key: cord-0787581-0qwy46o6
authors: Mancia, Giuseppe
title: COVID-19, hypertension, and RAAS blockers: the BRACE-CORONA trial
date: 2020-11-27
journal: Cardiovasc Res
DOI: 10.1093/cvr/cvaa325
sha: edb5393598ae4a4d0e2601f1d0a97b00befd9187
doc_id: 787581
cord_uid: 0qwy46o6

nan

The trial involved 34 Brazilian medical sites which recruited 659 hypertensive patients defined as having a COVID-19 infection of moderate severity and elected to take, as the primary endpoint, the number of days they were alive and out-of-hospital over a 30-day period. The design was open label and the endpoint estimate was blind. As shown in the presentation of the trial at the recent virtual meeting of the European Society of Cardiology, the number of alive and out-of-hospital patients was similar between the two groups, the mean risk ratio being 0.95 (95% confidence interval 0.90-1.01, P = 0.09) with a between-group not significant difference of just 1.1 days. The same was true for the number of patients who died (9 in either group) which exhibited a risk ratio of 0.97 and a 95% confidence interval of 0.38-2.52 (P = 0.95). This justified the conclusion that the results offered no evidence that during a COVID-19 infection ACE inhibitors and angiotensin receptor blockers affect the disease outcome, in line with the previous evidence that this is the case for pretreatment with these drugs as well.

Do the results of the BRACE-CORONA trial provide a final negative answer to the hypothesis of a relationship between RAAS blockers and the SARS-CoV-2 virus? Although the BRACE-CORONA trial was correctly designed and well conducted, the trial has limitations that make confirmatory studies desirable. First, although further data may be made available in the published paper, the presentation did not include ontreatment variables, leaving without answer the possibility for the between-group outcome similarity to be driven by BP or other differences that moved to the null some direct effect of RAAS blockers on the disease severity. Second, rather than assessing the disease severity by death or need of intensive care, the trial made use of an unusual primary endpoint, i.e. patients alive and out-of-hospital, which might have been influenced by differences in dismissal criteria from hospital between medical sites. Third, although the included patients had a high prevalence of factors that are known to increase COVID-19 severity (hypertension: 100%, diabetes: >30%, obesity: >55%), mortality was so low as to prevent any meaningful analysis of an endpoint such as death as well as to use death to reliably back the primary endpoint results. Finally, the study was not planned to separately analyse the effect of ACE inhibitors and angiotensin receptor blockers, despite previous reports that during the COVID-19 infection their effect may differ 10 Because the number of patients under ACE inhibitors was much greater than that of patients under angiotensin receptor blockers, it seems unlikely that this question will be convincingly addressed by subgroup analysis. The above criticism does not detract from the importance and interest of the results of the BRACE-CORONA trial which deserves the praise of the medical community for providing the first controlled data in an area where so far only observational studies, with their well-known limitations, have been made available. Hopefully, this will serve as a stimulus for future controlled trials aiming at expanding on the BRACE-CORONA evidence to be designed and implemented.

Conflict of interest: none declared.

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He is an honorary member of several hypertension and cardiovascular societies and has received, for his scientific activity, many international Awards and degrees Honoris Causa. He is the Editor-in-Chief of the Journal of Hypertension. Professor Mancia's research focuses on several basic and clinical aspects of hypertension and cardiovascular disease

COVID-19, hypertension, and RAAS blockers