Losartan in hospitalized patients with COVID-19 in North America: An individual participant data meta-analysis.

Autor:	Di Stefano L; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD., Ram M; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.; Division of Brain Injury Outcomes, Johns Hopkins School of Medicine, Baltimore, MD., Scharfstein DO; Division of Biostatistics, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, UT., Li T; University of Colorado Denver, Anschutz Medical Campus, Denver, CO., Khanal P; Division of Brain Injury Outcomes, Johns Hopkins School of Medicine, Baltimore, MD., Baksh SN; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD., McBee N; Division of Brain Injury Outcomes, Johns Hopkins School of Medicine, Baltimore, MD., Bengtson CD; Department of Internal Medicine, University of Kansas Medical Center, KS City, KS., Gadomski A; Bassett Research Institute, Bassett Medical Center, Cooperstown, NY., Geriak M; Department of Research, Sharp Healthcare, San Diego, CA., Puskarich MA; Department of Emergency Medicine, University of Minnesota, Minneapolis, MN.; Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN., Salathe MA; Department of Internal Medicine, University of Kansas Medical Center, KS City, KS., Schutte AE; School of Population Health, University of New South Wales, The George Institute for Global Health, Sydney, NSW, Australia., Tignanelli CJ; Department of Surgery, University of Minnesota, Minneapolis, MN., Victory J; Bassett Research Institute, Bassett Medical Center, Cooperstown, NY., Bierer BE; Department of Medicine, Brigham and Women's Hospital, Boston, MA.; Harvard Medical School, Boston, MA., Hanley DF; Division of Brain Injury Outcomes, Johns Hopkins School of Medicine, Baltimore, MD., Freilich DA; Bassett Research Institute, Bassett Medical Center, Cooperstown, NY.; Department of Internal Medicine, Division of Infectious Diseases, Bassett Medical Center, Cooperstown, NY.
Jazyk:	angličtina
Zdroj:	Medicine [Medicine (Baltimore)] 2023 Jun 09; Vol. 102 (23), pp. e33904.
DOI:	10.1097/MD.0000000000033904
Abstrakt:	Background: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) have been hypothesized to benefit patients with COVID-19 via the inhibition of viral entry and other mechanisms. We conducted an individual participant data (IPD) meta-analysis assessing the effect of starting the ARB losartan in recently hospitalized COVID-19 patients. Methods: We searched ClinicalTrials.gov in January 2021 for U.S./Canada-based trials where an angiotensin-converting enzyme inhibitors/ARB was a treatment arm, targeted outcomes could be extrapolated, and data sharing was allowed. Our primary outcome was a 7-point COVID-19 ordinal score measured 13 to 16 days post-enrollment. We analyzed data by fitting multilevel Bayesian ordinal regression models and standardizing the resulting predictions. Results: 325 participants (156 losartan vs 169 control) from 4 studies contributed IPD. Three were randomized trials; one used non-randomized concurrent and historical controls. Baseline covariates were reasonably balanced for the randomized trials. All studies evaluated losartan. We found equivocal evidence of a difference in ordinal scores 13-16 days post-enrollment (model-standardized odds ratio [OR] 1.10, 95% credible interval [CrI] 0.76-1.71; adjusted OR 1.15, 95% CrI 0.15-3.59) and no compelling evidence of treatment effect heterogeneity among prespecified subgroups. Losartan had worse effects for those taking corticosteroids at baseline after adjusting for covariates (ratio of adjusted ORs 0.29, 95% CrI 0.08-0.99). Hypotension serious adverse event rates were numerically higher with losartan. Conclusions: In this IPD meta-analysis of hospitalized COVID-19 patients, we found no convincing evidence for the benefit of losartan versus control treatment, but a higher rate of hypotension adverse events with losartan. Competing Interests: S.N.B., N.M., and D.F.H. report receiving research funding from the Department of Defense for clinical trials of convalescent plasma for COVID-19 outside the submitted work. M.A.P. had money paid to his institution for COVID-19 trials from the Bill and Melinda Gates Foundation (trial of losartan), Minnesota Partnership for Biotechnology and Medical Genomics (trial of losartan), NHLBI NECTAR trial (trial of host response agents, including those targeting RAS), Parsemus Foundation (metformin trial), Rainwater Foundation (metformin, fluvoxamine, ivermectin trial), United Health Group (metformin, fluvoxamine, ivermectin trial), and for service as the independent medical safety monitor in the NHLBI Early Convalescent Plasma for High Risk Outpatients with COVID-19 clinical trial. Money was paid to him by the Protocol Development Committee (ACTIV-4d/ NECTAR), and he served without reimbursement on the REMAP CAP RAAS Domain Protocol Committee. A.E.S has received speaker honoraria and travel support from Servier, Sanofi, and Takeda. C.J.T. has received support from the Bill and Melinda Gates Foundation and Minnesota Partnership for Biotechnology and Medical Genomics (trial of losartan), and he received funding from Parsemus Foundation (metformin trial). The remaining authors have no conflicts of interest to disclose. (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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