The Efficacy of the Mineralcorticoid Receptor Antagonist Canrenone in COVID-19 Patients

Abstract

Background: In COVID-19 patients, aldosterone via angiotensin-converting enzyme-2 deregulation may be responsible for systemic and pulmonary vasoconstriction, inflammation, and oxidative organ damage. Aim: To verify retrospectively the impact of the mineralcorticoid receptor antagonist canrenone i.v. on the need of invasive ventilatory support and/or all-cause in-hospital mortality. Methods: Sixty-nine consecutive COVID-19 patients, hospitalized for moderate to severe respiratory failure at Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico of Milan, received two different therapeutic approaches in usual care according to the personal skills and pharmacological management experience of the referral medical team. Group A (n = 39) were given vasodilator agents or renin–angiotensin–aldosterone system (RAAS) inhibitors and group B (n = 30) were given canrenone i.v. Results: Among the 69 consecutive COVID-19 patients, those not receiving canrenone i.v. (group A) had an event-free rate of 51% and a survival rate of 64%. Group B (given a mean dose of 200 mg/q.d. of canrenone for at least two days of continuous administration) showed an event-free rate of 80% with a survival rate of 87%. Kaplan–Meier analysis for composite outcomes and mortality showed log rank statistics of 0.0004 and 0.0052, respectively. Conclusions: The novelty of our observation relies on the independent positive impact of canrenone on the all-cause mortality and clinical improvement of COVID-19 patients ranging from moderate to severe diseases.

SARS-CoV-2 Spike Protein S1-Mediated Endothelial Injury and Pro-Inflammatory State Is Amplified by Dihydrotestosterone and Prevented by Mineralocorticoid Antagonism

“…Taken together, these data support a rationale for further testing of mineralocorticoid antagonism to attenuate tissue damage in COVID-19 mediated by endothelial injury, particularly in men. Early randomized clinical trials with a small sample size showed beneficial effects of anti-androgen therapy in mild-to-moderate and severe COVID-19 infection by improving the virus clearance, and reducing time to clinical remission [70][71][72]. Well-powered clinical trials are next needed to investigate a potential beneficial effect of mineralocorticoid antagonism to reduce the risk of COVID-19 adverse outcomes such as organ dysfunction, hospitalization and mortality.…”

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

“…Increased plasma aldosterone levels associated with disease severity in COVID-19 patients ( Villard et al, 2020 ) suggest that MRBs may have beneficial effects in COVID-19. A recent study concluded that canrenone decreased all-cause mortality and improved the clinical outcome in a small cohort of 30 COVID-19 patients with diseases ranging from moderate to severe (M. Vicenzi et al, 2020 ). Another diuretic, furosemide, significantly decreased lipopolysaccharide-induced proinflammatory cytokine production in cell lines and potently inhibited IL-6 and TNF-α release ( Z. Wang, Y. Wang, et al, 2020 ), suggesting its potential use in hypercytokinemic conditions in COVID-19.…”

Follow Your Nose: A Key Clue to Understanding and Treating COVID-19

“…Vicenzi et al. ( 32 ) gave canrenone intravenously to COVID-19 patients admitted to hospital with moderate to severe respiratory failure. Canrenone is a metabolite of spironolactone and has the advantage that it can be given intravenously.…”