Can Isosorbide Dinitrate Save Lives of Hospitalized COVID Patients with Hypertension and a Defined Cardiac Injury?
This is the title of the poster abstract that was presented at the 2021 American Heart Association Scientific Sessions virtual meeting last month with the support of CERVOE.org. A successful randomized clinical trial would demonstrate that isosorbide dinitrate can help this cohort of COVID patients that have a very high mortality. It would also add to the evidence that isosorbide dinitrate has anti-viral properties by inactivation of the SARS-CoV-2 main protease (Mpro). S-nitrosylation of cysteine 145 in the active catalytic site is the posited mechanism of action.
The abstract for poster@9991 can be found at:
https://www.ahajournals.org/doi/abs/10.1161/circ.144.suppl_1.9991
Any citation should read: Roesel, T. Can Isosorbide Dinitrate Save Lives in Hospitalized COVID-19 Patients with Hypertension and a Defined Cardiac Injury? Circulation. 2021;144 (supplement):A9991
A copy of the abstract and figure as it appears in the above reference follows:
Abstract 9991: Can Isosorbide Dinitrate Save Lives of Hospitalized COVID Patients with Hypertension and a Defined Cardiac Injury?
Originally published 8 Nov 2021Circulation. 2021;144:A9991
Abstract
Introduction: As defined by MB-CPK, hsTn-I, MB, or EKG and/or cardiac echo abnormalities, cardiac injury (CI) determines a median survival time (MST) of 10 days for hospitalized COVID patients (HCPs). HCPs without defined CI have an MST beyond 39 days (Huang, et al., see Figure). Hypertension (HTN) presents in 17-41% of HCPs in various studies, with COVID mortality independent of HTN. Therefore, a randomized clinical trial (RCT) is proposed for HCPs with CI and incidental BP elevation to compare IV isosorbide dinitrate (ISDN) with usual anti-HTN care (UC). Vasodilatory ISDN lowers BP, and has been proposed as an anti-SARS-CoV-2 drug. Others report improved survival of ISDN treated Coxsackie B3 virus-infected mice as evidence for anti-viral activity. The endpoint for this CI RCT pilot of 100 ISDN-treat HCPs and 100 UC controls is mortality. Secondary endpoints are interval biomarkers to dissect ISDN anti-viral action.
Methods: Log-rank analysis was performed with 1:1 allocation. Accrual time was 180 days with a 60-day follow-up. Power was 0.8 with a type I error of 0.05.
Results: For 200 total subjects, an MST greater than 14.9 days in the ISDN arm was significant if UC stays at 10 days (see Figure).
Conclusions: Testing repurposed ISDN as a COVID drug is feasible. A successful pilot with improved MST suggests ISDN has anti-SARS-CoV-2 action, since COVID mortality is independent of HTN. Biomarkers could include viral clearance, oxygenation, D-dimer, IL-6, LDH, as well as platelet and lymphocyte counts. The need to treat HCPs with elevated BP per guidelines permits study entry. Cross-over treatment occurs if a regimen fails. Immunomodulators and remdesivir are administered per COVID treatment guidelines for all HCPs. IV ISDN, bolused and/or infused, avoids 1st pass hepatic effects. IV IDSN is approved in most countries, but not in the USA or Canada. A successful pilot would permit larger IV ISDN RCTs as IND RCTs, and can serve as a template for other treatments for HCPs with defined CI.
