Trial reportThe Lancet. Respiratory medicine2021
Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.
Trial report in The Lancet. Respiratory medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04338009 (The Randomized Elimination or Prolongation of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Coronavirus Disease 2019), which is not on this map. Cited by 140 papers, 12 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Randomized Elimination or Prolongation of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Coronavirus Disease 2019
Who cites it
140 citing papers in PubMed, 12 syntheses or guidelines pooled it, 223 citations in OpenAlex.
- Drug treatments for mild or moderate covid-19: systematic review and network meta-analysis.BMJ (Clinical research ed.) · 2025Pooled it
- Withdrawal of antihypertensive drugs in older people.The Cochrane database of systematic reviews · 2025Pooled it
- A Meta-Analysis of the Impact of Using Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin II Receptor Blockers (ARBs) on Mortality, Severity, and Healthcare Resource Utilization in Patients with COVID-19.Advances in respiratory medicine · 2025Pooled it
- Effects of renin-angiotensin system blockers on outcomes from COVID-19: a systematic review and meta-analysis of randomized controlled trials.European heart journal. Cardiovascular pharmacotherapy · 2024Pooled it
- COVID-19 and the Use of Angiotensin II Receptor Blockers in Older Chronic Hypertensive Patients: Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2023Pooled it
- Effect of continuing the use of renin-angiotensin system inhibitors on mortality in patients hospitalized for coronavirus disease 2019: a systematic review, meta-analysis, and meta-regression analysis.BMC infectious diseases · 2023Pooled it
- Cardiovascular drugs and COVID-19 clinical outcomes: a systematic review and meta-analysis of randomized controlled trials.British journal of clinical pharmacology · 2022Pooled it
- 2022 AHA/ACC Key Data Elements and Definitions for Cardiovascular and Noncardiovascular Complications of COVID-19: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards.Journal of the American College of Cardiology · 2022Guideline
- Renin-Angiotensin Aldosterone System Inhibitors and COVID-19: A Systematic Review and Meta-Analysis Revealing Critical Bias Across a Body of Observational Research.Journal of the American Heart Association · 2022Pooled it
- Cardiovascular drugs and COVID-19 clinical outcomes: A living systematic review and meta-analysis.British journal of clinical pharmacology · 2021Pooled it
- In-hospital use of statins is associated with a reduced risk of mortality in coronavirus-2019 (COVID-19): systematic review and meta-analysis.Pharmacological reports : PR · 2021Pooled it
- Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.Frontiers in public health · 2021Pooled it
- Effects of Losartan on Patients Hospitalized for Acute COVID-19: A Randomized Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Trial
- Ramipril for the Treatment of COVID-19: RAMIC, a Randomized, Double-Blind, Placebo-Controlled Clinical Trial.Advances in therapy · 2023Trial
- Trial
- Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trial.BMJ (Clinical research ed.) · 2022Trial
- Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial.JAMA network open · 2022Trial
- No influence of spironolactone on plasma concentrations of angiotensin-converting enzyme 2: Findings from the HOMAGE randomized trial.Archives of cardiovascular diseases · 2021Trial
- Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial.The Lancet. Respiratory medicine · 2021Trial
- Previous COVID-19 infection: An overlooked cardiovascular risk factor.Journal of human hypertension · 2026Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
33 authors at 15 institutions in 7 countries.
Funding
Abstract
backgroundBiological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.
methodsThe REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009.
findingsBetween March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m
interpretationConsistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19.
fundingREPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.