Association Between Baseline Use of Angiotensin‐Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Death Among Patients Tested for COVID‐19

Thomas, Sarah A.; Puskarich, Michael A.; Pulia, Michael S.; Meltzer, Andrew C.; Camargo, Carlos A.; Courtney, D. Mark; Nordenholz, Kristen E.; Kline, Jeffrey A.; Kabrhel, Christopher

doi:10.1002/jcph.2015

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…Our results are in the line with the results of multiple published studies that reported that the use of RAAS inhibitors is not associated with increased short-term mortality in COVID-19 patients [17,18]. Our results that suggested a protective effect of ACEIs and ARBs are also consistent with the results of a growing number of studies that associated their use in COVID-19 patients a lower risk of mortality [19][20][21][22]. Furthermore, the benefits of ACEIs and ARBs are not limited to the risk of mortality and the outcomes of severity such as ICU admission and use of ventilators.…”

Section: Discussionsupporting

confidence: 92%

Relation Between Renin–Angiotensin–Aldosterone System Inhibitors and COVID-19 Severity

Alhaddad¹,

Almulaify²,

Alwesaibi³

et al. 2022

Cureus

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Background: Angiotensin-converting enzyme 2 (ACE2) receptor serves as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, to enter the lungs. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the expression of ACE2, resulting in concerns that patients with COVID-19 who are receiving these agents may be at increased risk of severe disease. This study was conducted to further investigate the effects of ACEIs and ARBs on the severity of COVID-19 in hospitalized hypertensive patients.Methods: The study was a retrospective observational study. The medical records of all adult hypertensive patients who were hospitalized at Dammam Medical Complex (DMC) between March 1, 2020, and December 31, 2020, due to COVID-19 were reviewed. The hypertensive patients who were receiving ACEIs or ARBs were compared with the other hypertensive patients who were not on ACEIs or ARBs.Results: A total of 148 hypertensive patients were included in the analysis. They consisted of 106 male and 42 female patients (72% and 28%, respectively). Nearly half of the patients were Saudi (75 patients, 50%). A total of 81 patients were in the ACEI/ARB group, and 67 patients were in the control group. There were no differences between the two groups in age, diabetic status, history of chronic kidney disease, initial blood pressure measurements, and initial oxygen requirements, but the control group contained fewer female patients (18% versus 37%) and Saudi patients (36% versus 63%) than the ACEI/ARB group (p-values = 0.017 and 0.002, respectively). The use of ACEIs or ARBs was associated with significant reductions in ICU admission (9% versus 31%, p-value = 0.001), need for intubation (7% versus 28%, p-value = 0.002), and death (2% versus 24%, p-value = 0.000). A significant negative association between the use ACEIs or ARBs and mortality was also observed in the multivariate analysis after the adjustment for the possible confounders, with an odds ratio (OR) of 0.087 and a 95% confidence interval (CI) of 0.017-0.449. Conclusions: ACEIs and ARBs have no adverse effects on the clinical prognosis of COVID-19 patients with hypertension. Their use might be even beneficial and protective, but future larger studies are needed to confirm these effects. In the meanwhile, they should be continued in COVID-19 hypertensive patients unless their use is contraindicated for other reasons (e.g., hypotension, hyperkalemia, or acute kidney injury (AKI)).

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Section: Discussionsupporting

confidence: 92%

Relation Between Renin–Angiotensin–Aldosterone System Inhibitors and COVID-19 Severity

Alhaddad¹,

Almulaify²,

Alwesaibi³

et al. 2022

Cureus

View full text Add to dashboard Cite

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“…In 197 hospitals across the US, symptomatic emergency department patients were collected; renal failure occurred in 548/13,813 (4.0%) and respiratory failure in 2,485/13,880 (17.9%) patients. In SARS-CoV-2-positive patients, baseline ACEi/ARB was linked to a 25% reduced mortality rate after controlling for these covariates [ 22 ].…”

Section: Reviewmentioning

confidence: 99%

SARS-CoV-2 and the Angiotensin-Converting Enzyme 2 Receptor: Angiotensin-Converting Enzyme Inhibitor/Angiotensin 2 Receptor Blocker Utilization and a Shift Towards the Renin-Angiotensin-Aldosterone System Classical Pathway

Felber,

New,

Riskin

2024

Cureus

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, uses the surface angiotensin-converting enzyme 2 (ACE2) receptor as the site of entry into host cardiac, respiratory, intestinal, renal, and nervous system cells. Predisposing risk factors such as cardiovascular disease increase the risk of developing severe disease. Hypertension is characterized by the stimulation of the renin-angiotensin-aldosterone system (RAAS). Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin 2 receptor blockers (ARBs), medications used to treat hypertension, inhibit RAAS and its downstream effects; however, they have also been shown to upregulate ACE2 receptors. In this review, we aim to evaluate the effectiveness of ACEi/ARBs as an adjunct therapy in patients with SARS-CoV-2 as well as examine the possible protective effects and impact on infection rate and disease severity. A PubMed literature search excluding sources outside the United States and duplicates was performed using the following search criteria: “COVID-19 AND cardiovascular disease AND ACEi AND ARB”, “SARS-COVID-19 OR COVID-19, AND ACEi AND ARB AND Infection rate”, “COVID-19 AND ACEi and ARB”, “Omicron BA.1 and BA.2 AND ACE2 OR ARBs”, “Omicron AND ACEi AND ARBs”. This resulted in 33 final sources. The review concluded that ACEi/ARB therapy may continue to improve COVID-19 survival as previous treatment is associated with positive clinical outcomes. Patients taking ACEis or ARBs were found to have a decreased risk of hospitalization, reduced severity of COVID-19 pneumonia, a lesser need for mechanical ventilation, and an overall reduction in mortality rate. No statistically significant association between ACEi/ARB use and enhanced COVID-19 infectivity was found. The Omicron variant is theoretically more infectious and was associated with increased negative clinical outcomes in those undertreated with ACEis/ARBs. The majority of the literature supports the current guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC), and Heart Failure Society of America (HFSA), which state that ACEi and ARB medications should not be withdrawn from or initiated on patients with cardiovascular disease who are infected with SARS-CoV-2. More research needs to be conducted on the association between the emerging COVID-19 variants and ACEis/ARBs to give clinicians confidence when treating patients within this subgroup of the population.

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“…Interestingly, angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs), which increase ACE2 expression, were initially involved in the pathogenesis of SARS-CoV-2 infection, and seem nowadays to be defensive against Covid-19 severity (Thomas et al 2022 ). Similarly, ibuprofen which upregulates ACE2 expression displayed a defensive effect against Covid-19 infection (Poutoglidou et al 2021 ).…”

Section: Fxr and Covid-19mentioning

confidence: 99%

A perspective study of the possible impact of obeticholic acid against SARS-CoV-2 infection

et al. 2022

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The causative agent of CoV disease 2019 is a new coronavirus CoV type 2, affecting the respiratory tract with severe manifestations (SARS-CoV-2). Covid-19 is mainly symptomless, with slight indications in about 85% of the affected cases. Many efforts were done to face this pandemic by testing different drugs and agents to make treatment protocols in different countries. However, the use of these proposed drugs is associated with the development of adverse events. Remarkably, the successive development of SARS-CoV-2 variants which could affect persons even they were vaccinated, prerequisite wide search to find efficient and safe agents to face SARS-CoV-2 infection. Obeticholic acid (OCA), which has anti-inflammatory effects, may efficiently treat Covid-19. Thus, the goal of this perspective study is to focus on the possible medicinal effectiveness in managing Covid-19. OCA is a powerful farnesoid X receptor (FXR) agonist possessing marked antiviral and anti-inflammatory effects. FXR is dysregulated in Covid-19 resulting in hyper-inflammation with concurrent occurrence of hypercytokinemia. Interestingly, OCA inhibits the reaction between this virus and angiotensin-converting enzyme type 2 (ACE2) receptors. FXR agonists control the expression of ACE2 and the inflammatory signaling pathways in this respiratory syndrome, which weakens the effects of Covid-19 disease and accompanied complications. Taken together, FXR agonists like OCA may reveal both direct and indirect impacts in the modulation of immune reaction in SARS-CoV-2 conditions. It is highly recommended to perform many investigations regarding different phases of the discovery of new drugs.

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Association Between Baseline Use of Angiotensin‐Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Death Among Patients Tested for COVID‐19

Cited by 4 publications

References 25 publications

Relation Between Renin–Angiotensin–Aldosterone System Inhibitors and COVID-19 Severity

Relation Between Renin–Angiotensin–Aldosterone System Inhibitors and COVID-19 Severity

SARS-CoV-2 and the Angiotensin-Converting Enzyme 2 Receptor: Angiotensin-Converting Enzyme Inhibitor/Angiotensin 2 Receptor Blocker Utilization and a Shift Towards the Renin-Angiotensin-Aldosterone System Classical Pathway

A perspective study of the possible impact of obeticholic acid against SARS-CoV-2 infection

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