Comparisons of Staphylococcus aureus infection and other outcomes between users of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers: lessons for COVID-19 from a nationwide cohort study

Bidulka, Patrick; Iwagami, Masao; Mansfield, Kathryn E.; Kalogirou, Fotini; Wong, Angel; Douglas, Ian; Smeeth, Liam; Summers, Charlotte; Tomlinson, Laurie

doi:10.12688/wellcomeopenres.15873.1

Cited by 3 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, recent studies in humans have identified no difference in ACE2 levels following exposure to ACE or ARB use (Emilsson et al 2020); (Gill et al 2020). Therefore, our findings could also be explained by residual confounding, as suggested by recent comparisons of the incidence of Staphylococcus aureus infection and other outcomes between ACE and ARB use which suggest that ARB is not a perfect comparator for ACE, although no large scale PS-adjustment was used (Bidulka et al 2020).…”

Section: Discussionmentioning

confidence: 95%

Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study

Morales

Conover

You

et al. 2020

Preprint

View full text Add to dashboard Cite

Introduction: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results. Methods: Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) use to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study addressed confounding through large-scale propensity score adjustment and negative control experiments. Results: Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98; 95% CI 0.84 - 1.14), nor any difference for mono/combination use (1.01; 0.90 - 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated a moderately lower risk with ACE, non-significant for monotherapy (0.85; 0.69 - 1.05) and marginally significant for mono/combination users (0.88; 0.79 - 0.99). We observed, however, no significant difference between drug- classes for COVID-19 hospitalization or pneumonia risk across all comparisons. Conclusion: There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.

show abstract

Section: Discussionmentioning

confidence: 95%

Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study

Morales

Conover

You

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“… 49 , 50 , 51 Therefore, our findings could also be explained by residual confounding, as suggested by recent comparisons of the incidence of Staphylococcus aureus infection and other outcomes between ACEI and ARB use, which suggest that ARB use is not a perfect comparator for ACEI use, although no large-scale propensity score adjustment was used. 52 …”

Section: Discussionmentioning

confidence: 99%

“…[49][50][51] Therefore, our findings could also be explained by residual confounding, as suggested by recent comparisons of the incidence of Staphylococcus aureus infection and other outcomes between ACEI and ARB use, which suggest that ARB use is not a perfect comparator for ACEI use, although no large-scale propensity score adjustment was used. 52 Furthermore, one study has reported an increased risk of hospital admission with COVID-19 and intensive care unit admission associated with use of ACEIs and ARBs. 43 Although we did not observe a consistent increased risk of hospital admission with COVID-19, we did observe an increased risk of hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis largely driven by ACEI use compared with CCB or THZ use.…”

Section: Discussionmentioning

confidence: 99%

Renin–angiotensin system blockers and susceptibility to COVID-19: an international, open science, cohort analysis

Moralès¹,

Conover²,

You³

et al. 2021

The Lancet Digital Health

106

View full text Add to dashboard Cite

Background Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension. MethodsIn this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296.Findings Among 1 355 349 antihypertensive users (363 785 ACEI or ARB monotherapy users, 248 915 CCB or THZ monotherapy users, 711 799 ACEI or ARB combination users, and 473 076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0•98, 95% CI 0•84-1•14) or combination use exposure (1•01, 0•90-1•15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0•91, 95% CI 0•68-1•21; with heterogeneity of >40%) or combination use (0•95, 0•83-1•07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0•88, 95% CI 0•79-0•99) and non-significant for monotherapy (0•85, 0•69-1•05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute res...

show abstract

“…or ARBs, the use of ACE-Inhs. was associated with increased rates of S. Aerus and gram-negative infections, while herpes zoster was more commonly associated with ARBs ( Bidulka et al, 2020 ). In addition, the use of ACE-Inhs.…”

Section: Cardiovascular Drugs and Ace2mentioning

confidence: 99%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

View full text Add to dashboard Cite

The recent emergence of coronavirus disease-2019 (COVID-19) as a global pandemic has prompted scientists to address an urgent need for defining mechanisms of disease pathology and treatment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, employs angiotensin converting enzyme 2 (ACE2) as its primary target for cell surface attachment and likely entry into the host cell. Thus, understanding factors that may regulate the expression and function of ACE2 in the healthy and diseased body is critical for clinical intervention. Over 66% of all adults in the United States are currently using a prescription drug and while earlier findings have focused on possible upregulation of ACE2 expression through the use of renin angiotensin system (RAS) inhibitors, mounting evidence suggests that various other widely administered drugs used in the treatment of hypertension, heart failure, diabetes mellitus, hyperlipidemias, coagulation disorders, and pulmonary disease may also present a varied risk for COVID-19. Specifically, we summarize mechanisms on how heparin, statins, steroids and phytochemicals, besides their established therapeutic effects, may also interfere with SARS-CoV-2 viral entry into cells. We also describe evidence on the effect of several vitamins, phytochemicals, and naturally occurring compounds on ACE2 expression and activity in various tissues and disease models. This comprehensive review aims to provide a timely compendium on the potential impact of commonly prescribed drugs and pharmacologically active compounds on COVID-19 pathology and risk through regulation of ACE2 and RAS signaling.

show abstract

Comparisons of Staphylococcus aureus infection and other outcomes between users of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers: lessons for COVID-19 from a nationwide cohort study

Cited by 3 publications

References 21 publications

Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study

Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study

Renin–angiotensin system blockers and susceptibility to COVID-19: an international, open science, cohort analysis

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Contact Info

Product

Resources

About