IN-HOSPITAL CONTINUATION WITH ANGIOTENSIN RECEPTOR BLOCKERS IS ASSOCIATED WITH A LOWER MORTALITY RATE THAN CONTINUATION WITH ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN COVID-19 PATIENTS: A RETROSPECTIVE COHORT STUDY
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Abstract
Background
Several studies have reported a reduced risk of death associated with the inpatient use of angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) in COVID-19 patients, but have been criticized for incurring in several types of bias. Also, most studies have pooled ACEIs and ARBs as if they were a unique group, overlooking their pharmacological differences. We aimed to assess whether the in-hospital continuation of ARBs and ACEIs, in regular users of these drugs, was associated with a reduced risk of death as compared to their discontinuation and also to compare head-to-head ARBs with ACEIs.
Methods
Adult patients with a PCR-confirmed diagnosis of COVID-19 requiring admission during March, 2020 were consecutively selected from 7 hospitals in Madrid, Spain. Among them, we identified outpatient users of ACEIs/ARBs and divided them in two cohorts depending on treatment discontinuation/continuation at admission. Then, they were followed-up until discharge or in-hospital death. An intention-to-treat survival analysis was carried out and hazard ratios (HRs) and their 95%CI were computed through a Cox regression model adjusted for propensity scores of discontinuation and controlled by potential mediators.
Results
Out of 625 ACEI/ARB users, 340(54.4%) discontinued treatment. The in-hospital mortality rates were 27.6% and 27.7% in discontinuation and continuation cohorts, respectively (HR=1.01; 95%CI:0.70-1.46). No difference in mortality was observed between ARB and ACEI discontinuation (28.6% vs. 27.1%, respectively), while a significantly lower mortality rate was found among patients who continued with ARBs (20.8%,N=125) as compared to those who continued with ACEIs (33.1%,N=136; p=0.03). The head-to-head comparison (ARB vs. ACEI continuation) yielded an adjusted HR of 0.52 (95%CI:0.29-0.93), being especially notorious among males (HR=0.34; 95%CI:0.12-0.93), subjects older than 74 years (HR=0.46; 95%CI:0.25-0.85), and patients with obesity (HR=0.22; 95%CI:0.05-0.94), diabetes (HR=0.36; 95%CI:0.13-0.97) and heart failure (HR=0.12; 95%CI:0.03-0.97).
Conclusions
Among regular users of ARBs admitted for COVID-19, the in-hospital continuation with them was associated with an improved survival, while this was not observed with ACEIs. Regular users of ARBs should continue with this treatment if admitted for COVID-19, unless medically contraindicated. In admitted ACEI users, a switching to ARBs should be considered, especially among high-risk patients.
GRAPHICAL ABSTRACT
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SciScore for 10.1101/2021.02.01.21250853: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics approval: The present study was an extension of a previous study approved by the Ethics Research Committee of the University Hospital “Príncipe de Asturias” on March 18, 2020 (#SRAA-COVID19), including a waiver for the informed consent [6].
Consent: Ethics approval: The present study was an extension of a previous study approved by the Ethics Research Committee of the University Hospital “Príncipe de Asturias” on March 18, 2020 (#SRAA-COVID19), including a waiver for the informed consent [6].Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sente… SciScore for 10.1101/2021.02.01.21250853: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics approval: The present study was an extension of a previous study approved by the Ethics Research Committee of the University Hospital “Príncipe de Asturias” on March 18, 2020 (#SRAA-COVID19), including a waiver for the informed consent [6].
Consent: Ethics approval: The present study was an extension of a previous study approved by the Ethics Research Committee of the University Hospital “Príncipe de Asturias” on March 18, 2020 (#SRAA-COVID19), including a waiver for the informed consent [6].Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources All analyses were performed with STATA/SE v.15 (StataCorp LLC, College Station, TX. USA. 2017) and Python (Python Software Foundation, 2001-2020). STATA/SEsuggested: NoneStataCorpsuggested: (Stata, RRID:SCR_012763)Pythonsuggested: (IPython, RRID:SCR_001658)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has some limitations that must be discussed: 1) as in all observational studies, the possibility exists that there is some residual confounding due to unknown or unmeasured factors. Notwithstanding, it is important to remark that all our patients were users of RASIs prior to admission and were highly comparable at baseline, as shown by the good balance of covariates and the fact that the mean and median of the propensity scores for RASI discontinuation was close to 0.5 (not shown); indirectly, it is likely that unmeasured confounding variables are evenly distributed too, albeit this cannot be assured; as previously commented, this is specially applicable to the comparison of ACEI and ARB continuation cohorts; 2) the information on some severity biomarkers (i.e. interleukins 6 or 1β) were not routinely performed at that time and were not considered in the severity score built for this study; on this regard, we would like to emphasize that such score was created to reduce the number of covariates included in the PS models, and it is not proposed as a prognostic index (as we are quite aware that a specific and independent validation study would be necessary for that); 3) the study period selected (March, 2020) was the most critical of the first wave in Spain and, at that time, health professionals worked under an extraordinary pressure, which may have led to under-recording of some relevant clinical information; this limitation, however, does not apply to drugs as they...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04394117 Recruiting Controlled evaLuation of Angiotensin Receptor Blockers for C… NCT04312009 Recruiting Losartan for Patients With COVID-19 Requiring Hospitalizatio… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from scite Reference Check: We found no unreliable references.
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