Open AccessAngiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease
Author(s) -
Sebastian Cremer,
Lisa Pilgram,
Alexander Berkowitsch,
Melanie Stecher,
Siegbert Rieg,
Mariana Shumliakivska,
Denisa Bojkova,
Jasmin Wagner,
Galip Servet Aslan,
Christoph D. Spinner,
Guillermo Luxán,
Frank Hanses,
Sebastian Dolff,
Christiane Piepel,
Clemens Ruppert,
Andreas Guenther,
Maria Madeleine Rüthrich,
Jörg Janne Vehreschild,
Kai Wille,
Martina Haselberger,
Hanno Heuzeroth,
Arne Hansen,
Thomas Eschenhagen,
Jindrich Cinatl,
Sandra Ciesek,
Stefanie Dimmeler,
Stefan Borgmann,
Andreas M. Zeiher
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0258684
Subject(s) - medicine , angiotensin receptor , angiotensin ii , angiotensin converting enzyme 2 , gastroenterology , angiotensin converting enzyme , procalcitonin , ace inhibitor , comorbidity , renin–angiotensin system , endocrinology , disease , covid-19 , receptor , blood pressure , sepsis , infectious disease (medical specialty)
Aims Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity. Methods and results We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators. Conclusion These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.