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

Wellcome Open Research

article

Patrick Bidulka¹  Masao Iwagami¹  Kathryn E. Mansfield¹  Fotini Kalogirou³  Angel Y. S. Wong¹  Ian J. Douglas¹  Liam Smeeth¹  Charlotte Summers³  Laurie A. Tomlinson¹ 

[1] Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine;Department of Health Services Research, Faculty of Medicine, University of Tsukuba;Department of Medicine, Addenbrooke's Hospital, University of Cambridge

关键词: Angiotensin converting enzyme inhibitors;    Angiotensin receptor blockers;    Staphylococcus aureus;    Sepsis;    infection;    COVID-19;   

DOI  :  10.12688/wellcomeopenres.15873.1

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Background: Mice receiving angiotensin converting enzyme inhibitor (ACEI) drugs show increased susceptibility to infection byStaphylococcus aureus (S. aureus). We sought to investigate whether humans using ACEI were at increased risk of S. aureus infection, comparing them to users of Angiotensin II Receptor Blockers (ARB) with multiple control outcomes to assess the potential for residual confounding.Methods: Using the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics between 1997 and 2017, we identified adults starting ACEI or ARB (as an active comparator drug). We regarded prescription of ACEI or ARB as time-dependent exposure and used a Cox regression model to compare incidence of first hospitalisation with infection due toS. aureus in periods with ACEI to periods with ARB prescriptions. We repeated the analysis using control outcomes that we did not expect to be associated with use of ACEI versus ARB (Gram-negative sepsis, hip fracture and herpes zoster) and one that we did (dry cough).Results: We identified 445,341 new users of ACEI (mean age 64.0±14.0, male 51.7%) and 41,824 new users of ARB (mean age 64.1±14.0, male 45.5%). The fully adjusted hazard ratio forS. aureus infection (ACEI vs. ARB) was 1.18 (95% CI 1.10–1.27), consistent across sensitivity analyses. However, we also found associations with all control outcomes; rates of Gram-negative sepsis, hip fracture and dry cough were also increased during periods of time treated with ACEI compared to ARB while herpes zoster was more common during time treated with ARB.Conclusions: Our results suggest that although ARB users appear an ideal control for analyses of ACEI effects, there is residual confounding even after multivariable adjustment. This has implications for observational analyses comparing users of these drug classes, in particular the effect of these drugs in relation to COVID-19 infection.

【 授权许可】

CC BY