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:We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.
| S-EPMC9579198 | 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:ObjectivesCaring Contacts are an emerging intervention that aims to reduce distress and suicide risk after acute psychiatric care. This trial aimed to determine whether, during a pandemic, there was any evidence that the mental health benefits and reduction in suicidal ideation (SI) associated with delivering Caring Contacts to recently discharged psychiatric patients were greater than a control communication. The secondary objective was to identify whether the predicted benefits were greater among people living alone or those diagnosed with depression.MethodA single-site pilot randomized clinical trial (n = 100), with patients recruited from the adult Inpatient Psychiatry Unit at Sunnybrook Health Sciences Centre, Toronto, Canada between August 2020 and May 2021. Participants were randomized (1:1) to the Caring Contact or control group. Participants received three Caring Contact or control communications via email or mail (on days 4, 21, and 56 post-discharge). Mental health symptoms were assessed using the self-report Hopkins Symptom Checklist-25 (HSCL-25) scores at discharge (baseline) and when participants received each communication. Analysis of variance was used for the primary comparisons and exploratory analyses for subgroups.ResultsBoth groups experienced a significant worsening of mental health symptoms at all time points post-discharge relative to baseline. There were no significant differences between groups at any time point, however, on day 4 there was a 24.2% and 72.6% attenuated worsening in the Caring Contact group compared to the control group for total symptom severity and SI, respectively. There was no significant interaction effect for the depression subgroup or those living alone.ConclusionsWhile this pilot study was not powered to identify significant differences between groups, results are indicative of feasibility and acceptability of the intervention and provide some indication that Caring Contacts may have benefited patients in the days following discharge, supporting the need for larger-scale trials. The study was registered with clinicaltrials.gov (study ID NCT04456062).
| S-EPMC9412148 | biostudies-literature
Project description:BackgroundCOVID-19 (coronavirus disease 2019) is associated with heightened risks of venous and arterial thrombosis and hospitalization due to respiratory failure. To assess whether prophylactic anticoagulation can safely reduce the frequency of venous and arterial thrombosis, hospitalization, and death in nonhospitalized patients with symptomatic COVID-19 and at least one thrombosis risk factor, we conducted the PREVENT-HD double-blind, placebo-controlled randomized trial (A Study of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic COVID-19] Infection).MethodsPREVENT-HD was conducted between August 2020 and April 2022 at 14 US integrated health care delivery networks. A virtual trial design used remote informed consent and clinical monitoring and facilitated data collection through electronic health record integration with a cloud-based research platform. Nonhospitalized patients with symptomatic COVID-19 and at least one thrombosis risk factor were enrolled and randomly assigned to either 10 mg of oral rivaroxaban or placebo daily for 35 days. The primary efficacy outcome was time to first occurrence of a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic arterial embolism, hospitalization, or death through day 35. The principal safety end point was International Society on Thrombosis and Hemostasis critical-site or fatal bleeding. The last study visit was on day 49.ResultsThe study was terminated prematurely because of enrollment challenges and a lower-than-expected blinded pooled event rate. A total of 1284 patients underwent randomization with complete accrual of primary events through May 2022. No patients were lost to follow-up. The primary efficacy outcome occurred in 22 of 641 in the rivaroxaban group and 19 of 643 in the placebo group (3.4% versus 3.0%; hazard ratio, 1.16 [95% CI, 0.63-2.15]; P=0.63). No patient in either group experienced critical-site or fatal bleeding. One patient receiving rivaroxaban had a major bleed.ConclusionsThe study was terminated prematurely after enrollment of 32% of planned accrual because of recruitment challenges and lower-than-expected event rate. Rivaroxaban prescribed for 35 days in nonhospitalized patients with symptomatic COVID-19 at risk for thrombosis did not appear to reduce a composite end point of venous and arterial thrombotic events, hospitalization, and death.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT04508023.
| S-EPMC10270282 | biostudies-literature
Project description:BackgroundPre-eclampsia and eclampsia are among the major threats to pregnant women and fetuses, but they can be mitigated by prevention and early screening. Existing observational research presents conflicting evidence regarding the causal effects of coronavirus disease 2019 (COVID-19) on pre-eclampsia risk. Through Mendelian randomization (MR), this study aims to investigate the causal effect of three COVID-19 severity phenotypes on the risk of pre-eclampsia and eclampsia to provide more rigorous evidence.MethodsTwo-sample MR was utilized to examine causal effects. Summary-level data from genome-wide association studies (GWAS) of individuals of European ancestry were acquired from the GWAS catalog and FinnGen databases. Single-nucleotide polymorphisms associated with COVID-19 traits at p < 5 × -8 were obtained and pruned for linkage disequilibrium to generate instrumental variables for COVID-19. Inverse variance weighted estimates were used as the primary MR results, with weighted median and MR-Egger as auxiliary analyses. The robustness of the MR findings was also evaluated through sensitivity analyses. Bonferroni correction was applied to primary results, with a p < 0.0083 considered significant evidence and a p within 0.083-0.05 considered suggestive evidence.ResultsCritical ill COVID-19 [defined as hospitalization for COVID-19 with either a death outcome or respiratory support, OR (95% CI): 1.17 (1.03-1.33), p = 0.020] and hospitalized COVID-19 [defined as hospitalization for COVID-19, OR (95% CI): 1.10 (1.01-1.19), p = 0.026] demonstrated suggestive causal effects on pre-eclampsia, while general severe acute respiratory syndrome coronavirus 2 infection did not exhibit a significant causal effect on pre-eclampsia. None of the three COVID-19 severity phenotypes exhibited a significant causal effect on eclampsia.ConclusionsOur investigation demonstrates a suggestive causal effect of genetic susceptibility to critical ill COVID-19 and hospitalized COVID-19 on pre-eclampsia. The COVID-19 severity exhibited a suggestive positive dose-response relationship with the risk of pre-eclampsia. Augmented attention should be paid to pregnant women hospitalized for COVID-19, especially those needing respiratory support.
| S-EPMC10957568 | 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