key: cord-0873812-sxm45fe7
authors: Mackey, Katherine; Kansagara, Devan; Vela, Kathryn
title: Update Alert 8: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults
date: 2021-04-27
journal: Ann Intern Med
DOI: 10.7326/l21-0223
sha: 3514fb84f43553d412256c7231ed6f7c8e982582
doc_id: 873812
cord_uid: sxm45fe7

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Because of high confidence based on 78 studies (77 observational studies and 1 randomized controlled trial) in the finding that ACEI or ARB use is not associated with COVID-19 severity, we ended our routine literature surveillance for this key question but planned to report on the findings of 3 in-progress clinic trials. Results are now available for 2 trials that compared COVID-19 severity and mortality in adults who continued or discontinued ACEI or ARB treatment once COVID-19 was diagnosed; the third trial was suspended because of challenges with funding and a low incidence of COVID-19 at the study site (3) (4) (5) .

In the REPLACE COVID (Randomized Elimination or ProLongation of ACEIs and ARBs in COronaVIrus Disease 2019) trial, a randomized, open-label multicenter trial of 152 adults, continuation of ACEIs or ARBs did not result in more severe disease as measured by a composite outcome incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction (6) . Similarly, the BRACE-CORONA (Blockers of Angiotensin Receptor and Angiotensin-Converting Enzyme inhibitors suspension in hospitalized patients with coronavirus infection) trial done in Brazil of 659 adults with mild to moderate COVID-19 found no significant difference in days alive and out of the hospital in the ACEI or ARB continuation group compared with the discontinuation group (7) . These findings support our conclusion that use of ACEIs or ARBs before COVID-19 illness is not associated with increased severity. Because we consider these findings to be stable (meaning that future studies are likely to have the same results), we will retire this key question from our living review.

We identified published results of 1 study in our search-a single-group, open-label trial on the safety of losartan initiation among 34 adults at the University of Kansas Hospital-finding that use of losartan in the intervention group was associated with a lower incidence of adverse events (defined as any untoward medical occurrence in a person during the study) compared with external, nonrandomized controls (8) . This study was not designed to evaluate the effectiveness of losartan in COVID-19 treatment. We previously identified 5 planned or inprogress clinical trials evaluating ACEI or ARB initiation in COVID-19 treatment (Supplement Table) (9-13). Three of these trials remain in progress (9) (10) (11) . Two are complete, but results are not published yet (11, 12) . We will monitor these trials for updates monthly and provide a brief status update in the fall of 2021. When results are available, we will provide an updated evidence synthesis. 

Update alert 7: risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults

Risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults: a living systematic review

Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease

Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors and Adverse Outcomes in Patients With COVID19 (BRACE-CORONA)

COVID-19) ACEi/ARB Investigation (CORONACION)

Accessed at www.clinicaltrials.gov/ct2/show/NCT04330300 on 8

Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial

BRACE CORONA Investigators. Effect of discontinuing vs continuing angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on days alive and out of the hospital in patients admitted with COVID-19: a randomized clinical trial

An open label trial to assess safety of losartan for treating worsening respiratory illness in COVID-19

Efficacy of Captopril in Covid-19 Patients With Severe Acute Respiratory Syndrome (SARS) CoV-2 Pneumonia (CAPTOCOVID) [clinical trial

Angiotensin Converting Enzyme Inhibitors in Treatment of Covid 19

Valsartan for Prevention of Acute Respiratory Distress Syndrome in Hospitalized Patients With SARS-COV-2 (COVID-19) Infection Disease

Losartan for Patients With COVID-19 Not Requiring Hospitalization