{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T06:14:50Z","timestamp":1783145690805,"version":"3.54.6"},"reference-count":20,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010340","name":"Lebanese American University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010340","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Coronavirus disease 2019 (COVID\u201019) is associated with endothelial dysfunction. Pharmacologically targeting the different mechanisms of endothelial dysfunction may improve clinical outcomes and lead to reduced morbidity and mortality. In this pilot, double\u2010blind, placebo\u2010controlled, randomized clinical trial, we assigned patients who were admitted to the hospital with mild, moderate, or severe COVID\u201019 infection to receive, on top of optimal medical therapy, either an endothelial protocol consisting of (Nicorandil, L\u2010arginine, folate, Nebivolol, and atorvastatin) or placebo for up to 14\u2009days. The primary outcome was time to recovery, measured by an eight category ordinal scale and defined by the time to being discharged from the hospital or hospitalized for infection\u2010control or other nonmedical reasons. Secondary outcomes included the composite outcome of intensive care unit (ICU) admission or the need for mechanical ventilation, all\u2010cause mortality, and the occurrence of side effects. Of 42 randomized patients, 37 were included in the primary analysis. The mean age of the patients was 57\u2009years; the mean body mass index of study participants was 29.14. History of hypertension was present in 27% of the patients, obesity in 45%, and diabetes mellitus in 21.6%. The median (interquartile range) time to recovery was not significantly different between the endothelial protocol group (6 [4\u201312] days) and the placebo group (6 [5\u20138] days;\n                    <jats:italic>p<\/jats:italic>\n                    value\u00a0=\u00a00.854). Furthermore, there were no statistically significant differences in the need for mechanical ventilation or ICU admission, all\u2010cause mortality, or the occurrence of side effects between the endothelial protocol group and the placebo group. Among patients hospitalized with mild, moderate, or severe COVID\u201019 infection, targeting endothelial dysfunction by administering Nicorandil, L\u2010arginine, Folate, Nebivolol, and Atorvastatin on top of optimal medical therapy did not decrease time to recovery. Based on this study\u2019s findings, targeting endothelial dysfunction did not result in a clinically significant improvement in outcome and, as such, larger trials targeting this pathway are not recommended.\n                  <\/jats:p>","DOI":"10.1111\/cts.13369","type":"journal-article","created":{"date-parts":[[2022,7,9]],"date-time":"2022-07-09T01:58:52Z","timestamp":1657331932000},"page":"2323-2330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Managing endothelial dysfunction in\n                    <scp>COVID<\/scp>\n                    \u201019 with statins, beta blockers, nicorandil, and oral supplements: A\u00a0pilot,\n                    <scp>double\u2010blind<\/scp>\n                    ,\n                    <scp>placebo\u2010controlled<\/scp>\n                    , randomized clinical trial"],"prefix":"10.1111","volume":"15","author":[{"given":"Kamal","family":"Matli","sequence":"first","affiliation":[{"name":"Cardiology Department Lebanese American University Medical Center \u2013 Rizk Hospital  Beirut Lebanon"},{"name":"Service de Cardiologie Centre Hospitalier de Haguenau  Haguenau France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Al Kotob","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Lebanese American University Medical Center \u2013 Rizk Hospital  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5678-5260","authenticated-orcid":false,"given":"Wassim","family":"Jamaleddine","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Lebanese American University Medical Center \u2013 Rizk Hospital  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soad","family":"Al Osta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Lebanese American University Medical Center \u2013 Rizk Hospital  Beirut Lebanon"},{"name":"School of Medicine, Lebanese American University  Byblos Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Salameh","sequence":"additional","affiliation":[{"name":"School of Medicine, Lebanese American University  Byblos Lebanon"},{"name":"Faculty of Pharmacy Lebanese University  Hadat Lebanon"},{"name":"Institut National de Sant\u00e9 Publique d'Epid\u00e9miologie Clinique et Toxicologie \u2013 Liban (INSPECT\u2010LB)  Beirut Lebanon"},{"name":"Department of Primary Care and Population Health University of Nicosia Medical School  Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Tabbikha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Lebanese American University Medical Center \u2013 Rizk Hospital  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nibal","family":"Chamoun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice Lebanese American University School of Pharmacy  Byblos Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Moussawi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Lebanese American University Medical Center \u2013 Rizk Hospital  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Michel","family":"Saad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Lebanese American University Medical Center \u2013 Rizk Hospital  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gibran","family":"Atwi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Lebanese American University Medical Center \u2013 Rizk 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