Association of renin–angiotensin–aldosterone system inhibition with Covid-19 hospitalization and all-cause mortality in the UK biobank

Abstract

Aims: With growing evidence on the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (Covid-19), we aimed to thoroughly investigate the association between the use of major classes of antihypertensive medications and Covid-19 outcomes in comparison with the use of ACEIs and ARBs. Methods: We conducted a population-based study in patients with pre-existing hypertension in the UK Biobank with data from the first 2 SARS-CoV-2 waves prior population-based vaccination. Multivariable logistic regression analysis was performed adjusting for a wide range of confounders. Results: The use of either β-blockers (BBs), calcium-channel blockers (CCBs) or diuretics was associated with a higher risk of Covid-19 hospitalization compared to ACEI use (adjusted OR (95%CI): 1.66 [1.43–1.93]) and ARB use (1.53 [1.30–1.81]). The risk of 28-day mortality among Covid-19 patients was also increased among users of BBs, CCBs or diuretics when compared to ACEI users (1.74 [1.30–2.33]) but not when compared to ARB users (1.26 [0.93–1.71]). The association between BB, CCB or diuretic use (compared to ACEI use) and 28-day mortality among hospitalized Covid-19 patients narrowly missed statistical significance (1.47 [0.99–2.18]) but it was statistically significant when the analysis was restricted to patients hospitalized during the second SARS-CoV-2 wave (1.80 [1.15–2.83]). Conclusion: Our results suggest protective effects of inhibition of the renin–angiotensin–aldosterone system on Covid-19 hospitalization and mortality, particularly with ACEI, among patients with pharmaceutically treated hypertension. If confirmed by randomized controlled trials, this finding could have high clinical relevance for treating hypertension during the SARS-CoV-2 pandemic.