The controversy of using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in COVID-19 patients

Abstract

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). In December 2019, a respiratory illness was reported in the city of Wuhan, China and this was reported to be caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), a novel strain of coronavirus and later named as coronavirus disease 2019 (COVID-19). Human to human transmission of the virus was confirmed by the World Health Organization (WHO) on the 21st January 2020.1 By this point, the virus had already spread beyond China’s borders, and a pandemic was subsequently declared by WHO on 11th March 2020.1 At the time of writing, there have been 66,623,914 confirmed cases in 191 countries with 1,530,296 global deaths.2 As the reach of the disease extended, it became apparent that certain factors such as age,3 sex,4 and ethnicity5 may leave certain populations more vulnerable to the virus. As with previous coronavirus outbreaks, such as SARS in 2002 and Middle East Respiratory Syndrome (MERS) over 2012–2014, it has been established that patients with underlying cardiovascular disease (CVD) and hypertension are particularly susceptible to COVID19. Early in the pandemic, a cohort study of 191 patients in the city of Wuhan found that 48% of hospitalized patients had a comorbidity; this was reported in 67% in those who died of the virus. Of these patients, 30% had hypertension and 8% had underlying CVD (48% and 13%, respectively, in those who died).6 Furthermore, findings of a large-scale analysis by the Chinese Centre for Disease Control and Prevention revealed that the case fatality rate of individuals with comorbid CVD was 10.5%, and those with comorbid hypertension was 6.0%. The fatality rate amongst patients with CVD was considerably greater than those with other comorbidities, including those with previous diagnoses of chronic respiratory disease (6.3%) or cancer (5.6%) and much higher than the overall fatality rate (2.3%).7 Throughout the pandemic, numerous studies from various countries have echoed these early findings—CVD and hypertension are common comorbidities in patients with COVID-19, importantly in those who develop severe disease. In addition to the concerning evidence surrounding hypertension and COVID-19, the possibility of adverse outcomes resulting from drug-disease interactions is another pertinent issue. The use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in patients with COVID-19 has become a highly researched topic. National Institute for Health and Care Excellence (NICE) guidelines recommend using ACEi/ARBs in the first-line management of hypertensive patients age <55 and not of Black African or African-Caribbean origin.8 Given the widespread use of ACEi and ARBs in managing hypertension and other CVD, concerns arose due to conflicting evidence surrounding the potential for antihypertensive medication to progress the disease. This is due to the mechanism of viral entry into cells. The interaction between viral spike (S) protein on SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) is crucial in initiating the entrance of the virus into host cells.9 It has been theorized that ACEi and ARBs upregulate the expression of ACE2—this has been shown in animal models.10,11 The meta-analysis by Yang et al.12 was performed investigating the effects of ACEi and ARB in hypertensive patients with confirmed COVID-19 infection. They performed a literature search for relevant terms including “ACEi,” “ARB,” “COVID-19,” and their variants. After The controversy of using angiotensinconverting enzyme inhibitors and angiotensin receptor blockers in COVID-19 patients