prevention of Cardiovascular Disease, NYU Grossman School of Medicine, New York, New York., Neal MD; Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania., Kornblith LZ; Department of Surgery, University of California, San Francisco, San Francisco.; Department of Laboratory Medicine, University of California, San Francisco, San Francisco., Gong MN; Albert Einstein College of Medicine, Bronx, New York., Reynolds HR; Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York., Cushman M; University of Vermont College of Medicine, Burlington., Althouse AD; Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.; Now with Medtronic, Minneapolis, Minnesota., Lawler PR; Peter Munk Cardiac Centre, Toronto, Ontario, Canada., McVerry BJ; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania., Kim KS; College of Pharmacy, University of Illinois at Chicago, Chicago., Baumann Kreuziger L; Versity Blood Research Institute, Milwaukee, Wisconsin., Solomon SD; Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., Kosiborod MN; Saint Luke's Mid America Heart Institute, University of Missouri, Kansas City., Berry SM; Berry Consultants, LLC, Austin, Texas., Bochicchio GV; Washington University School of Medicine, St Louis, Missouri., Contoli M; Department of Translational Medicine, Università di Ferrara, Ferrara, Italy., Farkouh ME; Peter Munk Cardiac Centre, Toronto, Ontario, Canada., Froess JD; Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania., Gandotra S; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama, Birmingham., Greenstein Y; Rutgers New Jersey Medical School, Newark., Hade EM; Division of Biostatistics, Department of Population Health, NYU Grossman School of Medicine, New York, New York., Hanna N; Ascension St John Clinical Research Institute, Tulsa, Oklahoma., Hudock K; University of Cincinnati Medical Center, Cincinnati, Ohio., Hyzy RC; Division of Pulmonary and Critical Care, Department of Medicine, University of Michigan, Ann Arbor., Ibáñez Estéllez F; Hospital Emergencias Enfermera Isabel Zendal, Madrid, Spain., Iovine N; Division of Infectious Diseases and Global Medicine, Department of Medicine, University of Florida, Gainesville., Khanna AK; Perioperative Outcomes and Informatics Collaborative, Wake Forest University School of Medicine, Winston-Salem, North Carolina.; Outcomes Research Consortium, Cleveland, Ohio., Khatri P; University of Cincinnati Medical Center, Cincinnati, Ohio., Kirwan BA; Socar Research SA, Nyon, Switzerland., Kutcher ME; University of Mississippi Medical Center, Jackson., Leifer E; National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland., Lim G; Ronald Reagan UCLA Medical Center, Los Angeles, California., Lopes RD; Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham., Lopez-Sendon JL; IdiPaz Research Institute, Hospital Universitario La Paz, Madrid, Spain., Luther JF; Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania., Nigro Maia L; Fundação Faculdade Regional De Medicina De São José Do Rio Preto, São José do Rio Preto, Brazil., Quigley JG; Division of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago., Wahid L; Division of Internal Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina., Wilson JG; Stanford University Medical Center, Stanford, California., Zarychanski R; Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada., Kindzelski A; National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland., Geraci MW; Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania., Hochman JS; Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2023 May 01; Vol. 6 (5), pp. e2314428. Date of Electronic Publication: 2023 May 01.
DOI:	10.1001/jamanetworkopen.2023.14428
Abstrakt:	Importance: Platelet activation is a potential therapeutic target in patients with COVID-19. Objective: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients. Intervention: Participants were randomly assigned to receive a P2Y12 inhibitor or no P2Y12 inhibitor (usual care) for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death and, for participants who survived to hospital discharge, the number of days free of cardiovascular or respiratory organ support up to day 21 of the index hospitalization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis. Results: At the time of trial termination, 949 participants (median [IQR] age, 56 [46-65] years; 603 male [63.5%]) had been randomly assigned, 479 to the P2Y12 inhibitor group and 470 to usual care. In the P2Y12 inhibitor group, ticagrelor was used in 372 participants (78.8%) and clopidogrel in 100 participants (21.2%). The estimated adjusted odds ratio (AOR) for the effect of P2Y12 inhibitor on organ support-free days was 1.07 (95% credible interval, 0.85-1.33). The posterior probability of superiority (defined as an OR > 1.0) was 72.9%. Overall, 354 participants (74.5%) in the P2Y12 inhibitor group and 339 participants (72.4%) in the usual care group survived to hospital discharge (median AOR, 1.15; 95% credible interval, 0.84-1.55; posterior probability of superiority, 80.8%). Major bleeding occurred in 13 participants (2.7%) in the P2Y12 inhibitor group and 13 (2.8%) in the usual care group. The estimated mortality rate at 90 days for the P2Y12 inhibitor group was 25.5% and for the usual care group was 27.0% (adjusted hazard ratio, 0.96; 95% CI, 0.76-1.23; P = .77). Conclusions and Relevance: In this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.
Databáze:	MEDLINE
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