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

Abstract

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)).

COVID-19: A Comprehensive Review on Cardiovascular Alterations, Immunity, and Therapeutics in Older Adults

“…Accordingly, many studies have evaluated the effects of these types of drugs in COVID-19 patients, demonstrating a decrease in morbidity in patients who received treatments with ACEIs or ARBs [ 124 ]. In fact, patients treated with these drugs showed a decrease in the risk of severe disease development compared to patients without treatment [ 125 ].…”

The Importance of Coronary Heart Disease and Arterial Hypertension in Assessing the Risk of Complications in Patients With Covid-19

“…сокращением числа госпитализаций в ОРИТ (9% против 31%, p=0,001), необходимости интубации (7% против 28%, p=0,002) и смертности (2% против 24%, p=0,000). Значительная отрицательная связь между применением ИАПФ или БРА и смертностью также наблюдалась в многофакторном анализе после корректировки на возможные факторы риска (ОШ=0,087, 95% ДИ 0,017-0,449) [17].…”

Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient

“…One of the therapeutic groups which has been and continues to be the focus of most debate is that of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) (Danser et al 2020 ; Fang et al 2020 ; Wysocki et al 2020 ), which are widely used for treatment of cardiovascular diseases such as hypertension and ischaemic heart disease López-Otero et al 2021 ). This controversy arises because ACEIs/ARBs have several mechanisms whereby they can influence COVID-19 outcomes, in some cases with contrary effects: (i) on the one hand, they could increase the risk of COVID-19 outcomes, since in the medium term inhibition of ACE2 (angiotensin-converting enzyme 2) would bring about an increase in its receptors (Alhaddad et al 2022 ; Asiimwe et al 2022 Udhaya et al, 2021), and this, on being the COVID-19 gateway, would in turn increase susceptibility to the virus (Gómez et al 2020 ; Möhlendick et al 2021 ). Furthermore: (ii) the increase in ACE2 would decrease the effects of angiotensin II involved in the renin–angiotensin–aldosterone system (RAAS), reducing the substrate for conversion of ACE2 into angiotensin 1–7 and so reducing its protective effect in the lung (Asiimwe et al 2022 ), which would increase risk of progression to more severe stages of the disease.…”

“…Furthermore: (ii) the increase in ACE2 would decrease the effects of angiotensin II involved in the renin–angiotensin–aldosterone system (RAAS), reducing the substrate for conversion of ACE2 into angiotensin 1–7 and so reducing its protective effect in the lung (Asiimwe et al 2022 ), which would increase risk of progression to more severe stages of the disease. On the other hand: (iii) it has been seen that an increase in ACE2 (free or blocked by ACEIs/ARBs) could be associated with a decrease in the serum levels of inflammatory markers (Alhaddad et al 2022 ), which would lead to a lower risk of progression to more severe stages among subjects who were COVID-positive (Baral et al 2021 ; Kumar & Banerjee 2021 ; Meng et al 2020 ).…”