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. 2021 Feb 16;11(2):e043625.
doi: 10.1136/bmjopen-2020-043625.

Prospective meta-analysis protocol on randomised trials of renin-angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension

Sonali Rukshana Gnanenthiran  1 , Claudio Borghi  2 , Dylan Burger  3 , Fadi Charchar  4 , Neil R Poulter  5 , Markus P Schlaich  6 , Ulrike Muscha Steckelings  7 , George Stergiou  8 , Maciej Tomaszewski  9 , Thomas Unger  10 , Richard D Wainford  11 , Bryan Williams  12 , Anthony Rodgers  1 , Aletta E Schutte  13
Affiliations

Prospective meta-analysis protocol on randomised trials of renin-angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension

Sonali Rukshana Gnanenthiran et al. BMJ Open. .

Abstract

Introduction: Whether ACE inhibitors (ACEi) or angiotensin II receptor blocker (ARB) therapy should be continued, initiated or ceased in patients with COVID-19 is uncertain. Given the widespread use of ACEi/ARBs worldwide, guidance on the use of these drugs is urgently needed. This prospective meta-analysis aims to pool data from randomised controlled trials (RCTs) to assess the safety and efficacy of ACEi/ARB therapy in adults infected with SARS-CoV-2.

Methods and analysis: RCTs will be eligible if they compare patients with COVID-19 randomised to ACEi/ARB continuation or commencement versuss no ACEi/ARB therapy; study duration ≥14 days; recruitment completed between March 2020 and May 2021. The primary outcome will be all-cause mortality at ≤30 days. Secondary outcomes will include mechanical ventilation, admission to intensive care or cardiovascular events at short-term follow-up (≤30 days) and all-cause mortality at longer-term follow-up (>1 month). Prespecified subgroup analyses will assess the effect of sex; age; comorbidities; smoking status; ethnicity; country of origin on all-cause mortality. A search of ClinicalTrials.gov has been performed, which will be followed by a formal search of trial registers, preprint servers, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify RCTs that meet inclusion criteria. To date, a search of ClinicalTrials.gov identified 21 potentially eligible trials for this meta-analysis. We will request trial investigators/sponsors to contribute standardised grouped tabular outcome data.

Ethics and dissemination: Ethics approval and informed consent will be the responsibility of the individual RCTs. Dissemination of results will occur by peer-reviewed publication. The results of our analysis can inform public health policy and clinical decision making regarding ACEi/ARB use in patients with COVID-19 on a global scale.

Keywords: COVID-19; cardiology; hypertension.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Flow chart of trial inclusion. ACEi, ACE inhibitors; ARB, angiotensin II receptor blocker; RCTs, randomised controlled trials.
See this image and copyright information in PMC

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