key: cord-1007722-oaray2x6 authors: Jung, Christian; Bruno, Raphael Romano; Wernly, Bernhard; Joannidis, Michael; Oeyen, Sandra; Zafeiridis, Tilemachos; Marsh, Brian; Andersen, Finn H; Moreno, Rui; Fernandes, Ana Margarida; Artigas, Antonio; Pinto, Bernardo Bollen; Schefold, Joerg; Wolff, Georg; Kelm, Malte; De Lange, Dylan W; Guidet, Bertrand; Flaatten, Hans; Fjølner, Jesper title: Inhibitors of the renin–angiotensin–aldosterone system and COVID-19 in critically ill elderly patients date: 2020-07-09 journal: Eur Heart J Cardiovasc Pharmacother DOI: 10.1093/ehjcvp/pvaa083 sha: a26449ce9faa581c3b67de341848c3cc9de27094 doc_id: 1007722 cord_uid: oaray2x6 nan patients, who represent the most vulnerable group of patients affected by COVID-19 and are also most likely treated with RAAS inhibitors within the general population. To investigate special clinical features in COVID-19, the COVIP study (Very old intensive care patients, VIP network; NCT04321265) is ongoing. COVIP prospectively includes patients equal to or above 70 years of age with proven COVID-19 who are admitted to an intensive care unit (ICU). A total of 244 ICUs in 38 countries are registered to participate in COVIP. The primary endpoint is death after 30 days. Inclusion criteria are (i) age > _70 years, (ii) ICU admission, and (iii) infection with SARS-CoV-2. Furthermore, a follow-up will be performed after 3 months to assess death and quality of life. The prospective design aims to create high-quality data about risk factors, comorbidities, pre-existing frailty, ICU-treatment including treatment limitations, and the use of experimental drugs in this critically ill patient collective of elderly patients. An interim analysis was performed on 7th of May with respect to RAAS inhibitor use. In total, 324 patients were evaluated ( Table 1) : 157 (48%) were on RAAS inhibitors, 62 (19%) on angiotensin-converting enzyme inhibitors (ACE-I), and 95 (29%) on angiotensin II receptor blockers (ARB) before disease onset. Overall ICU mortality was 45% and was similar between patients with and without previous ARB (45% vs. 45%; P = 0.98), but lower in patients with previous ACE-I (31% vs. 49%; P = 0.01). A propensity for being on ACE-I was calculated using logistic regression, the covariates were age, body mass index, sex, sequential organ failure assessment (SOFA) score, as well as existing comorbidities of chronic heart failure, ischaemic heart disease, renal insufficiency, chronic pulmonary disease, arterial hypertension, and diabetes mellitus ( Table 1 ). The primary endpoint was ICU mortality. Both univariable (Model 1) and multivariable (Model 2, propensity score correction) logistic regression models were built to evaluate associations with the primary endpoint. Odds ratios (OR, Model 1, Table 1 ) and adjusted ORs (aOR, Model 2) with respective 95% confidence intervals (CIs) were calculated. The univariate association of previous ACE-I with lower mortality (OR 0.46, 95% CI 0.26-0.84; P = 0.01; Table 1 ) remained statistically significant after propensity score adjustment (aOR 0.32, 95% CI 0.15-0.67; P = 0.002). In conclusion, in a prospective study of elderly, critically ill and comorbid patients, we do find a beneficial association of previous ACE-I use with ICU survival. The current data confirms the notion that there is either a positive or no effect of RAAS inhibitor use. In addition, our data support the current view that continuation of RAAS inhibitor use should be recommended. 4 In summary, this is the first prospective multinational study that demonstrates beneficial associations of ACE-I in highrisk COVID-19 patients and thus impact on daily practice. However, further research evaluating potential causality is warranted. Association of use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with testing positive for coronavirus disease 2019 (COVID-19) Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19 Renin-angiotensin-aldosterone system blockers and the risk of Covid-19 Renin-angiotensin system blockers and the COVID-19 pandemic The support of the study in France by Assistance Publique-Hôpitaux de Paris is greatly appreciated. Trial registration number: NCT043 21265.Conflict of interest: none declared.