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      Clinical Characteristics and Implications of Bradycardia in COVID-19 Patients Treated with Remdesivir: A Single-Center Retrospective Cohort Study

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          Abstract

          Background and Objectives

          Remdesivir is an antiviral drug used to treat coronavirus disease 2019 (COVID-19) with a relatively obscure cardiac effect profile. Previous studies have reported bradycardia associated with remdesivir, but few have examined its clinical characteristics. The objective of this study was to investigate remdesivir associated bradycardia and its associated clinical characteristics and outcomes.

          Methods

          This is a single-institution retrospective study that investigated bradycardia in 600 patients who received remdesivir for treatment of COVID-19. A total of 375 patients were included in the study after screening for other known causes of bradycardia (atrioventricular [AV] nodal blockers). All patients were analyzed for episodes of bradycardia from when remdesivir was initiated up to 5 days after completion, a time frame based on the drug’s putative elimination half-life. Univariate and multivariate statistical tests were conducted to analyze the data.

          Results

          The mean age of the sample was 56.63 ± 13.23 years. Of patients who met inclusion criteria, 49% were found to have bradycardia within 5 days of remdesivir administration. Compared to the cohort without a documented bradycardic episode, patients with bradycardia were significantly more likely to experience inpatient mortality (22% vs 12%, p = 0.01). The patients with bradycardia were found to have marginally higher serum D-dimer levels (5.2 vs 3.4 µg/mL, p = 0.05) and were more likely to undergo endotracheal intubation (28% vs 14%, p = 0.008). Male sex, hyperlipidemia, and bradycardia within 5 days of completing remdesivir were significant predictors of inpatient mortality. No significant differences in length of stay were found.

          Conclusions

          Bradycardia that occurs during or shortly after remdesivir treatment in COVID-19 patients may be associated with an increased rate of in-hospital mortality. However, COVID-19 and its cardiac complications cannot be excluded as potential contributors of bradycardia in the present study. Future studies are needed to further delineate the cardiac characteristics of COVID-19 and remdesivir.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40261-022-01187-x.

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          Most cited references67

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          G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences

          G*Power (Erdfelder, Faul, & Buchner, 1996) was designed as a general stand-alone power analysis program for statistical tests commonly used in social and behavioral research. G*Power 3 is a major extension of, and improvement over, the previous versions. It runs on widely used computer platforms (i.e., Windows XP, Windows Vista, and Mac OS X 10.4) and covers many different statistical tests of the t, F, and chi2 test families. In addition, it includes power analyses for z tests and some exact tests. G*Power 3 provides improved effect size calculators and graphic options, supports both distribution-based and design-based input modes, and offers all types of power analyses in which users might be interested. Like its predecessors, G*Power 3 is free.
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            Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses.

            G*Power is a free power analysis program for a variety of statistical tests. We present extensions and improvements of the version introduced by Faul, Erdfelder, Lang, and Buchner (2007) in the domain of correlation and regression analyses. In the new version, we have added procedures to analyze the power of tests based on (1) single-sample tetrachoric correlations, (2) comparisons of dependent correlations, (3) bivariate linear regression, (4) multiple linear regression based on the random predictor model, (5) logistic regression, and (6) Poisson regression. We describe these new features and provide a brief introduction to their scope and handling.
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              Remdesivir for the Treatment of Covid-19 — Final Report

              Abstract Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. Results A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). Conclusions Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)
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                Author and article information

                Contributors
                Ariyon.Schreiber@unlv.edu
                Journal
                Clin Drug Investig
                Clin Drug Investig
                Clinical Drug Investigation
                Springer International Publishing (Cham )
                1173-2563
                1179-1918
                17 August 2022
                : 1-12
                Affiliations
                [1 ]GRID grid.272362.0, ISNI 0000 0001 0806 6926, Department of Internal Medicine, , Kirk Kerkorian School of Medicine at the University of Nevada Las Vegas (UNLV), ; 2040 W. Charleston Blvd., Mail Stop: 3070, Las Vegas, NV 89102-2244 USA
                [2 ]GRID grid.272362.0, ISNI 0000 0001 0806 6926, Department of Medicine, , Kirk Kerkorian School of Medicine at UNLV, ; Las Vegas, Nevada USA
                [3 ]GRID grid.272362.0, ISNI 0000 0001 0806 6926, Department of Medical Education & Office of Research, , Kirk Kerkorian School of Medicine at UNLV, ; Las Vegas, Nevada USA
                [4 ]GRID grid.272362.0, ISNI 0000 0001 0806 6926, Department of Cardiology, , Kirk Kerkorian School of Medicine at UNLV, ; Las Vegas, Nevada USA
                Author information
                http://orcid.org/0000-0003-2947-1095
                http://orcid.org/0000-0002-0958-4343
                http://orcid.org/0000-0002-0722-0191
                http://orcid.org/0000-0001-7153-0736
                http://orcid.org/0000-0003-0915-2011
                http://orcid.org/0000-0001-6294-5390
                http://orcid.org/0000-0001-9949-7333
                http://orcid.org/0000-0003-3133-6028
                http://orcid.org/0000-0001-5269-8488
                Article
                1187
                10.1007/s40261-022-01187-x
                9385079
                35978159
                5d0c1c2c-0a40-4c19-ba2e-bf03c624d8a8
                © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 26 July 2022
                Categories
                Original Research Article

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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