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2.
Circulation ; 141(20): 1648-1655, 2020 May 19.
Article in English | MEDLINE | ID: covidwho-2138307

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.


Subject(s)
Betacoronavirus , Cardiovascular Diseases , Coronavirus Infections , Pandemics , Peptidyl-Dipeptidase A , Pneumonia, Viral , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 , Cardiovascular Diseases/complications , Cardiovascular Diseases/enzymology , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/enzymology , Coronavirus Infections/therapy , Coronavirus Infections/virology , Humans , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/complications , Pneumonia, Viral/enzymology , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Receptors, Virus/antagonists & inhibitors , Receptors, Virus/metabolism , SARS-CoV-2
3.
BMJ ; 379: e072175, 2022 11 16.
Article in English | MEDLINE | ID: covidwho-2117032

ABSTRACT

OBJECTIVE: To determine whether disrupting the renin angiotensin system with angiotensin receptor blockers will improve clinical outcomes in people with covid-19. DESIGN: CLARITY was a pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. SETTING: 17 hospital sites in India and Australia. PARTICIPANTS: Participants were at least 18 years old, previously untreated with angiotensin receptor blockers, with a laboratory confirmed diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who had been admitted to hospital for management of covid-19. INTERVENTION: Oral angiotensin receptor blockers (telmisartan in India) or placebo (1:1) for 28 days. MAIN OUTCOME MEASURES: The primary endpoint was covid-19 disease severity using a modified World Health Organization Clinical Progression Scale (WHO scale) at day 14. Secondary outcomes were WHO scale scores at day 28, mortality, intensive care unit admission, and respiratory failure. Analyses were evaluated on an ordinal scale in the intention-to-treat population. RESULTS: Between 3 May 2020 and 13 November 2021, 2930 people were screened for eligibility, with 393 randomly assigned to angiotensin receptor blockers (of which 388 (98.7%) to telmisartan 40 mg/day) and 394 to the control group. 787 participants were randomised: 778 (98.9%) from India and nine (1.1%) from Australia. The median WHO scale score at day 14 was 1 (interquartile range 1-1) in 384 participants assigned angiotensin receptor blockers and 1 (1-1) in 382 participants assigned placebo (adjusted odds ratio 1.51 (95% credible interval 1.02 to 2.23), probability of an odds ratio of >1 (Pr(OR>1)=0.98). WHO scale scores at day 28 showed little evidence of difference between groups (1.02 (0.55 to 1.87), Pr(OR>1)=0.53). The trial was stopped when a prespecified futility rule was met. CONCLUSIONS: In patients admitted to hospital for covid-19, mostly with mild disease, not requiring oxygen, no evidence of benefit, based on disease severity score, was found for treatment with angiotensin receptor blockers, using predominantly 40 mg/day of telmisartan. TRIAL REGISTRATION: ClinicalTrials.gov NCT04394117.


Subject(s)
Angiotensin Receptor Antagonists , COVID-19 , Humans , Adolescent , Angiotensin Receptor Antagonists/therapeutic use , Telmisartan/therapeutic use , COVID-19/drug therapy , SARS-CoV-2 , Renin-Angiotensin System
5.
J Am Heart Assoc ; 9(22): e017364, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-2064368

ABSTRACT

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes the angiotensin-converting enzyme-2 (ACE-2) receptor to enter human cells. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) are associated with ACE-2 upregulation. We hypothesized that antecedent use of ACEI/ARB may be associated with mortality in coronavirus disease 2019 (COVID-19). Methods and Results We used the Coracle registry, which contains data of patients hospitalized with COVID-19 in 4 regions of Italy, and restricted analyses to those ≥50 years of age. The primary outcome was in-hospital mortality. Among these 781 patients, 133 (17.0%) used an ARB and 171 (21.9%) used an ACEI. While neither sex nor smoking status differed by user groups, patients on ACEI/ARB were older and more likely to have hypertension, diabetes mellitus, and congestive heart failure. The overall mortality rate was 15.1% (118/781) and increased with age (PTrend<0.0001). The crude odds ratios (ORs) for death for ACEI users and ARB users were 0.98, 95% CI, 0.60-1.60, P=0.9333, and 1.13, 95% CI, 0.67-1.91, P=0.6385, respectively. After adjusting for age, hypertension, diabetes mellitus, and congestive heart failure, antecedent ACEI administration was associated with reduced mortality (OR, 0.55; 95% CI, 0.31-0.98, P=0.0436); a similar, but weaker trend was observed for ARB administration (OR, 0.58; 95% CI, 0.32-1.07, P=0.0796). Conclusions In those aged ≥50 years hospitalized with COVID-19, antecedent use of ACEI was independently associated with reduced risk of inpatient death. Our findings suggest a protective role of renin-angiotensin-aldosterone system inhibition in patients with high cardiovascular risk affected by COVID-19.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/therapy , Hospitalization , Age Factors , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Humans , Italy , Male , Middle Aged , Protective Factors , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
7.
Front Immunol ; 13: 958418, 2022.
Article in English | MEDLINE | ID: covidwho-2022743

ABSTRACT

Purpose: To investigate the clinical predictors of in-hospital mortality in hospitalized patients with Coronavirus disease 2019 (COVID-19) infection during the Omicron period. Methods: All consecutive hospitalized laboratory-confirmed COVID-19 patients between January and May 2022 were retrospectively analyzed. All patients underwent accurate physical, laboratory, radiographic and echocardiographic examination. Primary endpoint was in-hospital mortality. Results: 74 consecutive COVID-19 patients (80.0 ± 12.6 yrs, 45.9% males) were included. Patients who died during hospitalization (27%) and those who were discharged alive (73%) were separately analyzed. Compared to patients discharged alive, those who died were significantly older, with higher comorbidity burden and greater prevalence of laboratory, radiographic and echographic signs of pulmonary and systemic congestion. Charlson comorbidity index (CCI) (OR 1.76, 95%CI 1.07-2.92), neutrophil-to-lymphocyte ratio (NLR) (OR 1.24, 95%CI 1.10-1.39) and absence of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs) therapy (OR 0.01, 95%CI 0.00-0.22) independently predicted the primary endpoint. CCI ≥7 and NLR ≥9 were the best cut-off values for predicting mortality. The mortality risk for patients with CCI ≥7, NLR ≥9 and not in ACEI/ARBs therapy was high (86%); for patients with CCI <7, NLR ≥9, with (16.6%) or without (25%) ACEI/ARBs therapy was intermediate; for patients with CCI <7, NLR <9 and in ACEI/ARBs therapy was of 0%. Conclusions: High comorbidity burden, high levels of NLR and the undertreatment with ACEI/ARBs were the main prognostic indicators of in-hospital mortality. The risk stratification of COVID-19 patients at hospital admission would help the clinicians to take care of the high-risk patients and reduce the mortality.


Subject(s)
COVID-19 , Renin-Angiotensin System , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/drug therapy , Comorbidity , Female , Hospital Mortality , Humans , Lymphocytes , Male , Neutrophils , Retrospective Studies
8.
Hypertension ; 79(11): 2601-2610, 2022 11.
Article in English | MEDLINE | ID: covidwho-2020594

ABSTRACT

BACKGROUND: Cardiovascular diseases including arterial hypertension are common comorbidities among patients hospitalized due to COVID-19. We assessed the influence of preexisting hypertension and its pharmacological treatment on in-hospital mortality in patients hospitalized with COVID-19. METHODS: We studied all consecutive patients who were admitted to the University Hospital in Krakow, Poland, due to COVID-19 between March 2020 and May 2021. Data of 5191 patients (mean age 61.9±16.7 years, 45.2% female) were analyzed. RESULTS: The median hospitalization time was 14 days, and the mortality rate was 18.4%. About a quarter of patients had an established cardiovascular disease including coronary artery disease (16.6%) or stroke (7.6%). Patients with hypertension (58.3%) were older and had more comorbidities than patients without hypertension. In multivariable logistic regression analysis, age above median (64 years), male gender, history of heart failure or chronic kidney disease, and higher C-reactive protein level, but not preexisting hypertension, were independent risk factors for in-hospital death in the whole study group. Patients with hypertension already treated (n=1723) with any first-line antihypertensive drug (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, or thiazide/thiazide-like diuretics) had a significantly lower risk of in-hospital death (odds ratio, 0.25 [95% CI, 0.2-0.3]; P<0.001) compared to nontreated hypertensives (n=1305). CONCLUSIONS: Although the diagnosis of preexisting hypertension per se had no significant impact on in-hospital mortality among patients with COVID-19, treatment with any first-line blood pressure-lowering drug had a profound beneficial effect on survival in patients with hypertension. These data support the need for antihypertensive pharmacological treatment during the COVID-19 pandemic.


Subject(s)
COVID-19 , Cardiovascular Diseases , Hypertension , Humans , Male , Female , Middle Aged , Aged , Antihypertensive Agents/therapeutic use , COVID-19/complications , Pandemics , Hospital Mortality , Hypertension/complications , Hypertension/drug therapy , Hypertension/chemically induced , Calcium Channel Blockers/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Thiazides/therapeutic use , Cardiovascular Diseases/epidemiology , Hospitalization
11.
J Am Heart Assoc ; 11(17): e026143, 2022 09 06.
Article in English | MEDLINE | ID: covidwho-2001999

ABSTRACT

Background Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. Methods and Results MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all-cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69-1.30]) either overall or in subgroups defined by COVID-19 severity or trial type. Network meta-analysis identified no difference between angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33-1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05-3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. Conclusions This meta-analysis of randomized controlled trials evaluating angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers versus control in patients with COVID-19 found no difference in all-cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID-19.


Subject(s)
Acute Kidney Injury , COVID-19 , Hypertension , Myocardial Infarction , Acute Kidney Injury/chemically induced , Adult , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/therapeutic use , Female , Humans , Male , Myocardial Infarction/drug therapy , Randomized Controlled Trials as Topic , Renin-Angiotensin System
13.
J Renin Angiotensin Aldosterone Syst ; 2022: 9028969, 2022.
Article in English | MEDLINE | ID: covidwho-1997252

ABSTRACT

Angiotensin-converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase and is crucial in the renin-angiotensin-aldosterone system (RAAS) but also implicated in immune regulation. Intrinsic ACE has been detected in several immune cell populations, including macrophages and neutrophils, where its overexpression results in enhanced bactericidal and antitumour responses, independent of angiotensin II. With roles in antigen presentation and inflammation, the impact of ACE inhibitors must be explored to understand how ACE inhibition may impact our ability to clear infections or malignancy, particularly in the wake of the coronavirus (SARS-CoV2) pandemic and as antibiotic resistance grows. Patients using ACE inhibitors may be more at risk of postsurgical complications as ACE inhibition in human neutrophils results in decreased ROS and phagocytosis whilst angiotensin receptor blockers (ARBs) have no effect. In contrast, ACE is also elevated in certain autoimmune diseases such as rheumatoid arthritis and lupus, and its inhibition benefits patient outcome where inflammatory immune cells are overactive. Although the ACE autoimmune landscape is changing, some studies have conflicting results and require further input. This review seeks to highlight the need for further research covering ACE inhibitor therapeutics and their potential role in improving autoimmune conditions, cancer, or how they may contribute to immunocompromise during infection and neurodegenerative diseases. Understanding ACE inhibition in immune cells is a developing field that will alter how ACE inhibitors are designed in future and aid in developing therapeutic interventions.


Subject(s)
Angiotensin Receptor Antagonists , COVID-19 , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Humans , RNA, Viral , Renin-Angiotensin System , SARS-CoV-2
15.
Curr Opin Cardiol ; 37(5): 419-423, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-1973297

ABSTRACT

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mostly uses the angiotensin-converting enzyme 2 (ACE-2) as cellular receptor for entering the host cells. Some, but not all, animal studies have shown that renin-angiotensin-aldosterone system (RAAS) inhibitors can increase ACE-2 expression. On that premise, it was hypothesized that these agents could make it more likely to develop coronavirus disease 2019 (COVID-19). On the other hand, there was also evidence that being on these agents could lessen the severity of the lung injury in patients with severe SARS-CoV-2 infection. Herein, we review the available evidence on the role of RAAS inhibitors on SARS-CoV-2 and COVID-19 development. RECENT FINDINGS: Recent randomized controlled trials demonstrate that RAAS blockade or withdrawal does not influence the severity of COVID-19 in patients who are already on these medications. Currently, there is no evidence to support stopping RAAS inhibitors in patients hospitalized for COVID-19. Several questions still need to be addressed. Ongoing studies are currently evaluating the de novo use of RAAS inhibitors in patients with COVID-19. Another area that needs to be investigated is whether or not using these medications increase the risk of infection. SUMMARY: The wealth of evidence indicates that ACE inhibitors and angiotensin-receptor blocker administration has no harmful effects on hospitalizations and severity of COVID-19 in patients already on these medications and might even reduce mortality among hypertensive patients diagnosed with COVID-19. More evidence and data need to be collected, and at this time, these agents should not be discontinued.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/therapeutic use , Animals , COVID-19/drug therapy , Humans , Hypertension/drug therapy , Renin-Angiotensin System , SARS-CoV-2
16.
Molecules ; 27(15)2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1969391

ABSTRACT

Angiotensin receptor blockers (ARBs) used in the treatment of hypertension and potentially in SARS-CoV-2 infection exhibit inverse agonist effects at angiotensin AR1 receptors, suggesting the receptor may have evolved to accommodate naturally occurring angiotensin 'antipeptides'. Screening of the human genome has identified a peptide (EGVYVHPV) encoded by mRNA, complementary to that encoding ANG II itself, which is an inverse agonist. Thus, opposite strands of DNA encode peptides with opposite effects at AR1 receptors. Agonism and inverse agonism at AR1 receptors can be explained by a receptor 'switching' between an activated state invoking receptor dimerization/G protein coupling and an inverse agonist state mediated by an alternative/second messenger that is slow to reverse. Both receptor states appear to be driven by the formation of the ANG II charge-relay system involving TyrOH-His/imidazole-Carboxylate (analogous to serine proteases). In this system, tyrosinate species formed are essential for activating AT1 and AT2 receptors. ANGII is also known to bind to the zinc-coordinated metalloprotease angiotensin converting enzyme 2 (ACE2) used by the COVID-19 virus to enter cells. Here we report in silico results demonstrating the binding of a new class of anionic biphenyl-tetrazole sartans ('Bisartans') to the active site zinc atom of the endopeptidase Neprilysin (NEP) involved in regulating hypertension, by modulating humoral levels of beneficial vasoactive peptides in the RAS such as vasodilator angiotensin (1-7). In vivo and modeling evidence further suggest Bisartans can inhibit ANG II-induced pulmonary edema and may be useful in combatting SARS-CoV-2 infection by inhibiting ACE2-mediated viral entry to cells.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/drug therapy , Humans , Hypertension/drug therapy , Neprilysin/metabolism , Peptidyl-Dipeptidase A/metabolism , Proto-Oncogene Mas , Receptors, Angiotensin/metabolism , Renin-Angiotensin System , SARS-CoV-2 , Zinc/pharmacology
17.
Crit Care Med ; 50(10): e744-e758, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-1961176

ABSTRACT

OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. SUBJECTS: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.


Subject(s)
COVID-19 , Hypertension , Adult , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/drug therapy , Humans , Hypertension/drug therapy , Male , Middle Aged , Renin-Angiotensin System , Retrospective Studies
18.
BMJ Open ; 12(7): e060305, 2022 07 06.
Article in English | MEDLINE | ID: covidwho-1923253

ABSTRACT

OBJECTIVES: Evaluate the associations between patients taking ACE inhibitors and angiotensin receptor blockers (ARBs) and their clinical outcomes after an acute viral respiratory illness (AVRI) due to COVID-19. DESIGN: Retrospective cohort. SETTING: The USA; 2017-2018 influenza season, 2018-2019 influenza season, and 2019-2020 influenza/COVID-19 season. PARTICIPANTS: People with hypertension (HTN) taking an ACEi, ARB or other HTN medications, and experiencing AVRI. MAIN OUTCOME MEASURES: Change in hospital admission, intensive care unit (ICU) or coronary care unit (CCU), acute respiratory distress (ARD), ARD syndrome (ARDS) and all-cause mortality, comparing COVID-19 to pre-COVID-19 influenza seasons. RESULTS: The cohort included 1 059 474 episodes of AVRI (653 797 filled an ACEi or ARB, and 405 677 other HTN medications). 58.6% were women and 72.9% with age ≥65. The ACEi/ARB cohort saw a larger increase in risk in the COVID-19 influenza season than the other HTN medication cohort for four out of five outcomes, with an additional 1.5 percentage point (pp) increase in risk of an inpatient stay (95% CI 1.2 to 1.9 pp) and of ICU/CCU use (95% CI 0.3 to 2.7 pp) as well as a 0.7 pp (0.1 to 1.2 pp) additional increase in risk of ARD and 0.9 pp (0.4 to 1.3 pp) additional increase in risk of ARDS. There was no statistically significant difference in the absolute risk of death (-0.2 pp, 95% CI -0.4 to 0.1 pp). However, the relative risk of death in 2019/2020 versus 2017/2018 for the ACEi/ARB group was larger (1.40 (1.36 to 1.44)) than for the other HTN medication cohort (1.24 (1.21 to 1.28)). CONCLUSIONS: People with AVRI using ACEi/ARBs for HTN had a greater increase in poor outcomes during the COVID-19 pandemic than those using other medications to treat HTN. The small absolute magnitude of the differences likely does not support changes in clinical practice.


Subject(s)
COVID-19 , Hypertension , Influenza, Human , Respiratory Distress Syndrome , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Cohort Studies , Female , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Male , Outpatients , Pandemics , Renin-Angiotensin System , Retrospective Studies
19.
J Med Virol ; 94(10): 4727-4734, 2022 10.
Article in English | MEDLINE | ID: covidwho-1905892

ABSTRACT

Comorbidities such as hypertension could exacerbate symptoms of coronaviral disease 2019 (COVID)-19 infection. Patients with hypertension may receive both anti-COVID-19 and antihypertension therapies when infected with COVID-19. However, it is not clear how different classes of anti-hypertension drugs impact the outcome of COVID-19 treatment. Herein, we explore the association between the inpatient use of different classes of anti-hypertension drugs and mortality among patients with hypertension hospitalized with COVID-19. We totally collected data from 278 patients with hypertension diagnosed with COVID-19 admitted to hospitals in Wuhan from February 1 to April 1, 2020. A retrospective study was conducted and single-cell RNA-sequencing (RNA-Seq) analysis of treatment-related genes was performed. The results showed that Angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) drugs significantly increased the survival rate but the use of angiotensin-converting enzyme inhibitor/ß-block/diuretic drugs did not affect the mortality caused by COVID-19. Based on the analysis of four public data sets of single-cell RNA-Seq on COVID-19 patients, we concluded that JUN, LST1 genes may play a role in the effect of ARB on COVID-19-related mortality, whereas CALM1 gene may contribute to the effect of CCB on COVID-19-related mortality. Our results provide guidance on the selection of antihypertension drugs for hypertensive patients infected with COVID-19.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Calcium Channel Blockers/therapeutic use , Computational Biology , Humans , Hypertension/complications , Hypertension/drug therapy , Retrospective Studies , SARS-CoV-2
20.
Rev Port Cardiol ; 41(10): 823-830, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1907718

ABSTRACT

Background: Chronic use of Angiotensin-converting enzyme (ACE) inhibitors (ACEi) and aldosterone-receptor blockers (ARB) is not associated with worse outcomes in patients with COVID-19. However, evidence on the impact of their discontinuation during hospital admission is scarce. Our aim was to determine whether withdrawal of ACEi, ARB and mineralocorticoid receptor antagonists (MRA) is associated with all-cause mortality in a real-life large cohort of patients with SARS-CoV-2 infection. Methods: Observational cohort study from a large referral center from 1 March 2020 to 20 April 2020. Withdrawal of renin-angiotensin-aldosterone system inhibitors was defined as the absence of any received dose during hospital admission in patients receiving chronic treatment. Prescriptions during admission were confirmed by data from the central pharmacy computerized system. Results: A total of 2042 patients (mean age 68.4±17.6, 57.1% male) with confirmed COVID-19 were included. During a median follow-up of 57 (21-55) days, 583 (28.6%) died. Prior to hospital admission 468 (22.9%), 343 (16.8%) and 83 (4.1%) patients were receiving ACEi, ARB and MRA respectively. During the study period, 216 (46.2%), 193 (56.3%) and 41 (49.4%) were withdrawn from the corresponding drug. After adjusting for age, cardiovascular risk factors, baseline comorbidities and in-hospital COVID-19 dedicated treatment, withdrawal of ACE inhibitors (hazard ration [HR] 1.48 [95% confidence interval -CI- 1.16-1.89]) and MRA (HR 2.01 [95% CI 1.30-3.10]) were shown to be independent predictors of all-cause mortality. No independent relationship between ARB withdrawal and mortality was observed. Conclusion: ACEi and MRA withdrawal were associated with higher mortality. Strong consideration should be given to not discontinuing these medications during hospital admission.


Introdução: O uso crónico de inibidores da ECA (IECA) e de antagonistas dos recetores de aldosterona (ARA) não está associado a resultados piores em doentes com Covid-19. No entanto, a evidência relativa ao impacto da sua retirada durante a admissão hospitalar é escassa. O nosso objetivo foi determinar se a retirada do IECA, ARA e antagonistas dos recetores dos mineralocorticóides (ARM) está associada à mortalidade por todas as causas numa grande coorte real de doentes com infeção por SRA-CoV-2. Métodos: Estudo coorte observacional a partir de um grande centro de referência de 1 de março de 2020 a 20 de abril de 2020. A retirada dos inibidores do sistema RAAS foi definida como a ausência de qualquer dose recebida durante a admissão hospitalar em doentes que recebem tratamento prolongado. As prescrições durante a admissão foram confirmadas por dados do sistema informático da farmácia central. Resultados: Um total de 2042 doentes (idade média de 68,4 ±17,6, 57,1% do sexo masculino) com COVID-19 confirmado foram incluídos. Durante um acompanhamento médio de 57 (21-55) dias, 583 (28,6%) morreram. Conclusão: A retirada do IECA e do ARM foi associada a uma mortalidade mais elevada. Deve ser dada grande atenção para não interromper estes medicamentos durante a admissão hospitalar.


Subject(s)
COVID-19 , Aged , Aged, 80 and over , Aldosterone , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensins , Antihypertensive Agents/therapeutic use , COVID-19/drug therapy , Female , Humans , Male , Middle Aged , Mineralocorticoid Receptor Antagonists/therapeutic use , Renin , Retrospective Studies , SARS-CoV-2
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