PloS one · 2021
Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.
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Cremer Sebastian, Pilgram Lisa, Berkowitsch Alexander, Stecher Melanie, Rieg Siegbert, Shumliakivska Mariana, Bojkova Denisa, Wagner Julian Uwe Gabriel, Aslan Galip Servet, Spinner Christoph, Luxán Guillermo, Hanses Frank, Dolff Sebastian, Piepel Christiane, Ruppert Clemens, Guenther Andreas, Rüthrich Maria Madeleine, Vehreschild Jörg Janne, Wille Kai, Haselberger Martina, Heuzeroth Hanno, Hansen Arne, Eschenhagen Thomas, Cinatl Jindrich, Ciesek Sandra, Dimmeler Stefanie, Borgmann Stefan, Zeiher Andreas, LEOSS study group
Аннотация
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.
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.