tetano
Editor, Senior Moderator
Clin Transl Sci
. 2022 Jul 8.
doi: 10.1111/cts.13369. Online ahead of print.
Managing Endothelial Dysfunction in COVID-19 with Statins, Beta Blockers, Nicorandil and Oral Supplements: A Pilot, Double-Blind, Placebo-Controlled, Randomized Clinical Trial
Kamal Matli[SUP] 1 2 [/SUP], Abdulrahman Al Kotob[SUP] 3 [/SUP], Wassim Jamaleddine[SUP] 3 [/SUP], Soad Al Osta[SUP] 3 4 [/SUP], Pascale Salameh[SUP] 4 5 6 7 [/SUP], Rami Tabbikha[SUP] 3 [/SUP], Nibal Chamoun[SUP] 8 [/SUP], Ahmad Moussawi[SUP] 3 [/SUP], Jean-Michel Saad[SUP] 3 [/SUP], Gibran Atwi[SUP] 3 4 [/SUP], Tarik Abu Saad[SUP] 1 [/SUP], Omar Jamal[SUP] 3 [/SUP], Jacques Mokhbat[SUP] 3 [/SUP], Georges Ghanem[SUP] 1 [/SUP]
Affiliations
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 8 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 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 BMI 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, and 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 findings, targeting endothelial dysfucntion did not result in a clinically significant improvement in outcome and as such larger trials targeting this pathway are not recommended.
. 2022 Jul 8.
doi: 10.1111/cts.13369. Online ahead of print.
Managing Endothelial Dysfunction in COVID-19 with Statins, Beta Blockers, Nicorandil and Oral Supplements: A Pilot, Double-Blind, Placebo-Controlled, Randomized Clinical Trial
Kamal Matli[SUP] 1 2 [/SUP], Abdulrahman Al Kotob[SUP] 3 [/SUP], Wassim Jamaleddine[SUP] 3 [/SUP], Soad Al Osta[SUP] 3 4 [/SUP], Pascale Salameh[SUP] 4 5 6 7 [/SUP], Rami Tabbikha[SUP] 3 [/SUP], Nibal Chamoun[SUP] 8 [/SUP], Ahmad Moussawi[SUP] 3 [/SUP], Jean-Michel Saad[SUP] 3 [/SUP], Gibran Atwi[SUP] 3 4 [/SUP], Tarik Abu Saad[SUP] 1 [/SUP], Omar Jamal[SUP] 3 [/SUP], Jacques Mokhbat[SUP] 3 [/SUP], Georges Ghanem[SUP] 1 [/SUP]
Affiliations
- PMID: 35808843
- DOI: 10.1111/cts.13369
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 8 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 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 BMI 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, and 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 findings, targeting endothelial dysfucntion did not result in a clinically significant improvement in outcome and as such larger trials targeting this pathway are not recommended.