Managing endothelial dysfunction in COVID‐19 with statins, beta blockers, nicorandil, and oral supplements: A pilot, double‐blind, placebo‐controlled, randomized clinical trial
Abstract Coronavirus disease 2019 (COVID‐19) 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‐blind, placebo‐controlled, randomi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-10-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13369 |
| _version_ | 1797986445581877248 |
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| author | Kamal Matli Abdulrahman Al Kotob Wassim Jamaleddine Soad Al Osta Pascale Salameh Rami Tabbikha Nibal Chamoun Ahmad Moussawi Jean‐Michel Saad Gibran Atwi Tarik Abu Saad Omar Jamal Jacques Mokhbat Georges Ghanem |
| author_facet | Kamal Matli Abdulrahman Al Kotob Wassim Jamaleddine Soad Al Osta Pascale Salameh Rami Tabbikha Nibal Chamoun Ahmad Moussawi Jean‐Michel Saad Gibran Atwi Tarik Abu Saad Omar Jamal Jacques Mokhbat Georges Ghanem |
| author_sort | Kamal Matli |
| collection | DOAJ |
| description | Abstract Coronavirus disease 2019 (COVID‐19) 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‐blind, placebo‐controlled, randomized clinical trial, we assigned patients who were admitted to the hospital with mild, moderate, or severe COVID‐19 infection to receive, on top of optimal medical therapy, either an endothelial protocol consisting of (Nicorandil, L‐arginine, folate, Nebivolol, and atorvastatin) or placebo for up to 14 days. 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‐control or other nonmedical reasons. Secondary outcomes included the composite outcome of intensive care unit (ICU) admission or the need for mechanical ventilation, all‐cause 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 years; 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 [4–12] days) and the placebo group (6 [5–8] days; p value = 0.854). Furthermore, there were no statistically significant differences in the need for mechanical ventilation or ICU admission, all‐cause 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‐19 infection, targeting endothelial dysfunction by administering Nicorandil, L‐arginine, Folate, Nebivolol, and Atorvastatin on top of optimal medical therapy did not decrease time to recovery. Based on this study’s 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. |
| first_indexed | 2024-04-11T07:32:50Z |
| format | Article |
| id | doaj.art-3c74f9186d1d406e8609d9036c6b54b4 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-04-11T07:32:50Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-3c74f9186d1d406e8609d9036c6b54b42022-12-22T04:36:49ZengWileyClinical and Translational Science1752-80541752-80622022-10-0115102323233010.1111/cts.13369Managing endothelial dysfunction in COVID‐19 with statins, beta blockers, nicorandil, and oral supplements: A pilot, double‐blind, placebo‐controlled, randomized clinical trialKamal Matli0Abdulrahman Al Kotob1Wassim Jamaleddine2Soad Al Osta3Pascale Salameh4Rami Tabbikha5Nibal Chamoun6Ahmad Moussawi7Jean‐Michel Saad8Gibran Atwi9Tarik Abu Saad10Omar Jamal11Jacques Mokhbat12Georges Ghanem13Cardiology Department Lebanese American University Medical Center – Rizk Hospital Beirut LebanonDepartment of Internal Medicine Lebanese American University Medical Center – Rizk Hospital Beirut LebanonDepartment of Internal Medicine Lebanese American University Medical Center – Rizk Hospital Beirut LebanonDepartment of Internal Medicine Lebanese American University Medical Center – Rizk Hospital Beirut LebanonSchool of Medicine, Lebanese American University Byblos LebanonDepartment of Internal Medicine Lebanese American University Medical Center – Rizk Hospital Beirut LebanonDepartment of Pharmacy Practice Lebanese American University School of Pharmacy Byblos LebanonDepartment of Internal Medicine Lebanese American University Medical Center – Rizk Hospital Beirut LebanonDepartment of Internal Medicine Lebanese American University Medical Center – Rizk Hospital Beirut LebanonDepartment of Internal Medicine Lebanese American University Medical Center – Rizk Hospital Beirut LebanonCardiology Department Lebanese American University Medical Center – Rizk Hospital Beirut LebanonDepartment of Internal Medicine Lebanese American University Medical Center – Rizk Hospital Beirut LebanonDepartment of Internal Medicine Lebanese American University Medical Center – Rizk Hospital Beirut LebanonCardiology Department Lebanese American University Medical Center – Rizk Hospital Beirut LebanonAbstract Coronavirus disease 2019 (COVID‐19) 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‐blind, placebo‐controlled, randomized clinical trial, we assigned patients who were admitted to the hospital with mild, moderate, or severe COVID‐19 infection to receive, on top of optimal medical therapy, either an endothelial protocol consisting of (Nicorandil, L‐arginine, folate, Nebivolol, and atorvastatin) or placebo for up to 14 days. 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‐control or other nonmedical reasons. Secondary outcomes included the composite outcome of intensive care unit (ICU) admission or the need for mechanical ventilation, all‐cause 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 years; 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 [4–12] days) and the placebo group (6 [5–8] days; p value = 0.854). Furthermore, there were no statistically significant differences in the need for mechanical ventilation or ICU admission, all‐cause 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‐19 infection, targeting endothelial dysfunction by administering Nicorandil, L‐arginine, Folate, Nebivolol, and Atorvastatin on top of optimal medical therapy did not decrease time to recovery. Based on this study’s 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.https://doi.org/10.1111/cts.13369 |
| spellingShingle | Kamal Matli Abdulrahman Al Kotob Wassim Jamaleddine Soad Al Osta Pascale Salameh Rami Tabbikha Nibal Chamoun Ahmad Moussawi Jean‐Michel Saad Gibran Atwi Tarik Abu Saad Omar Jamal Jacques Mokhbat Georges Ghanem Managing endothelial dysfunction in COVID‐19 with statins, beta blockers, nicorandil, and oral supplements: A pilot, double‐blind, placebo‐controlled, randomized clinical trial Clinical and Translational Science |
| title | Managing endothelial dysfunction in COVID‐19 with statins, beta blockers, nicorandil, and oral supplements: A pilot, double‐blind, placebo‐controlled, randomized clinical trial |
| title_full | Managing endothelial dysfunction in COVID‐19 with statins, beta blockers, nicorandil, and oral supplements: A pilot, double‐blind, placebo‐controlled, randomized clinical trial |
| title_fullStr | Managing endothelial dysfunction in COVID‐19 with statins, beta blockers, nicorandil, and oral supplements: A pilot, double‐blind, placebo‐controlled, randomized clinical trial |
| title_full_unstemmed | Managing endothelial dysfunction in COVID‐19 with statins, beta blockers, nicorandil, and oral supplements: A pilot, double‐blind, placebo‐controlled, randomized clinical trial |
| title_short | Managing endothelial dysfunction in COVID‐19 with statins, beta blockers, nicorandil, and oral supplements: A pilot, double‐blind, placebo‐controlled, randomized clinical trial |
| title_sort | managing endothelial dysfunction in covid 19 with statins beta blockers nicorandil and oral supplements a pilot double blind placebo controlled randomized clinical trial |
| url | https://doi.org/10.1111/cts.13369 |
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