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. 2022 Apr 8;158(7):315-323.
doi: 10.1016/j.medcle.2021.04.026. Epub 2022 May 3.

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

Álvaro Aparisi  1 , Pablo Catalá  1 , Ignacio J Amat-Santos  1   2 , Marta Marcos-Mangas  1 , Diego López-Otero  2   3 , Carlos Veras  1 , Javier López-Pais  2   3 , Gonzalo Cabezón-Villalba  1 , Carla Eugenia Cacho Antonio  3 , Jordi Candela  1 , Pablo Antúnez-Muiños  3 , José Francisco Gil  1 , Teba González Ferrero  3 , Gino Rojas  1 , Marta Pérez-Poza  3 , Aitor Uribarri  1   2 , Oscar Otero-García  3 , Pablo Elpidio García-Granja  1   2 , Víctor Jiménez Ramos  3 , Ana Revilla  1   2 , Carlos Dueñas  4 , Itzíar Gómez  1   2 , José Ramón González-Juanatey  2   3 , J Alberto San Román  1   2
Affiliations

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

Álvaro Aparisi et al. Med Clin (Engl Ed). .

Abstract
in English, Spanish

Background: Hypertension is a prevalent condition among SARS-CoV-2 infected patients. Whether renin-angiotensin-aldosterone system (RAAS) inhibitors are beneficial or harmful is controversial.

Methods: We have performed a national retrospective, nonexperimental comparative study from two tertiary hospitals to evaluate the impact of chronic use of RAAS inhibitors in hypertensive COVID-19 patients. A meta-analysis was performed to strengthen our findings.

Results: Of 849 patients, 422 (49.7%) patients were hypertensive and 310 (73.5%) were taking RAAS inhibitors at baseline. Hypertensive patients were older, had more comorbidities, and a greater incidence of respiratory failure (-0.151 [95% CI -0.218, -0.084]). Overall mortality in hypertensive patients was 28.4%, but smaller among those with prescribed RAAS inhibitors before (-0.167 [95% CI -0.220, -0.114]) and during hospitalization (0.090 [-0.008,0.188]). Similar findings were observed after two propensity score matches that evaluated the benefit of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among hypertensive patients. Multivariate logistic regression analysis of hypertensive patients found that age, diabetes mellitus, C-reactive protein, and renal failure were independently associated with all-cause mortality. On the contrary, ACEIs decreased the risk of death (OR 0.444 [95% CI 0.224-0.881]). Meta-analysis suggested a protective benefit of RAAS inhibitors (OR 0.6 [95% CI 0.42-0.8]) among hypertensive COVID-19.

Conclusion: Our data suggest that RAAS inhibitors may play a protective role in hypertensive COVID-19 patients. This finding was supported by a meta-analysis of the current evidence. Maintaining these medications during hospital stay may not negatively affect COVID-19 outcomes.

Introducción: La hipertensión es una condición prevalente entre los pacientes infectados por el SARS-CoV-2. Es controvertido si los inhibidores del sistema renina-angiotensina-aldosterona (SRAA) son beneficiosos o perjudiciales.

Métodos: Hemos desarrollado un estudio comparativo nacional retrospectivo y no experimental en 2 hospitales terciarios para evaluar el impacto del uso crónico de inhibidores del SRAA en pacientes hipertensos con COVID-19. Se realizó un metaanálisis para reforzar los hallazgos.

Resultados: De 849 pacientes, 422 (49,7%) eran hipertensos y 310 (73,5%) tomaban inhibidores del SRAA al inicio del estudio. Los pacientes hipertensos eran mayores, tenían más comorbilidades y una mayor incidencia de insuficiencia respiratoria (−0,151; IC 95%: [−0,218; −0,084]). La mortalidad global en los pacientes hipertensos fue del 28,4%, pero fue menor entre los que tenían prescritos inhibidores del SRAA antes (−0,167; IC 95%: [−0,220; −0,114]) y durante la hospitalización (0,090; [−0,008; 0,188]). Se observaron hallazgos similares tras 2 emparejamientos de puntuación de propensión que evaluaron el beneficio de los inhibidores de la enzima convertidora de angiotensina y los bloqueadores de los receptores de angiotensina entre los pacientes hipertensos. El análisis de regresión logística multivariante de los pacientes hipertensos reveló que la edad, la diabetes mellitus, la proteína C reactiva y la insuficiencia renal se asociaban de forma independiente con la mortalidad por todas las causas. Por el contrario, los inhibidores de la enzima convertidora de angiotensina disminuyeron el riesgo de muerte (OR 0,444; IC 95%: 0,224-0,881). El metaanálisis indicó un beneficio protector de los inhibidores del SRAA (OR 0,6; IC 95%: 0,42-0,8) entre los hipertensos con COVID-19.

Conclusión: Nuestros datos indican que los inhibidores del SRAA pueden desempeñar un papel protector en los pacientes hipertensos con COVID-19. Este hallazgo fue apoyado por un metaanálisis de la evidencia actual. Su mantenimiento durante la estancia hospitalaria puede no afectar negativamente a los resultados de la COVID-19.

Keywords: Angiotensin II receptor blockers; Angiotensin-converting-enzyme inhibitors; COVID-19; Hypertension; Meta-analysis; SARS-CoV-2.

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Figures

Fig. 1
Fig. 1
Forrest plot of showing the Odds Ratio (OR) of the main outcomes: (A) All-cause mortality; (B) Mechanical ventilation; and (C) Intensive care unit admission. *Vertical line represents “no difference” point between hypertensive COVID-19 patients with chronic RAAS vs. Non-RAAS inhibitors treatment; Horizontal lines 95% confidence interval (CI). Squares represent the odds ratio for each study (the size of each square denotes the proportion of information given by each study); Diamonds represent pooled odds ratios from all studies.
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