Abstract
Objectives: Evidence has shown that angiotensin-converting enzyme 2 (ACE2), which can be upregulated after angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, may play a dual role in the pathogenesis and progression of coronavirus disease 2019 (COVID-19). We aimed to assess the association between the use of ACEi/ARB and the outcome of COVID-19 patients with preexisting hypertension in non-endemic areas.Methods: From January 17, 2020, to February 19, 2020, 286 patients with hypertension were enrolled in this retrospective study out of 1,437 COVID-19 patients from 47 centers in Zhejiang and Jiangsu Province. The composite endpoints consisted of mechanical ventilation, intensive care unit (ICU) admission, or death. Cox proportional hazards analysis was performed to assess the association between ACEi/ARB and clinical outcomes of COVID-19 patients with hypertension.Results: In the main analysis, 103 patients receiving ACEi/ARB were compared with 173 patients receiving other regimens. Overall, 44 patients (15.94%) had an endpoint event. The risk probability of crude endpoints in the ACEi/ARB group (12.62%) was lower than that in the non-ACEi/ARB group (17.92%). After adjusting for confounding factors by inverse probability weighting, the results showed that the use of ACEi/ARB reduced the occurrence of end events by 47% [hazard ratio (HR) = 0.53; 95% CI, 0.34–0.83]. Similar results were obtained in multiple sensitivity analyses.Conclusions: In this retrospective study, among COVID-19 patients with hypertension, the use of ACEi/ARB is not associated with an increased risk of disease severity compared with patients without ACEi/ARB. The trends of beneficial effects of ACEi/ARB need to be further evaluated in randomized clinical trials.
Highlights
The novel coronavirus disease 2019 (COVID-19) is spreading worldwide, with an increasing number of confirmed cases and deaths, and has received widespread attention from the World Health Organization
Fever and cough were the main symptoms in the Angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) group and other regimens group, and the proportion in the two groups had no significant differences
The results of the sensitivity analyses support our main findings. In this multicenter retrospective study, our results suggest that chronic treatment with ACEi/ARB is not associated with an increased severity of clinical outcome in COVID-19 patients with hypertension
Summary
The novel coronavirus disease 2019 (COVID-19) is spreading worldwide, with an increasing number of confirmed cases and deaths, and has received widespread attention from the World Health Organization. The expression of angiotensin-converting enzyme 2 (ACE2) is upregulated after ACEi and ARB treatment [2]. Patients with a medical history of ACEi/ARB may be more likely to suffer from SARS-COV2 infection and severe progression due to elevated ACE2 expression, and it has proposed that alternative treatments be sought for those with a high risk of infection [4]. Evidence from various acute respiratory distress syndrome (ARDS) animal models showed that exogenous ACE2 supplementation can reduce inflammation and increase oxygenation [2]. ACEi/ARB may, in turn, be beneficial as it prevents RAS overactivation by increasing ACE2 expression, reducing the risk of acute lung injury and acute respiratory distress syndrome
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