A randomized trial supports the recommendation to continue treatment with ACEi or ARBs during hospitalization for COVID-19.
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ABSTRACT:
SUBMITTER: Volpe M
PROVIDER: S-EPMC7989525 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The COVID-19 pandemic has prompted an international effort to develop and repurpose medications and procedures to effectively combat the disease. Several groups have focused on the potential treatment utility of angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) for hypertensive COVID-19 patients, with inconclusive evidence thus far. We couple electronic medical record (EMR) and registry data of 3,643 patients from Spain, Italy, Germany, Ecuador, and the US with a machine learning framework to personalize the prescription of ACEIs and ARBs to hypertensive COVID-19 patients. Our approach leverages clinical and demographic information to identify hospitalized individuals whose probability of mortality or morbidity can decrease by prescribing this class of drugs. In particular, the algorithm proposes increasing ACEI/ARBs prescriptions for patients with cardiovascular disease and decreasing prescriptions for those with low oxygen saturation at admission. We show that personalized recommendations can improve patient outcomes by 1.0% compared to the standard of care when applied to external populations. We develop an interactive interface for our algorithm, providing physicians with an actionable tool to easily assess treatment alternatives and inform clinical decisions. This work offers the first personalized recommendation system to accurately evaluate the efficacy and risks of prescribing ACEIs and ARBs to hypertensive COVID-19 patients.
| S-EPMC7958102 | biostudies-literature
Project description:Purpose Due to the affinity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the human angiotensin converting enzyme 2 (ACE2) receptor, use of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) has been a major concern for clinicians during the 2020 pandemic. Meta-analyses have affirmed that these agents do not worsen clinical outcomes in SARS-CoV-2 infection. To date, only a limited number of studies have directly looked at the safety of inpatient prescription of ACEi/ARBs during acute COVID-19 illness. Methods A retrospective cohort analysis was conducted to investigate the impact of inpatient provision of ACEi/ARBs on morbidity and mortality in patients admitted to hospital with COVID-19. Relationships were explored using linear and logistic regression. Findings Six hundred and twelve adult patients met our inclusion criteria of which 151 (24.7%) patients were established on ACEi/ARBs. Despite correction for known confounders, discontinuation of ACEi/ARBs was highly predictive of worsened outcomes in COVID-19. The proportion of doses omitted in hospital was significantly associated with increased mortality (p<0.001, OR=9.59 [2.55-36.09]), maximum National Early Warning Score (NEWS-2; p<0.001, OR=1.66 [1.27-2.17]), maximum oxygen requirements (p<0.001, OR=3.00 [1.83-4.91]), and maximum C-Reactive Protein concentration (CRP; p=0.030, OR=1.83 [1.06-3.17]). Implications Our data demonstrates a strong association between missed ACEi/ARB doses with increased morbidity and mortality. The available evidence supports continuation of current accepted practice surrounding ACEi/ARB therapy in acute illness – which is to limit drug omission to established acute contraindications, to actively monitor such decisions and to restart therapy as soon as it is safe to do so.
| S-EPMC7906507 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with high incidence of multiorgan dysfunction and death. Angiotensin-converting enzyme 2 (ACE2), which facilitates SARS-CoV-2 host cell entry, may be impacted by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two commonly used antihypertensive classes. In a multicenter, international randomized controlled trial that began enrollment on March 31, 2020, participants are randomized to continuation vs withdrawal of their long-term outpatient ACEI or ARB upon hospitalization with COVID-19. The primary outcome is a hierarchical global rank score incorporating time to death, duration of mechanical ventilation, duration of renal replacement or vasopressor therapy, and multiorgan dysfunction severity. Approval for the study has been obtained from the Institutional Review Board of each participating institution, and all participants will provide informed consent. A data safety monitoring board has been assembled to provide independent oversight of the project.
| S-EPMC7722152 | biostudies-literature
Project description:Although some animal studies suggested that the use of ACEIs/ARBs could contribute for the prevention and treatment of the effects of the COVID-19 infection, there are also contradictory scenarios indicating that their use may exacerbate the deleterious conditions of the infection. As a result of the paradoxical issue of using ACEIs/ARBs during COVID-19, it is still an area requiring extended investigation to prove. Additionally, a trial evidence of their efficacy and the possible benefit risk analysis of these conventional drugs during COVID-19 in connection with other comorbidities like hypertension, heart failure, and renal disease associated with diabetes should also be addressed.
| S-EPMC7502385 | biostudies-literature
Project description:Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P < 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03-0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.
| S-EPMC8326462 | biostudies-literature
Project description:Background & aimsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV2)is a highly contagious virus that has infected 260 million individuals since December 2019. The severity of coronavirus disease 2019 (COVID-19) depends upon the complex interplay between viral factors and the host's inflammatory response, which can trigger a cascadeeventually leading to multiorgan failure. There is contradictory evidence that angiotensin-converting enzyme (ACEi) or angiotensin receptor blockers (ARBs) may affect mortality in patients with severe COVID-19, theoretically due to interaction with the bradykinin pathway. Therefore, we aim to explore the association between ACEi and ARB use and mortality in severe SARS-CoV2 infection.Severe acute respiratory yndrome with coronavirus (SARS-CoV2) is a highly contagious virus that has infected 260 million individuals since December 2019. The severity of COVID-19 depends upon the complex interplay between viral factors and the host's inflammatory response, which can trigger a cascadeeventually leading to multiorgan failure. There is contradictory evidence that angiotensin-converting enzyme (ACEi) or angiotensin receptor blockers (ARBs) may affect mortality in patients with severe COVID-19, theoretically due to interaction with the bradykinin pathway. Therefore, we aim to explore the association between ACEi and ARB use and mortality in severe SARS-CoV2 infection.Materials & methodologyThis multicenter retrospective observational study enrolled 2935 COVID-19 patients admitted at six hospitals in Southern California, USA, between March 2020 and August 2021. Our primary outcome was the association of pre-hospital use of ACEi and ARB on in-hospital mortality in COVID-19 patients. First, relevant deidentified patient data were extracted using an SQL program from the electronic medical record. Then, a bivariate analysis of the relationship between ACEi and ARB use and different study variables using χ2 and t test was done. Finally, we did a backward selection Cox multivariate regression analysis using mortality as a dependent variable.ResultsOf the 2935 patients in the study, hypertension was present in 40.6%, and congestive heart failure in 13.8%. ACEi and ARB were used by 17.5% and 11.3% of patients, respectively, with 28.8% of patients on either medication. After adjusting for confounding variables in the multivariate analysis, the use of ACEi (HR: 1.226, 95% CI: 0.989-1.520) or ARB (HR: 0.923, 95% CI: 0.701-1.216) was not independently associated with increased mortality.ConclusionOur results are consistent with the clinical guidelines and position statements per the International Society of Hypertension, that there is no indication to stop the use of ACEi/ARB in COVID-19 patients.
| S-EPMC9110920 | biostudies-literature
Project description:BackgroundThe clinical use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) in patients with COVID-19 infection remains controversial. Therefore, we performed a meta-analysis on the effects of ACEI/ARB on disease symptoms and laboratory tests in hypertensive patients infected with COVID-19 virus and those who did not use ACEI/ARB.MethodsWe systematically searched the relevant literatures from Pubmed, Embase, EuropePMC, CNKI, and other databases during the study period of 31 December 2019 (solstice, 15 March 2020), and analyzed the differences in symptoms and laboratory tests between patients with COVID-19 and hypertension who used ACEI/ARB drugs and those who did not. All statistical analyses were performed with REVMAN5.3.ResultsWe included a total of 1808 patients with hypertension diagnosed with COVID-19 in six studies. Analysis results show that ACEI/ARB drugs group D-dimer is lower (SMD = -0.22, 95%CI: -0.36 to -0.06), and the chances of getting fever is lower (OR = 0.74, 95%CI: 0.55 to 0.98). Meanwhile, laboratory data and symptoms were not statistical difference, but creatinine tends to rise (SMD = 0.22, 95% CI: 0.04 to 0.41).ConclusionWe found that the administration of ACEI/ARB drugs had positive effect on reducing D-dimer and the number of people with fever. Meanwhile it had no significant effect on other laboratory tests (creatinine excepted) or symptoms in patients with COVID-19, while special attention was still needed in patients with renal insufficiency.
| S-EPMC7747108 | biostudies-literature
Project description:BackgroundSARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin-angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19.MethodsACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUCSOFA), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596.FindingsBetween April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66-80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00-2·00) vs 1·00 (0·00-3·00); p=0·12). Discontinuation was associated with a significantly lower AUCSOFA (0·00 [0·00-9·25] vs 3·50 [0·00-23·50]; p=0·040), mean SOFA score (0·00 [0·00-0·31] vs 0·12 [0·00-0·78]; p=0·040), and 30-day SOFA score (0·00 [10-90th percentile, 0·00-1·20] vs 0·00 [0·00-24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group.InterpretationDiscontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options.FundingAustrian Science Fund and German Center for Cardiovascular Research.
| S-EPMC8195495 | biostudies-literature
Project description:The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1-angiotensin II-angiotensin AT1 receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2-angiotensin(1-7)-angiotensin AT2 receptor and the ACE-2-angiotensin(1-7)-Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.
| S-EPMC7198232 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19) has outbreak since early December 2019, and COVID-19 has caused over 100 million cases and 2 million deaths around the world. After one year of the COVID-19 outbreak, there is no certain and approve medicine against it. Drug repositioning has become one line of scientific research that is being pursued to develop an effective drug. However, due to the lack of COVID-19 data, there is still no specific drug repositioning targeting the COVID-19. In this paper, we propose a framework for COVID-19 drug repositioning. This framework has several advantages that can be exploited: one is that a local graph aggregating representation is used across a heterogeneous network to address the data sparsity problem; another is the multi-hop neighbors of the heterogeneous graph are aggregated to recall as many COVID-19 potential drugs as possible. Our experimental results show that our COVDR framework performs significantly better than baseline methods, and the docking simulation verifies that our three potential drugs have the ability to against COVID-19 disease.
| S-EPMC8458160 | biostudies-literature