Chronic use of renin–angiotensin–aldosterone inhibitors in hypertensive COVID-19 patients: Results from a Spanish registry and meta-analysis

Alonso, Álvaro; Catalá, Pablo; Amat‐Santos, Ignacio J.; Marcos-Mangas, Marta; López-Otero, Diego; Veras, Carlos; López-País, Javier; Cabezón-Villalba, Gonzalo; Cacho-Antonio, Carla; Candela, Jordi; Antúnez-Muiños, Pablo; Gil, José Francisco López; Ferrero, T Gonzalez; Rojas, Gino; Pérez-Poza, Marta; Uribarri, Aitor; García, O. Otero; García‐Granja, Pablo Elpidio; Ramos, Vítor; Revilla, Ana; Dueñas, Carlos; Gómez, Itzíar; González-Juanàtey, José Ramón; Román, José Alberto San

doi:10.1016/j.medcli.2021.04.005

Cited by 13 publications

(7 citation statements)

References 30 publications

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“…The systematic search identified 169 observational studies that assessed the associations between RAAS inhibitor use and the risk of contracting a SARS‐CoV‐2 infection and/or experiencing severe COVID‐19 outcomes (Figure 1 ). 8 , 19 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , …”

Section: Resultsmentioning

confidence: 99%

“…This study was not the first systematic review and meta‐analysis to assess the associations between RAAS inhibitor use and COVID‐19 outcomes. As of December 2021, at least 52 meta‐analyses had been conducted, 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 each of which pooled studies that have a critical risk of bias. Critical biases limit confidence in the evidence produced by these meta‐analyses as much as they do in each of the studies that t...…”

Section: Discussionmentioning

confidence: 99%

“… 6 At least 52 meta‐analyses have assessed associations between RAAS inhibitor use and COVID‐19 risk by collating parts of that body of research. 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 However, little attention has been paid to selection bias, or other biases for that matter, which may distort the interaction between RAAS inhibitor use and COVID‐19.…”

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confidence: 99%

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Renin‐Angiotensin Aldosterone System Inhibitors and COVID‐19: A Systematic Review and Meta‐Analysis Revealing Critical Bias Across a Body of Observational Research

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Lampa

et al. 2022

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Background Renin‐angiotensin aldosterone system (RAAS) inhibitor—COVID‐19 studies, observational in design, appear to use biased methods that can distort the interaction between RAAS inhibitor use and COVID‐19 risk. This study assessed the extent of bias in that research and reevaluated RAAS inhibitor—COVID‐19 associations in studies without critical risk of bias. Methods and Results Searches were performed in MEDLINE, EMBASE, and CINAHL databases (December 1, 2019 to October 21, 2021) identifying studies that compared the risk of infection and/or severe COVID‐19 outcomes between those using or not using RAAS inhibitors (ie, angiotensin‐converting enzyme inhibitors or angiotensin II type‐I receptor blockers). Weighted hazard ratios (HR) and 95% CIs were extracted and pooled in fixed‐effects meta‐analyses, only from studies without critical risk of bias that assessed severe COVID‐19 outcomes. Of 169 relevant studies, 164 had critical risks of bias and were excluded. Ultimately, only two studies presented data relevant to the meta‐analysis. In 1 351 633 people with uncomplicated hypertension using a RAAS inhibitor, calcium channel blocker, or thiazide diuretic in monotherapy, the risk of hospitalization (angiotensin‐converting enzyme inhibitor: HR, 0.76; 95% CI, 0.66–0.87; P <0.001; angiotensin II type‐I receptor blockers: HR, 0.86; 95% CI, 0.77–0.97; P =0.015) and intubation or death (angiotensin‐converting enzyme inhibitor: HR, 0.64; 95% CI, 0.48–0.85; P =0.002; angiotensin II type‐I receptor blockers: HR, 0.74; 95% CI, 0.58–0.95; P =0.019) with COVID‐19 was lower in those using a RAAS inhibitor. However, these protective effects are probably not clinically relevant. Conclusions This study reveals the critical risk of bias that exists across almost an entire body of COVID‐19 research, raising an important question: Were research methods and/or peer‐review processes temporarily weakened during the surge of COVID‐19 research or is this lack of rigor a systemic problem that also exists outside pandemic‐based research? Registration URL: www.crd.york.ac.uk/prospero/ ; Unique identifier: CRD42021237859.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Renin‐Angiotensin Aldosterone System Inhibitors and COVID‐19: A Systematic Review and Meta‐Analysis Revealing Critical Bias Across a Body of Observational Research

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Lampa

et al. 2022

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“…Five studies were performed in single centers and six in multiple centers. The studies were distributed across several countries, including Canada [ 37 ], United States [ 31 , 32 ], Spain [ 35 , 36 ], Italy [ 30 ], Brazil [ 40 ], Iran [ 33 ], France [ 34 ], Austria, and Germany [ 38 ]. One study simultaneously covered several American countries and Sweden [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

“…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]. In total, 2823 hospitalized patients were recruited in the eleven studies.…”

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

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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

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Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient

García-Álvarez,

Zapata-Cachafeiro,

Visos-Varela

et al. 2024

Inflammopharmacol

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Objectives To assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19. Methods We conducted a multiple population-based case–control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated. Results ACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69–0.89] and aOR = 0.80 [95%CI 0.72–0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52–0.98] and aOR = 0.69 [95%CI 0.52–0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82–0.94] and aOR = 0.92 [95%CI 0.86–0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61–0.85]), mortality (aOR = 0.59 [95%CI 0.38–0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79–0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60–0.95]), mortality (aOR = 0.36 [95%CI 0.17–0.75]) and disease progression (aOR = 0.73 [95%CI 0.56–0.95]). Conclusion This large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes.

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Chronic use of renin–angiotensin–aldosterone inhibitors in hypertensive COVID-19 patients: Results from a Spanish registry and meta-analysis

Cited by 13 publications

References 30 publications

Renin‐Angiotensin Aldosterone System Inhibitors and COVID‐19: A Systematic Review and Meta‐Analysis Revealing Critical Bias Across a Body of Observational Research

Renin‐Angiotensin Aldosterone System Inhibitors and COVID‐19: A Systematic Review and Meta‐Analysis Revealing Critical Bias Across a Body of Observational Research

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

Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient

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