Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on COVID-19 in a western population. CARDIOVID registry

López-Otero, Diego; López-País, Javier; Cacho-Antonio, Carla; Antúnez-Muiños, Pablo; González-Ferrero, Teba; Pérez-Poza, Marta; García, O. Otero; Díaz-Fernández, Brais; Bastos-Fernández, María; Bouzas-Cruz, Noelia; Sanmartín-Pena, Xoan Carlos; Román, Alfonso Varela; Portela‐Romero, Manuel; Valdés-Cuadrado, Luís; Pose‐Reino, Antonio; González-Juanatey, José Ramón

doi:10.1016/j.rec.2020.05.018

Cited by 22 publications

(41 citation statements)

References 24 publications

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“…The characteristics of the shortlisted studies are summarized in Table 1. Among shortlisted studies, 23 studies were from China , nine studies were from Italy [64][65][66][67][68][69][70][71][72], ten studies were from the United States [83][84][85][86][87][88][89][90][91][92], four studies were from South Korea [75][76][77][78], three studies were from France [60][61][62], two studies were from Spain [79,80], one study each was from Belgium [35], Denmark [59], Hong Kong [63], Kuwait [73], Singapore [74], Turkey [81], and the United Kingdom [82]; and one study included data from 38 countries [93]. There were 24 studies that included hypertensive patients exclusively (100%) [36, 38, 39, 43-45, 47, 48, 50-52, 54, 56, 58, 66, 71, 72, 75, 78, 81, 87-89, 91].…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…The comparison of mortality and clinical severity outcomes between ACEI/ARB users and non-ACEI/ARB users with COVID-19 is summarized in [35,40,52,56,59,61,63,66,74,75,78,80,84,89,90,92] provided adjusted estimates for severe/critical disease with the use of an ACEI/ ARB relative to the non-use of an ACEI/ARB. , it was unclear whether the entire included cohort of patients was followed until discharge/death.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…Since Selçuk et al [81] provided mortality estimates with a very wide CI (OR = 3.66; 95% CI 1.11-18.18), we excluded this study from our meta-analysis. In a pooled analysis of the 12 remaining original studies that provided adjusted ORs, with 18,749 COVID-19 patients being analyzed [35,64,66,75,76,78,80,86,88,89,92,93], the use of an ACEI/ARB was significantly associated with lower odds of mortality compared to non-use of an ACEI/ARB ( Fig. 2; pooled OR = 0.73, 95% CI 0.56-0.95).…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…Ten studies [35,40,61,63,66,75,78,89,90,92] were regarded as 'fair', with scores of 4-6 points. Five studies [52,59,74,80,84] were considered 'poor' (i.e., scored less than 4 points) in the quality assessment.…”

Section: Mortality Associated With the Use Of Ras Inhibitors In Covidmentioning

confidence: 99%

“…The main quality issue noticed in 14 studies [35,40,52,59,61,63,66,74,78,80,84,89,90,92] was the comparison of cohorts with inadequate adjustment for confounders that may influence the estimated risk of severe/critical disease associated with the use of ACEIs/ARBs. Another major issue detected during quality assessment in 12 studies [35,52,59,61,66,74,75,78,80,84,90,92] was the inability to ascertain the exposure to ACEIs/ARBs during the course of illness, where the possibility of discontinuation of ACEIs/ARBs upon COVID-19 diagnosis could not be ruled out based on the study design. Similarly, 12 studies [40,52,59,61,63,74,75,78,84,89,90,92] were not able to demonstrate that severe/critical outcome was not present at the start of the study based on their study design.…”

Section: Severe/critical Outcomes Associated With the Use Of Ras Inhimentioning

confidence: 99%

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Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Hasan

Kow

Hadi

et al. 2020

Am J Cardiovasc Drugs

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Introduction The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19). Methods We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients. A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors. Results A total of 59 original studies were included for qualitative synthesis. Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk. Quality assessment of studies revealed that most of the studies included were of fair quality. The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB. Discussion Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.

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Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Section: Mortality Associated With the Use Of Ras Inhibitors In Covidmentioning

confidence: 99%

Section: Severe/critical Outcomes Associated With the Use Of Ras Inhimentioning

confidence: 99%

See 3 more Smart Citations

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Hasan

Kow

Hadi

et al. 2020

Am J Cardiovasc Drugs

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Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19

et al. 2021

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Key Points Question Is the receipt of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) associated with worse clinical outcomes among patients with COVID-19? Findings In this systematic review and meta-analysis of 52 studies that evaluated clinical outcomes among 101 949 total patients with COVID-19 who did and did not receive ACEIs or ARBs, a significantly lower risk of multivariable-adjusted mortality and severe adverse events was found among patients who received ACEIs or ARBs compared with patients who did not. A subgroup analysis of patients with hypertension indicated significant decreases in mortality and severe adverse events among patients receiving ACEIs or ARBs in both unadjusted and adjusted analyses. Meaning The study’s findings suggest that ACEIs and ARBs may be associated with protective benefits for patients with COVID-19 and that patients may continue receiving ACEIs and ARBs for the treatment of any condition without an increased risk of worse outcomes unless specifically advised to avoid them by treating clinicians.

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The Interplay Between the Immune System, the Renin‐Angiotensin‐Aldosterone System (RAAS), and RAAS Inhibitors May Modulate the Outcome of COVID‐19: A Systematic Review

Naveed

Elshafeey

Al‐Ali

et al. 2021

The Journal of Clinical Pharma

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Since the discovery of the severe acute respiratory syndrome coronarvirus 2 (SARS‐CoV‐2) numerous research was undertaken to delineate the various effects of the virus which manifests in many ways all over the body. The association between the SARS‐CoV‐2 invasion mechanism and the RAAS receptors, created many debates about the possible consequences of using RAAS modulating drugs including the ACE inhibitors (ACEi) and the Angiotensin II Receptor Blockers (ARBs) during the pandemic. Many clinical studies were conducted to assess the outcomes of COVID‐19 in patients who use ACEi/ARBs following the arguments claiming to discontinue these drugs as a precautionary measure. While several studies mainly analyzed the outcomes of the disease, this review aimed at comparing specific blood markers in both groups of COVID‐19 patients in order to gain a better insight into the interaction of ACEi/ARBs with the different body functions during the infection. Several databases were searched using a combination of keywords followed by screening and data extraction. Only 28 studies met our inclusion criteria, the majority of which showed no significant difference between the inflammation markers of COVID‐19 patients who used or did not use ACEi/ARBs. Interestingly, six studies reported lower inflammatory markers in COVID‐19 patients who used ACEi/ARBs and ten studies reported better outcomes among the same group. We therefore conclude that the use of ACEi/ARBs may not lead to worse prognosis of COVID‐19 and may even play a protective role against the hyperinflammatory response associated with COVID‐19. This article is protected by copyright. All rights reserved

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Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on COVID-19 in a western population. CARDIOVID registry

Abstract: Please cite this article in press as: Ló pez-Otero D, et al. Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on COVID-19 in a western population. CARDIOVID registry. Rev Esp Cardiol. 2020.

Cited by 22 publications

References 24 publications

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19

The Interplay Between the Immune System, the Renin‐Angiotensin‐Aldosterone System (RAAS), and RAAS Inhibitors May Modulate the Outcome of COVID‐19: A Systematic Review

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