Abstract
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share a target receptor with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The use of ACEIs/ARBs may cause angiotensin-converting enzyme 2 receptor upregulation, facilitating the entry of SARS-CoV-2 into host cells. There is concern that the use of ACEIs/ARBs could increase the risks of severe COVID-19 and mortality. The impact of discontinuing these drugs in patients with COVID-19 remains uncertain. We aimed to assess the association between the use of ACEIs/ARBs and the risks of mortality and severe disease in patients with COVID-19. A systematic search was performed in PubMed, EMBASE, Cochrane Library, and MedRxiv.org from December 1, 2019, to June 20, 2020. We also identified additional citations by manually searching the reference lists of eligible articles. Forty-two observational studies including 63,893 participants were included. We found that the use of ACEIs/ARBs was not significantly associated with a reduction in the relative risk of all-cause mortality [odds ratio (OR) = 0.87, 95% confidence interval (95% CI) = 0.75–1.00; I2 = 57%, p = 0.05]. We found no significant reduction in the risk of severe disease in the ACEI subgroup (OR = 0.95, 95% CI = 0.88–1.02, I2 = 50%, p = 0.18), the ARB subgroup (OR = 1.03, 95% CI = 0.94–1.13, I2 = 62%, p = 0.48), or the ACEI/ARB subgroup (OR = 0.83, 95% CI = 0.65–1.08, I2 = 67%, p = 0.16). Moreover, seven studies showed no significant difference in the duration of hospitalization between the two groups (mean difference = 0.33, 95% CI = −1.75 to 2.40, p = 0.76). In conclusion, the use of ACEIs/ARBs appears to not have a significant effect on mortality, disease severity, or duration of hospitalization in COVID-19 patients. On the basis of the findings of this meta-analysis, there is no support for the cessation of treatment with ACEIs or ARBs in patients with COVID-19.
Highlights
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has initiated a global epidemic
We used the following medical subject headings and keywords to search for articles related to COVID-19: COVID-19, severe acute respiratory syndrome coronavirus 2, 2019-nCoV, and SARS-CoV-2; and the following search terms related to Angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs): renin–angiotensin system, angiotensinconverting enzyme inhibitor, and angiotensin II receptor blockers (Supplementary Table 1)
The concerns about the use of ACEIs or ARBs in patients with COVID-19 have mainly stemmed from arguments based on biologic plausibility, the observation that ACEIs and ARBs have the potential to upregulate angiotensin-converting enzyme 2 (ACE2) receptors [60]
Summary
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has initiated a global epidemic. Because RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), increase the levels of ACE2, the protein that facilitates the entry of SARS-CoV-2 into cells, there are concerns that these drugs could increase the risks of severe COVID-19 and mortality [4]. Evidence that ACEIs and ARBs might upregulate ACE2 in several organs, including the lungs and heart [5], supported the hypothesis widely reported by the press that their use might increase susceptibility to infection with SARS-CoV-2 and that their discontinuation might be an appropriate preventive measure [6]. Based on these facts and observations, the hypothesis has been developed that their use may affect human susceptibility to infection with SARS-CoV-2
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