The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as an immediate and global problem just within a few months after its first description in Wuhan-China. Beyond its alarming mortality rate and easily transmissible nature through air droplets, it has also resulted in significant challenges in the cardiovascular area not only due to its higher mortality rates in cardiovascular disease and certain associated conditions, including diabetes mellitus and hypertension, but also due to the theoretically facilitated inoculation of lung tissue by the culprit agent, SARS-CoV-2 in these conditions [1,2]. This worrisome concern has been largely attributed to the potential upregulation of angiotensin enzyme 2 (ACE2) in hypertensive and diabetic patients, and more interestingly; in those receiving angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) .
Fortunately, this clinical confusion has been resolved by successive recommendations of cardiovascular societies . Consistently, all guidelines have advised against discontinuation of ACEIs/ARBs in the context of avoiding or treating COVID-19 infection. More interestingly, use of ACEIs and ARBs has been reported to be protective against lung injury caused by COVID-19 particularly in more severe clinical scenarios . Additionally, these agents might also exert anti-inflammatory and antioxidative effects through a significant reduction in angiotensin II levels (with well known oxidative and inflammatory characteristics) along with potentiation of ACE2 (potentially mediating the synthesis of anti-inflammatory and antioxidative byproducts including angiotensin-1–9) that all prevent or mitigate the course of acute respiratory distress syndrome . Clinical trials evaluating the effects of ACEIs, ARBs, and angiotensins themselves in patients with COVID-19 in outpatient and in-patient settings might help to provide important data on this issue. Several studies are currently being conducted to assess role of ACEIs, ARBs, and angiotensins on the clinical course and pathophysiology of COVID-19 (ClinicalTrials.gov identifiers, NCT04364893, NCT04340557, NCT04322786, and NCT04332666). The clinical impact of continuation versus discontinuation of ACEIs and ARBs on outcomes in patients hospitalized with COVID-19 will also be assessed by a randomized clinical study (NCT04338009) (Table 1).
Table 1 -
Studies evaluating the role of renin angiotensin systems on the clinical course of coronavirus disease 2019
ClinicalTrials.gov identifier (NCT number)
|Angiotensin receptor blockers and angiotensin-converting enzyme inhibitors and adverse outcomes in patients with COVID-19
||ARBs and ACEIs
|Do angiotensin receptor blockers mitigate progression to acute respiratory distress syndrome with SARS-CoV-2 infection
|Elimination or prolongation of ACE inhibitors and ARB in coronavirus disease 2019
||Discontinuation of ARB/ACEI
|Continuation of ARB/ACEI
|Angiotensin-(1,7) treatment in COVID-19: the ATCO trial
|The use of angiotensin converting enzyme inhibitors and incident respiratory infections, are they harmful or protective?
|Prognosis of coronavirus disease 2019 (COVID-19) patients receiving antihypertensives
|Efficacy and safety of angiotensin II use in coronavirus disease(COVID)-19 patients with acute respiratory distress syndrome
|Valsartan for prevention of acute respiratory distress syndrome in hospitalized patients with SARS-COV-2 (COVID-19) infection disease
|Losartan for patients with COVID-19 requiring hospitalization
|Losartan for patients with COVID-19 not requiring hospitalization
|Evaluation of clinical parameters on admission and medications in Covid-19 pneumonia (coronavirus disease 2019)
||ACEIs and calcium channel blockers
|Efficacy of captopril in Covid-19 patients with severe acute respiratory syndrome (SARS) CoV-2 pneumonia (CAPTOCOVID)
|Treatments to decrease the risk of hospitalization or death in elderly outpatients with symptomatic SARS-CoV-2 infection (COVID-19)
ARBs, angiotensin receptor blockers; ACEIs, angiotensin-converting enzyme inhibitors; COVID-19, coronavirus disease 2019; SARS, severe acute respiratory syndrome.
Clinicians also need strong recommendations regarding the prescription of these agents for newly diagnosed hypertension cases with or without concomitant conditions, including heart failure (HF), diabetes mellitus, and ischemic heart disease, during the ongoing outbreak of COVID-19. Considering the obscure and multifaceted effects of ACEIs and ARBs in various clinical conditions, it seems plausible to prescribe these agents exclusively for compelling indications (for which these agents are known to be indisputably beneficial), including concomitant heart failure and ischemic heart disease, etc, in the setting of newly diagnosed hypertension. On the other hand, withholding ACEIs or ARBs as the first choice with particular preference of other antihypertensive classes, including calcium antagonist, β-blockers, diuretics, and α-blockers in the absence of compelling indications may eliminate the concerns on the patient’s side and thereby may increase the drug compliance in the setting of newly diagnosed hypertension during the spreading outbreak of COVID-19.
Conflicts of interest
There are no conflicts of interest.
1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020. doi: 10.1001/jama.2020.2648.
2. Tascioglu D, Yalta K, Yetkin E. Hypertension and diabetes mellitus in patients with COVID 19. Cardiovasc Endocrinol Metab. 2020; 9:108–109.
3. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J Virol. 2020; 94:e00127-20.
4. Bavishi C, Maddox TM, Messerli FH. Coronavirus disease 2019 (COVID-19) infection and Renin Angiotensin system blockers. JAMA Cardiol. 2020. doi: 10.1001/jamacardio.2020.1282.
5. Kim J, Choi SM, Lee J, Park YS, Lee CH, Yim JJ, et al. Effect of Renin-Angiotensin system blockage in patients with acute respiratory distress syndrome: a retrospective case control study. Korean J Crit Care Med. 2017; 32:154–163.
6. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005; 436:112–116.