COVID-19 treatment: study evaluates ACEi and ARB effects on clinical outcomes

In a recent study published in the Scientific Reports Journal, a group of researchers compared the effects of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) on inpatient mortality and hospital stay duration in patients suffering from coronavirus disease 2019 (COVID-19).

Study: Comparing clinical outcomes of ARB and ACEi in patients hospitalized for acute COVID-19. Image Credit: CKA/


As of April 2022, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed 6.2 million lives.

The virus enters human cells via the angiotensin-converting enzyme 2 (ACE2) receptor, part of the Renin–Angiotensin–Aldosterone system. Therefore, decreasing ACE2 expression could reduce infection risk but may exacerbate disease severity.

ACEIs and ARBs, which increase ACE2 expression, have sparked controversy. Some studies suggest they increase severe disease risk, while others showed no association or beneficial outcomes.

A meta-analysis of 101,949 COVID-19 patients found a significant reduction in death and severe adverse events among those receiving ACEIs or ARBs. However, the clinical superiority between ACEIs and ARBs remains unclear.

About the study

The present study utilized the Diagnosis and Procedure Combination (DPC) data, the largest nationwide hospital administrative database in Japan, obtained from 438 out of 1,750 acute care hospitals, representing 25% of all hospitals.

The DPC dataset, collected by Medical Data Vision (MDV), included information from January 1, 2010, to November 30, 2021, encompassed patients of all ages with confirmed acute COVID-19 requiring hospital admission.

The dataset provided details such as demographics, diagnoses, comorbidities, prescriptions, procedures, clinical outcomes, and length of hospital stay. Patients prescribed ACEi or ARB within 30 days prior to admission were identified and included, while those on neither medication were excluded.

Baseline characteristics, including smoking history, body mass index, and baseline diseases, were collected using the International Classification of Diseases, tenth revision (ICD-10) coding. Missing data for smoking history and body mass index were imputed using multiple imputations.

The dataset also included information on complications, treatment modalities, oxygen therapy, mechanical ventilation, renal replacement therapy, in-hospital mortality, and duration of hospitalization.

Statistical analyses performed by the researchers involved logistic or linear regression models, adjusting for baseline clinical characteristics and propensity score analyses. The Muribushi Okinawa Ethics Committee approved the study.

Study results

The study results showed that between January 2020 and November 2021, a total of 67,348 inpatients with COVID-19 were identified.

Among them, 7,613 patients were receiving either ARB or ACEi and were included in the study. The ARB group comprised 6,193 patients, while the ACEi group comprised 710 patients.

Further, baseline characteristics showed that compared to individuals on ACEi, those on ARB were more likely to be female, younger, hypertensive, obese, or suffering from chronic kidney diseases (CKD grade 5D).

On the other hand, the ACEi group had a higher prevalence of heart failure, ischemic heart disease, dementia, arrhythmia, or iron deficiency anemia. There were no significant differences in smoking history, cerebrovascular disease, history of diabetes mellitus, chronic kidney disease (except CKD grade 5D), liver cirrhosis, peripheral vascular disease, or cancer.

In terms of treatment and complications, the ARB group had a higher likelihood of receiving dexamethasone or glucocorticoids as well as renal replacement therapy (RRT), but a lower likelihood of receiving extracorporeal membrane oxygenation, invasive mechanical ventilation (IMV), vasopressors, or blood transfusion.

There were no significant differences in the proportion of non-invasive positive pressure therapy, oxygen therapy or RRT in patients without hemodialysis prior to admission.

Regarding short-term complications within 30 days of COVID-19 diagnosis, patients on ARB had a lower likelihood of experiencing atrial fibrillation or acute ischemic heart disease (aIHD).

There were no differences in cardiopulmonary arrest (CPA), septic shock, disseminated intravascular coagulation (DIC), acute kidney injury (AKI), pulmonary embolism (PE), acute myocarditis, brain infarction (BI), or subarachnoid/intracranial hemorrhage (SAH/ICH).

As for long-term complications (a month or more after diagnosis), the ARB group had a lower incidence of deep vein thrombosis (DVT), but no significant differences were observed in other complications.

In terms of clinical outcomes, the crude in-hospital mortality rate was lower in the ARB group, but after adjusting for multiple factors, there was no significant difference in in-hospital mortality between the ACEi and ARB groups.

The ARB group had lower odds of developing acute respiratory distress syndrome (ARDS) and aIHD in crude analysis, but not in adjusted models.

Further, the prevalence of IMV was lower in the ARB group, and after adjusting for baseline characteristics, the odds of IMV remained lower in the ARB group.

Regarding RRT, after excluding patients already on hemodialysis before admission, RRT was more likely to be in the ARB group. The ARB group also had a shorter median length of hospital stay compared to the ACEi group, which remained significant after adjusting for various factors.


To summarize, the study compared the effects of ACEi and ARB in 7,613 COVID-19 patients and found that ARB was initially associated with lower in-hospital mortality, but this difference disappeared after adjustments.

However, ARB use was linked to shorter hospital stays and reduced risks of certain complications.

These findings align with previous studies suggesting the potential benefits of ARBs in COVID-19. Moreover, further research is needed to draw definitive conclusions.

Journal reference:
  • Hamada, S. et al. (2023) "Comparing clinical outcomes of ARB and ACEi in patients hospitalized for acute COVID-19", Scientific Reports, 13(1). doi: 10.1038/s41598-023-38838-8.

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Tags: ACE2, Acute Kidney Injury, Acute Respiratory Distress Syndrome, Aldosterone, Anemia, Angiotensin, Angiotensin-Converting Enzyme 2, Arrhythmia, Atrial Fibrillation, Blood, Blood Transfusion, Body Mass Index, Brain, Cancer, Cerebrovascular Disease, Chronic, Chronic Kidney Disease, Cirrhosis, Coronavirus, Coronavirus Disease COVID-19, covid-19, Deep Vein Thrombosis, Dementia, Dexamethasone, Diabetes, Diabetes Mellitus, Embolism, Enzyme, Heart, Heart Disease, Heart Failure, Hospital, International Classification of Diseases, Iron Deficiency, Ischemic Heart Disease, Kidney, Kidney Disease, Liver, Membrane, Mortality, Myocarditis, Oxygen, Oxygen Therapy, Pulmonary Embolism, Receptor, Renal Replacement Therapy, Renin, Research, Respiratory, SARS, SARS-CoV-2, Septic Shock, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Smoking, Syndrome, Thrombosis, Vascular, Virus

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Written by

Vijay Kumar Malesu

Vijay holds a Ph.D. in Biotechnology and possesses a deep passion for microbiology. His academic journey has allowed him to delve deeper into understanding the intricate world of microorganisms. Through his research and studies, he has gained expertise in various aspects of microbiology, which includes microbial genetics, microbial physiology, and microbial ecology. Vijay has six years of scientific research experience at renowned research institutes such as the Indian Council for Agricultural Research and KIIT University. He has worked on diverse projects in microbiology, biopolymers, and drug delivery. His contributions to these areas have provided him with a comprehensive understanding of the subject matter and the ability to tackle complex research challenges.

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