Discontinuing vs continuing ACEIs and ARBs in hospitalized patients with COVID-19 according to disease severity: Insights from the BRACE CORONA trial

Macedo, Ariane Vieira Scarlatelli; Silva, Pedro Gabriel Melo de Barros e; Paula, Thiago Ceccatto de; Moll-Bernardes, Renata; Santos, Tiago Mendonça dos; Mazza, Lilian; Feldman, André; Arruda, Guilherme D’Andréa Saba; Albuquerque, Denílson Campos de; Sousa, Andréa Silvestre de; Souza, Olga Ferreira de; Gibson, C. Michael; Granger, Christopher B.; Alexander, John H.; Lópes, Renato D.

doi:10.1016/j.ahj.2022.04.001

Cited by 9 publications

(6 citation statements)

References 30 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thereafter, 2160 were excluded based on their titles and abstracts. Further full text evaluation eliminated 65 studies, including one study that reported overlapping data from a different perspective [29]. Finally, we included 11 studies, including seven observational studies [30][31][32][33][34][35][36] and four RCTs [37][38][39][40].…”

Section: Resultsmentioning

confidence: 99%

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

Liu

Zhu

et al. 2023

BMC Infect Dis

View full text Add to dashboard Cite

Background The effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on mortality was preliminarily explored through the comparison of ACEIs/ARBs with non-ACEIs/ARBs in patients with coronavirus disease 2019 (COVID-19). Reaching a conclusion on whether previous ACEI/ARB treatment should be continued in view of the different ACE2 levels in the comparison groups was not unimpeachable. Therefore, this study aimed to further elucidate the effect of ACEI/ARB continuation on hospital mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) in the same patient population. Methods We searched PubMed, the Cochrane Library, Ovid, and Embase for relevant articles published between December 1, 2019 and April 30, 2022. Continuation of ACEI/ARB use after hospitalization due to COVID-19 was considered as an exposure and discontinuation of ACEI/ARB considered as a control. The primary outcome was hospital mortality, and the secondary outcomes included 30-day mortality, rate of ICU admission, IMV, and other clinical outcomes. Results Seven observational studies and four randomized controlled trials involving 2823 patients were included. The pooled hospital mortality in the continuation group (13.04%, 158/1212) was significantly lower than that (22.15%, 278/1255) in the discontinuation group (risk ratio [RR] = 0.45; 95% confidence interval [CI], 0.28–0.72; P = 0.001). Continuation of ACEI/ARB use was associated with lower rates of ICU admission (10.5% versus 16.2%, RR = 0.63; 95% CI 0.5–0.79; P < 0.0001) and IMV (8.2% versus 12.5%, RR = 0.62; 95% CI 0.46–0.83, P = 0.001). Nevertheless, the effect was mainly demonstrated in the observational study subgroup (P < 0.05). Continuing ACEI/ARB had no significant effect on 30-day mortality (P = 0.34), acute myocardial infarction (P = 0.08), heart failure (P = 0.82), and acute kidney injury after hospitalization (P = 0.98). Conclusion Previous ACEI/ARB treatment could be continued since it was associated with lower hospital deaths, ICU admission, and IMV in patients with COVID-19, although the benefits of continuing use were mainly shown in observational studies. More evidence from multicenter RCTs are still needed to increase the robustness of the data. Trial registration PROSPERO (CRD42022341169). Registered 27 June 2022

show abstract

Section: Resultsmentioning

confidence: 99%

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

Liu

Zhu

et al. 2023

BMC Infect Dis

View full text Add to dashboard Cite

show abstract

“…Moreover, the RCT's participants were all from Brazil and hence extending the findings to other races or ethnicities will be limited; this is particularly important because there are evidence demonstrating that there are potential genetic variants of renin, angiotensinogen, ACE, angiotensin II and ACE2 among various populations that influence the function of the renin–angiotensin–aldosterone system, hence affecting someone’s response to the COVID‐19 infection 72 . On the contrary, another more recent RCT 73 exploring the effect of ACEIs/ARBs discontinuation vs. their continuation among 659 patients found that continuing ACEIs/ARBs in comparison with their discontinuation resulted in lower rates of in‐hospital and 30‐day mortality, hospitalisation stay and COVID‐19 disease progression; however, this positive effect was only seen among those with moderate COVID‐19 at baseline and not those with mild COVID‐19, suggesting that ACEIs/ARBs should be continued in patients with moderate COVID‐19 disease severity, especially as ACEIs/ARBs are well known to have substantial benefits for patients with hypertension and heart failure and thus stopping them would be deleterious; it is worth noting that because about 80% of patients were on ARBs, the observed benefits might not be extended to ACEIs.…”

Section: Discussionmentioning

confidence: 99%

An umbrella review and meta‐analysis of renin–angiotensin system drugs use and COVID‐19 outcomes

Kurdi

Mueller

Weir

2022

Eur J Clin Investigation

View full text Add to dashboard Cite

Background: Despite the availability of extensive literature on the effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) on COVID-19 outcomes, the evidence is still controversial. We aimed to provide a comprehensive assessment of the effect of ACEIs/ARBs on COVID-19-related outcomes by summarising the currently available evidence.Methods: An umbrella review was conducted using Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 1 February 2021.Systematic reviews with meta-analysis that evaluated the effect of ACEIs/ARBs on COVID-19-related clinical outcomes were eligible. Studies' quality was appraised using the AMSTAR 2 Critical Appraisal Tool. Data were analysed using the random-effects modelling including several subgroup analyses. Heterogenicity was assessed using I 2 statistic. The study protocol was registered in PROSPERO (CRD42021233398) and reported using PRISMA guidelines.Results: Overall, 47 reviews were eligible for inclusion. Out of the nine COVID-19 outcomes evaluated, there was significant associations between ACEIs/ARBs use and each of death (OR = 0.80, 95%CI = 0.75-0.86; I 2 = 51.9%), death/ICU admission as composite outcome (OR = 0.86, 95%CI = 0.80-0.92; I 2 = 43.9%), severe COVID-19 (OR = 0.86, 95%CI = 0.78-0.95; I 2 = 68%) and hospitalisation (OR = 1.23, 95%CI = 1.04-1.46; I 2 = 76.4%). The significant reduction in death/ ICU admission, however, was higher among studies which presented adjusted measure of effects (OR = 0.63, 95%CI = 0.47-0.84) and were of moderate quality (OR = 0.74, 95%CI = 0.63-0.85). Conclusions:Collective evidence from observational studies indicate a good quality evidence on the significant association between ACEIs/ARBs use and reduction in death and death/ICU admission, but poor-quality evidence on both reducing severe COVID-19 and increasing hospitalisation. Our findings further support the current recommendations of not discontinuing ACEIs/ARBs therapy in patients with COVID-19.

show abstract

“…In the Blockers of Angiotensin Receptor and Angiotensin-Converting Enzyme inhibitors suspension in hospitalized patients with coronavirus infection (BRACE CORONA) study, the largest investigator-initiated, multicenter, registry-based randomized trial that completed in July 2020, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue (334 patients) vs. continue RAS inhibitors (325 patients) among 659 patients hospitalized with mild to moderate COVID-19 and who were taking these medications before hospital admission [61]. In a subgroup analysis according to disease severity, patients with a moderate severity who continued RAS inhibitors had more days alive and out of hospital through 30 days than those who discontinued these drugs [62]. Both in the Randomized Elimination or ProLongation of ACEIs and ARBs in COr-onaVIrus Disease 2019 (REPLACE COVID) trial, a prospective, randomized, open-label trial done at 20 large referral hospitals in seven countries worldwide [63], and the Stopping ACE-inhibitors in Covid-19 (ACEI-COVID) trial, a multicenter, randomized, controlled, open-label trial [64], discontinuation of RAS inhibitors did not significantly affect the severity of COVID-19 and the primary outcome measure of these studies.…”

Section: Current Evidence On Ace Inhibitors and Arbs In Patients With...mentioning

confidence: 99%

COVID-19 pandemic and hypertension: an updated report from the Japanese Society of Hypertension project team on COVID-19

et al. 2022

View full text Add to dashboard Cite

The number of reported cases with coronavirus disease 2019 (COVID-19) has exceeded 620 million worldwide, still having a profound impact on people's health and daily lives since its occurrence and outbreak in December 2019. From the early phase of the COVID-19 pandemic, there has been a concern that the rapid spread of this communicable disease can negatively influence non-communicable diseases. Accumulating data indicate that the restriction on the access to medical care, psychological distress, and life-style changes triggered by the pandemic have indeed affected blood pressure control in hypertensive patients. Since our previous report in 2020 that summarized the findings of the literature related to COVID-19 and hypertension, there has been a considerable progress in our understanding of the association between these two disorders; nonetheless, there are remaining challenges and emerging questions in the field. In this article, we aim to summarize the latest information on the impact of the pandemic on blood pressure control, the use of the renin-angiotensin system inhibitors in patients with COVID-19, and the blood pressure changes as one of the possible post-acute sequelae of COVID-19 (also known as long COVID). We also summarize the evidence of telemedicine and COVID-19 vaccination in hypertensive subjects, based on data available as of June 2022.

show abstract

Discontinuing vs continuing ACEIs and ARBs in hospitalized patients with COVID-19 according to disease severity: Insights from the BRACE CORONA trial

Cited by 9 publications

References 30 publications

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

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

An umbrella review and meta‐analysis of renin–angiotensin system drugs use and COVID‐19 outcomes

COVID-19 pandemic and hypertension: an updated report from the Japanese Society of Hypertension project team on COVID-19

Contact Info

Product

Resources

About