Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care
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Abstract
Introduction
Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality.
Methods
We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome.
Results
The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality.
Conclusion
Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.
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SciScore for 10.1101/2020.09.17.20196469: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethical approval: The THIN data collection scheme and research carried out using THIN data were approved by the NHS South-East Multicentre Research Ethic Committee in 2003. Randomization not detected. Blinding not detected. Power Analysis Considering the prevalence of hypertension to be 30%,(18) and the THIN database constituting more than 2 million active patients, we expected to have sufficient power to detect differences in the incidence rates of the primary outcome. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged …
SciScore for 10.1101/2020.09.17.20196469: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethical approval: The THIN data collection scheme and research carried out using THIN data were approved by the NHS South-East Multicentre Research Ethic Committee in 2003. Randomization not detected. Blinding not detected. Power Analysis Considering the prevalence of hypertension to be 30%,(18) and the THIN database constituting more than 2 million active patients, we expected to have sufficient power to detect differences in the incidence rates of the primary outcome. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Strengths and limitations: The primary outcome of suspected or confirmed COVID-19 may not have been well recorded in primary care records. Relatively little testing for COVID-19 occurred early in the pandemic and data flows from COVID-19 testing centres and hospitals to primary care has generally been suboptimal. However, we expect this effect to have been equally distributed across all our included drug exposure cohorts and should therefore not have biased our effect estimates. We also did not have access to data on hospitalisations or cause-specific mortality. Because of the low numbers of deaths in each drug exposure cohort, we did not have sufficient statistical power to assess the association between drug exposures and COVID-19 mortality. We also had insufficient data on ethnicity and socioeconomic status to include this in our analyses, both of which are known to be associated with COVID-19. The strengths of the study include the study design, which attempted to control for confounding by indication bias and adjust for a large number of known risk factors for COVID-19. We also performed multiple sensitivity analyses to check the robustness of our findings in comparison with other published studies. Implications for practice, policy and research: Despite initial concerns about the safety of ACE inhibitors in the context of SARS-CoV-2 pathophysiology, they appear to have no effect on susceptibility to COVID-19 compared to the use of CCBs. Our findings should provide furth...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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