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?:abstract
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Background: Mice receiving angiotensin converting enzyme inhibitor (ACEI) drugs show increased susceptibility to infection by Staphylococcus aureus (S aureus) We sought to investigate whether humans using ACEwere at increased risk of S aureus infection, comparing them to users of Angiotensin IReceptor 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 ACEor AR(as an active comparator drug) We regarded prescription of ACEor ARas time-dependent exposure and used a Cox regression model to compare incidence of first hospitalisation with infection due to S aureus in periods with ACEto periods with ARprescriptions We repeated the analysis using control outcomes that we did not expect to be associated with use of ACEversus AR(Gram-negative sepsis, hifracture and herpes zoster) and one that we did (dry cough) Results: We identified 445,341 new users of ACE(mean age 64 0±14 0, male 51 7%) and 41,824 new users of AR(mean age 64 1±14 0, male 45 5%) The fully adjusted hazard ratio for S aureus infection (ACEvs ARB) was 1 18 (95% C1 10–1 27), consistent across sensitivity analyses However, we also found associations with all control outcomes;rates of Gram-negative sepsis, hifracture and dry cough were also increased during periods of time treated with ACEcompared to ARwhile herpes zoster was more common during time treated with ARB Conclusions: Our results suggest that although ARusers appear an ideal control for analyses of ACEeffects, 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
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