There is some uncertainty among patients and experts as to whether ACE inhibitors and ARBs are associated with an increased risk. Empirical data on this are inconsistent, but there are valid reasons for not discontinuing these drugs for fear of coronavirus infection or during COVID-19 infection.
“Hypertension and other cardiovascular risk factors are not per se associated with an increased susceptibility to infection, whereas cardiovascular pre-existing conditions lead to a severe course and, together with advanced age and male gender, are associated with a poor prognosis,” explained Prof. Franz Eberli, MD, Chief of Cardiology at Stadtspital Triemli, at the web congress event of the Forum for Continuing Medical Education (FomF) on 23.6.2020 [1]. It has not yet been clarified whether persons with hypertension as a sole comorbidity represent a risk group; the evidence on this is inconsistent. In a bivariate analysis of a 2020 study published in JAMA, neither hypertension, diabetes, nor prior cardiovascular disease were found to be independent risk factors for ARDS (acute respiratory distress syndrome) and death in COVID-19 patients [2]. In contrast, a retrospective observational study, also conducted in China, showed a twofold increase in mortality in hypertensive patients [3].
Current motto: Do not discontinue ACE inhibitors and ARBs
The question of whether or not to continue treatment with ACE inhibitors and ARBs in COVID-19 disease is also controversial. After initially circulating the hypothesis that ACE inhibitors and angiotensin II receptor blockers (ARBs) might pose a risk in the context of SARS-CoV-2 infection, three studies published in the New England Journal of Medicine now refute this. These concluded that treatment with ACE inhibitors and ARBs have no adverse effect on the course of COVID-19 disease. Mancia et al. were able to show in a case-control study that there was no increased rate of intubation or mortality, regardless of age and gender [4]. 6272 patients who contracted the virus in northern Italy between February 21 and March 11 were analyzed and compared with 30,759 volunteers matched for age, sex, and residence for medication prescriptions and clinical characteristics. It was found that although the infected patients were more frequently treated with ACE inhibitors or ARBs than the control subjects, they also had an increased use of other antihypertensive drugs such as calcium channel antagonists or beta-blockers. The reason for this is that the infected patients suffered more frequently from cardiovascular diseases such as hypertension than the control subjects. Adjusted for concomitant diseases and other influencing factors, the use of RAAS inhibitors was not significantly associated with the risk of infection, and no association with the severity of the course of infection was found. A cohort study by Reynolds et al. also argues against the hypothesis that RAAS inhibitors favor severe COVID-19 courses [5]. A total of 12 594 patients from New York City were analyzed for data. 46.8% of these tested positive for SARS-CoV-2, of which 17% were classified as severe (on admission to the emergency department, ventilator support, or death). COVID-19 patients who had been treated with RAAS inhibitors, beta-blockers, calcium channel antagonists, or thiazide diuretics were compared with patients without such prescription in terms of prognosis and oucome. Analysis of a propensity score matching showed that none of the antihypertensive classes studied was associated with a substantially increased risk of severe outcome, nor was the risk of infection increased for patients treated with them. In a registry study by Mehra et al. [6] also disproved that RAAS inhibitors increase COVID-19-related mortality risk. A total of 8910 patients from 11 countries who required hospitalization for COVID-19 were included. Multivariate regression analysis showed that neither ACE inhibitor nor ARB use was associated with increased intrahospital mortality risk.
What is known about the interaction between SARS-CoV-2 and RAAS?
“The RAAS system is complex and a simple cause-and-effect mechanism cannot be predicted,” Prof. Eberli explained. During SARS-CoV-2 infection, a decrease in ACE2 was detected on cell surfaces and, at this time, ACE2 is thought to play a critical role in SARS-CoV-2 infection. ACE2 is expressed not only in the heart and vascular system, but also in other organs of the human body (e.g. kidney, lungs, liver). According to a publication by Vaduganathan et al. published in NEJM. [7], SARS-CoV-2 infection causes, first, a decrease in ACE2 on the cell surface and, second, acute lung injury via activation of the RAAS system. Activation of RAAS by SARS-CoV-2 virus contributes to organ damage (lung, heart, kidney). Blocking angiotensin II action by ACE inhibitors or ARBs is potentially beneficial. ACE inhibitors and ARB therapy have been found to reduce mortality in observational studies [3]. Hypertension and discontinuation of hypertensive therapy, on the other hand, are associated with an increased risk of mortality.
Literature:
- Eberli F: COVID-19 and the cardiovascular system. Prof. Franz Eberli, MD, FOMF Internal Medicine, 6/23/20.
- Wu C, et al: Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med 2020; 180(7): 1-11.
- Gao C et al: Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study European Heart Journal 2020; 41: 2058-2066.
- Mancia G, et al: Renin-angiotensin-aldosterone system blockers and the risk of covid-19. N Engl J Med 2020; DOI: 10.1056/NEJMoa2006923.
- Reynolds HR et al. Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19. N Engl J Med 2020; DOI: 10.1056/NEJMoa2008975.
- Mehra M, et al: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19; N Engl J Med 2020; DOI: 10.1056/NEJMoa2007621.
- Vaduganathan M, et al: Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19. Special Report. N Engl J Med 2020; 382: 1653-1659.
HAUSARZT PRAXIS 2020; 15(8): 33 (published 8/16/20, ahead of print).
