Antihypertensive drugs and risk of COVID-19?
Authors: Joshua D Brown
Journal: The Lancet Respiratory Medicine (2020)

Lei Fang and colleagues1Fang L Karakiulakis G Roth M Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?.Lancet Respir Med. 2020; (published online March 11.)https://doi.org/10.1016/S2213-2600(20)30116-8Summary Full Text Full Text PDF Scopus (2099) Google Scholar extrapolated results from a molecular study of coronaviruses, which showed that this group of viruses uses angiotensin-converting enzyme 2 (ACE2) to target cells on the epithelium of the lungs, intestine, kidneys, and blood vessels.2Wan Y Shang J Graham R Baric RS Li F Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus.J Virol. 2020; 94: e00127-e00130Crossref PubMed Scopus (3178) Google Scholar Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), would probably share these properties. ACE2 is upregulated by antagonists along the renin–angiotensin system, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which are common antihypertensive drugs used to treat patients with hypertension and diabetes. Whether an association exists between increased ACE2 expression and risk of infection with SARS-CoV-2 or severity of COVID-19 is currently not understood. Nevertheless, Fang and colleagues1Fang L Karakiulakis G Roth M Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?.Lancet Respir Med. 2020; (published online March 11.)https://doi.org/10.1016/S2213-2600(20)30116-8Summary Full Text Full Text PDF Scopus (2099) Google Scholar suggested alternative treatment could be sought for those at high risk of infection, and broader public knowledge of this hypothesis has led to increasing uncertainty and concern. Clinical societies have reinforced that there is currently not enough information to make recommendations and have reiterated that patients should not discontinue treatment. Regardless, many patients are seeking strategies to reduce their risk and might discontinue treatment with or without direction from their care providers. In response to this action, it is prudent to consider whether discontinuation of ACEIs and ARBs is safe in such patients and if alternative drugs are needed. This information is intended not to supersede clinical society statements but, rather, supply information in situations in which patients are adamant in their desire to discontinue ACEIs or ARBs. Discontinuation of antihypertensive drugs in response to pathogens and pandemics has not been recorded in published work. Thus, a review of studies investigating general discontinuation of antihypertensive drugs is warranted, including results from population-based hypertension studies that include washout periods. Although specific antihypertensive agents were not reported in a cohort of patients with previous cardiovascular disease,3Beeftink MM van der Sande NG Bots ML et al.Safety of temporary discontinuation of antihypertensive medication in patients with difficult-to-control hypertension.Hypertension. 2017; 69: 927-932Crossref PubMed Scopus (21) Google Scholar discontinuation of antihypertensive drugs was well tolerated. However, 14% (82 of 604) of patients in that study had side-effects and needed so-called escape treatment to avoid dangerous blood pressure levels (>180/110 mm Hg) or other disorders. Common adverse events associated with discontinuation include some cardiovascular side-effects, headache, anxiety, chest pain, dizziness, and malaise.3Beeftink MM van der Sande NG Bots ML et al.Safety of temporary discontinuation of antihypertensive medication in patients with difficult-to-control hypertension.Hypertension. 2017; 69: 927-932Crossref PubMed Scopus (21) Google Scholar, 4van der Wardt V Harrison JK Welsh T Conroy S Gladman J Withdrawal of antihypertensive medication: a systematic review.J Hypertens. 2017; 35: 1742-1749Crossref PubMed Scopus (60) Google Scholar In a study in which ACEIs were discontinued,5Vaur L Bobrie G Dutrey-Dupagne C et al.Short-term effects of withdrawing angiotensin converting enzyme inhibitor therapy on home self-measured blood pressure in hypertensive patients.Am J Hypertens. 1998; 11: 165-173Crossref PubMed Scopus (39) Google Scholar the effect on blood pressure was paradoxical, with an immediate increase over 48 h and then a return to baseline or even lower levels. Long-term effects on blood pressure after discontinuation might depend on patient factors, and as far as we know no studies have assessed long-term outcomes. Caution must be practiced when recommending discontinuation or alternative treatment. For patients on multidrug therapy, other antihypertensive agents might not be safe to discontinue and should be continued, particularly central-acting agents such as β-blockers and α2-agonists, which can have severe withdrawal syndromes. Second, if alternative agents are to be suggested, clinical guidelines for selection of these treatments should be followed. Related links•The latest guidance from WHO on ibuprofen and COVID-19 (dated: 19.03.2020)•Statement from Prof Michael Roth on how to interpret the original letter •The latest guidance from WHO on ibuprofen and COVID-19 (dated: 19.03.2020)•Statement from Prof Michael Roth on how to interpret the original letter I declare no competing interests. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?The most distinctive comorbidities of 32 non-survivors from a group of 52 intensive care unit patients with novel coronavirus disease 2019 (COVID-19) in the study by Xiaobo Yang and colleagues1 were cerebrovascular diseases (22%) and diabetes (22%). Another study2 included 1099 patients with confirmed COVID-19, of whom 173 had severe disease with comorbidities of hypertension (23·7%), diabetes mellitus (16·2%), coronary heart diseases (5·8%), and cerebrovascular disease (2·3%). In a third study,3 of 140 patients who were admitted to hospital with COVID-19, 30% had hypertension and 12% had diabetes. Full-Text PDF Antihypertensive drugs and risk of COVID-19?Lei Fang and colleagues1 suggest that clinicians should consider withholding angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) because of a potential increased risk of worse clinical outcomes in patients with coronavirus disease 2019 (COVID-19), and they suggest calcium channel blockers as an alternative. The hypothesis behind this suggestion is that the entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the ACE2 receptor and that ACEIs and ARBs have the potential to upregulate ACE2. Full-Text PDF Antihypertensive drugs and risk of COVID-19?Lei Fang and colleagues1 postulate that because severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor to facilitate host cell entry,2,3 disease severity and mortality of coronavirus disease 2019 (COVID-19) might be increased in patients taking angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) during the COVID-19 pandemic, because the ACE2 receptor might be upregulated with use of ACEIs and ARBs. Full-Text PDF Antihypertensive drugs and risk of COVID-19? – Authors' replyWe thank Joshua Brown, Kevin Lo and colleagues, and Christopher Tignanelli and colleagues for their responses to our Correspondence1, and we welcome the opportunity to reply. Full-Text PDF