Dataset Information

Outcomes Associated with the Use of Renin-Angiotensin-Aldosterone System Blockade in Hospitalized Patients with SARS-CoV-2 Infection.

ABSTRACT:

Background

Data regarding the benefits or harm associated with the continuation of Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Blockers (ARBs), especially the impact on inflammation, in hypertensive, hospitalized patients with COVID-19 in the United States is unclear.

Methods

This is a single-center cohort study of sequentially hospitalized patients with COVID-19 at Stony Brook University Medical Center from March 7, 2020 to April 1, 2020, inclusive of these dates. Data collection included history of known comorbidities, medications, vital signs and laboratory values (admission and during the hospitalization). Outcomes include inflammatory burden (composite scores for multiple markers of inflammation), acute kidney injury (AKI), admission to the intensive care unit (ICU), need for invasive mechanical ventilation, and mortality.

Results

Of the 300 patients in the study cohort, 80 patients (26.7%) had history of ACEI or ARB use prior to admission, with 61.3% (49/80) of these patients continuing the medications during hospitalization. Multivariable analysis revealed that the history of ACEI or ARB use prior to hospitalization was not associated with worse outcomes. In addition, the continuation of these agents during hospitalization was not associated with an increase in adverse outcomes and predicted fewer ICU admissions (OR=0.25, 0.08-0.81) with a decrease in the severity of inflammatory burden (peak CRP (6.9±3.1mg/dl, p=0.03) and peak inflammation score (2.3±1.1unit reduction, p=0.04)).

Conclusion

Use of ACEI or ARBs prior to hospitalization was not associated with adverse outcomes in COVID-19 and the therapeutic benefits of continuing ACEI or ARB in hospitalized patients with COVID-19 was not offset by adverse outcomes.

SUBMITTER: Chaudhri I

PROVIDER: S-EPMC7748256 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Outcomes Associated with the Use of Renin-Angiotensin-Aldosterone System Blockade in Hospitalized Patients with SARS-CoV-2 Infection.

Chaudhri Imran I Koraishy Farrukh M FM Bolotova Olena O Yoo Jeanwoo J Marcos Luis A LA Taub Erin E Sahib Haseena H Bloom Michelle M Ahmad Sahar S Skopicki Hal H Mallipattu Sandeep K SK

Kidney360 20200827 8

<h4>Background</h4>Data regarding the benefits or harm associated with the continuation of Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Blockers (ARBs), especially the impact on inflammation, in hypertensive, hospitalized patients with COVID-19 in the United States is unclear.<h4>Methods</h4>This is a single-center cohort study of sequentially hospitalized patients with COVID-19 at Stony Brook University Medical Center from March 7, 2020 to April 1, 2020, inclusiv ...[more]

PMID: 33345195

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Project description:Coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic with significant morbidity and mortality since first appearing in Wuhan, China, in late 2019. As many countries are grappling with the onset of their epidemics, pharmacotherapeutics remain lacking. The window of opportunity to mitigate downstream morbidity and mortality is narrow but remains open. The renin-angiotensin-aldosterone system (RAAS) is crucial to the homeostasis of both the cardiovascular and respiratory systems. Importantly, SARS-CoV-2 utilises and interrupts this pathway directly, which could be described as the renin-angiotensin-aldosterone-SARS-CoV (RAAS-SCoV) axis. There exists significant controversy and confusion surrounding how anti-hypertensive agents might function along this pathway. This review explores the current state of knowledge regarding the RAAS-SCoV axis (informed by prior studies of SARS-CoV), how this relates to our currently evolving pandemic, and how these insights might guide our next steps in an evidence-based manner. This review discusses the role of the RAAS-SCoV axis in acute lung injury and the effects, risks and benefits of pharmacological modification of this axis. There may be an opportunity to leverage the different aspects of RAAS inhibitors to mitigate indirect viral-induced lung injury. Concerns have been raised that such modulation might exacerbate the disease. While relevant preclinical, experimental models to date favour a protective effect of RAAS-SCoV axis inhibition on both lung injury and survival, clinical data related to the role of RAAS modulation in the setting of SARS-CoV-2 remain limited. Proposed interventions for SARS-CoV-2 predominantly focus on viral microbiology and aim to inhibit viral cellular injury. While these therapies are promising, immediate use may not be feasible, and the time window of their efficacy remains a major unanswered question. An alternative approach is the modulation of the specific downstream pathophysiological effects caused by the virus that lead to morbidity and mortality. We propose a preponderance of evidence that supports clinical equipoise regarding the efficacy of RAAS-based interventions, and the imminent need for a multisite randomised controlled clinical trial to evaluate the inhibition of the RAAS-SCoV axis on acute lung injury in COVID-19.

Project description:The novel severe acute respiratory syndrome (SARS) coronavirus SARS-CoV-2 walks the planet causing the rapid spread of the CoV disease 2019 (COVID-19) that has especially deleterious consequences for the patients with underlying cardiovascular diseases (CVDs). Entry of the SARS-CoV-2 into the host cell involves interaction of the virus (via the receptor-binding domain (RBD) of its spike glycoprotein) with the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) followed by the virus-ACE2 complex internalization by the cell. Since ACE2 is expressed in various tissues, such as brain, gut, heart, kidney, and lung, and since these organs represent obvious targets for the SARS-CoV-2 infection, therapeutic approaches were developed to either inhibit ACE2 or reduce its expression as a means of prevention of the virus entry into the corresponding host cells. The problem here is that in addition to be a receptor for the SARS-CoV-2 entry into the host cells, ACE2 acts as a key component of the renin-angiotensin-aldosterone system (RAAS) aimed at the generation of a cascade of vasoactive peptides coordinating several physiological processes. In RAAS, ACE2 degrades angiotensin II, which is a multifunctional CVD-promoting peptide hormone and converts it to a heptapeptide angiotensin-(1-7) acting as the angiotensin II antagonist. As protein multifunctionality is commonly associated with the presence of flexible or disordered regions, we analyze here the intrinsic disorder predisposition of major players related to the SARS-CoV-2 - RAAS axis. We show that all considered proteins contain intrinsically disordered regions that might have specific functions. Since intrinsic disorder might play a role in the functionality of query proteins and be related to the COVID-19 pathogenesis, this work represents an important disorder-based outlook of an interplay between the renin-angiotensin-aldosterone system and SARS-CoV-2. It also suggests that consideration of the intrinsic disorder phenomenon should be added to the modern arsenal of means for drug development.

Project description:BackgroundAngiotensin-converting-enzyme-2, being the receptor for SARS-CoV-2, is increased in the use of RAAS inhibitors. Therefore, concerns have been raised over risks of SARS-CoV-2 infection and poor prognosis of COVID-19 in persons with prior exposure to these drugs. This study aimed to systematically review available evidence for associations between exposure to RAAS inhibitors with susceptibility to SARS-CoV-2 infection and clinical outcomes in infected persons. It hopes to address the question on the effects of RAAS inhibitors on the risk of COVID-19 and its prognosis.Main bodySearch was conducted in the databases of PubMed, Scopus, Cochrane, Embase and MedRxiv.org from December 2019 to May 31, 2020, using relevant keywords. Additional articles were identified through hand-searching of reference lists. Studies that reported associations between positive tests to COVID-19 and use of RAAS inhibitors, and treatment outcomes of COVID-19 patients who had exposure to RAAS inhibitors were considered eligible. The Newcastle-Ottawa scale was used to assess risk of bias in individual studies. The review was conducted in line with Preferred Regulatory Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 2009. From the 952 studies screened and 2 studies from reference hand-searching, 18 were reviewed. Four studies evaluated the risks for SARS-CoV-2 infection among RAAS inhibitors users, and 16 (including 2 of the 4 studies) evaluated the clinical outcomes associated with previous exposure to RAAS inhibitors.ConclusionEvidence does not suggest higher risks for SARS-CoV-2 infection or poor disease prognosis in the use of RAAS inhibitors. This suggests the continued use of RAAS inhibitors by patients with existing needs, which supports the position statements of American Heart Association and European societies for Cardiology.Supplementary informationThe online version contains supplementary material available at 10.1186/s43094-021-00224-4.

Project description:AimThe role of cardiovascular (CV) pharmacotherapies in patients with severe COVID-19 pneumonia remains controversial. This study aims to assess the impact of renin-angiotensin system modulation (RASi) (either angiotensin-converting enzymes (ACEIs) or angiotensin-receptor blockers (ARBs)) on COVID-19 outcome.MethodsWe performed a cohort study on consecutive patients admitted for COVID-19 pneumonia at the Internal Medicine Unit of Sant'Orsola-Malpighi Hospital in Bologna, Italy. Patients with a possible alternative cause of respiratory failure other than COVID-19 were excluded. Clinical, pharmacological and laboratory data at admission and during the hospitalization were collected. Patients were treated with intravenous dexamethasone, low molecular weight heparin and nasal flow or Venturi mask oxygen. Subjects were followed until discharge, Intensive Care Unit (ICU) admission or death. Severe cases were defined by acute respiratory distress syndrome (arterial oxygen partial pressure and the fraction of inhaled oxygen ratio (P/F) ≤ 100 mmHg/%, or P/F ≤ 150 mmHg/% and respiratory rate ≥ 26/min). Patients with chronic use of RAS modulation were compared with those without for the composite outcome of in-hospital mortality or ICU admission. Hazard ratios (HR) were obtained by Cox regression, adjusted for several clinical factors.ResultsOf the 268 patients enrolled in the study, 93 (35%, mean age 68 ± 13 years, 67% males) were treated with RASi (58% ACEIs and 42% ARBs). There were no meaningful differences between the RASI and no RASI group regarding clinical and laboratory parameters at admission. As expected, patients in the RASi group had a higher prevalence of hypertension, diabetes mellitus, atrial fibrillation, and ischemic heart disease. One hundred eight patients (40%) were admitted to ICU during hospitalization due to severe respiratory failure, and 24 (9%) died. The risk of in-hospital death or ICU admission was lower in the RASI group than in the non-RASI group (age and sex-adjusted HR 0.57, 95% CI 0.37-0.8), even after adjustment for several comorbidities (fully adjusted HR 0.44, 95% CI 0.26-0.74). Seven (7.5%) patients died in the RASi group vs 17 (9.7%) in the non-RASi group, leading to a non-statistically significant mortality risk reduction (fully adjusted HR 0.69, 95% CI 0.18-1.90). The lower risk in the RASi group was primarily related to ARBs use compared to ACEIs (HR 0.5, 95% CI 0.28-0.92 and HR 0.82, 95% CI 0.51-1.32, respectively).ConclusionsOur study showed an inverse association between the chronic use of RASi and COVID-19 pneumonia severity (either ICU admissions or in-hospital death), even when significant comorbidities are considered.

Project description:BackgroundClinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blocker therapy. However, evidence is lacking about whether follow-up testing reduces therapy-related adverse outcomes.Methods and resultsWe conducted 2 population-based retrospective cohort studies in Kaiser Permanente Northern California and Ontario, Canada. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACE inhibitor or angiotensin II receptor blocker therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression. We also developed and externally validated a risk score to identify patients at risk of having abnormally high serum creatinine and potassium values in follow-up. We identified 75 251 matched pairs initiating ACE inhibitor or angiotensin II receptor blocker therapy between January 1, 2007, and December 31, 2017, in Kaiser Permanente Northern California. Follow-up testing was not significantly associated with 30-day all-cause mortality in Kaiser Permanente Northern California (hazard ratio, 0.75 [95% CI, 0.54-1.06]) and was associated with higher mortality in 84 905 matched pairs in Ontario (hazard ratio, 1.32 [95% CI, 1.07-1.62]). In Kaiser Permanente Northern California, follow-up testing was significantly associated with higher rates of hospitalization with acute kidney injury (hazard ratio, 1.66 [95% CI, 1.10-2.22]) and hyperkalemia (hazard ratio, 3.36 [95% CI, 1.08-10.41]), as was observed in Ontario. The risk score for abnormal potassium provided good discrimination (area under the curve [AUC], 0.75) and excellent calibration of predicted risks, while the risk score for abnormal serum creatinine provided moderate discrimination (AUC, 0.62) but excellent calibration.ConclusionsRoutine laboratory monitoring after ACE inhibitor or angiotensin II receptor blocker initiation was not associated with a lower risk of 30-day mortality. We identified patient subgroups in which targeted testing may be effective in identifying therapy-related changes in serum potassium or kidney function.

Dataset Information

Outcomes Associated with the Use of Renin-Angiotensin-Aldosterone System Blockade in Hospitalized Patients with SARS-CoV-2 Infection.

Background

Methods

Results

Conclusion

Publications

Outcomes Associated with the Use of Renin-Angiotensin-Aldosterone System Blockade in Hospitalized Patients with SARS-CoV-2 Infection.

Similar Datasets

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