Chronic use of Renin‐Angiotensin‐Aldosterone‐System blockers and mortality in COVID‐19: a multicenter prospective cohort and literature review

• Published in: Fundamental & clinical pharmacology 2021-04, Vol.35 (6), p.1141-1158
• Main Authors: Gault, Nathalie, Esposito‐farese, Marina, Revest, Matthieu, Inamo, Jocelyn, Cabie, André, Polard, Élisabeth, Hulot, Jean‐sébastien, Ghosn, Jade, Chirouze, Catherine, Deconinck, Laurène, Diehl, Jean‐luc, Poissy, Julien, Epaulard, Olivier, Lefèvre, Benjamin, Piroth, Lionel, de Montmollin, Etienne, Oziol, Eric, Etienne, Manuel, Laouenan, Cédric, Rossignol, Patrick, Costagliola, Dominique, Vidal‐petiot, Emmanuelle, Andréjak, Claire
• Format: Article
• Language: English
• Subjects: Cardiology and cardiovascular system; Emerging diseases; Human health and pathology; Life Sciences; Santé publique et épidémiologie
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12683

Aims: The role of renin-angiotensin-aldosterone system (RAAS) blockers on the course of coronavirus disease 2019 (COVID-19) is debated. We assessed the association between chronic use of RAAS blockers and mortality among inpatients with COVID-19, and explored reasons for discrepancies in the literature.Methods and results: We included adult hypertensive patients from a prospective nationwide cohort of 3512 inpatients with COVID-19 up to June 30, 2020. Cox proportional hazard models with various adjustment or propensity weighting methods were used to estimate the Hazard Ratios (HR) of 30-day mortality for chronic users versus non-users of RAAS blockers. We analyzed data of 1160 hypertensive patients; 719 (62%) were male, 777 (67%) were older than 65 years. The main comorbidities were diabetes (n=416, 36%), chronic cardiac disease (n=401, 35%) and obesity (n=340, 29%); 705 (61%) received oxygen therapy. We recorded 135 (11.6%) deaths within 30 days of diagnosis. We found no association between chronic use of RAAS blockers and mortality (unadjusted HR=1.13, 95% CI [0.8-1.6]; propensity inverse probability treatment weighted HR=1.09 [0.86-1.39]; propensity standardized mortality ratio weighted HR=1.08 [0.79-1.47]). Our comprehensive review of previous studies highlighted that significant associations were mostly found in unrestricted populations with inappropriate adjustment, or with biased in-hospital exposure measurement.Conclusion: Our results do not support previous concerns regarding these drugs, nor a potential protective effect as reported in previous poorly designed studies and metanalyses. RAAS blockers should not be discontinued during the pandemic, while in-hospital management of these drugs will be clarified by randomized trials. NCT04262921.