Shahbazi Shaahin, Shahbazi Erfan, Zayeri Farid, Vahdat Shariatpanahi Zahra
Department of Internal Medicine, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
J Cachexia Sarcopenia Muscle. 2025 Apr;16(2):e13753. doi: 10.1002/jcsm.13753.
Endothelial damage induces myofibrillar breakdown and muscle degradation in COVID-19 infection. There is a relationship between increased endothelin-1 synthesis and sarcopenia. We evaluated the preventive effect of early bosentan therapy as an endothelin receptor blocker in sarcopenia in high-risk outpatients with COVID-19 infection.
From 15 December 2021 to 15 August 2023, patients within 3 days of the onset of signs and symptoms were randomly assigned to receive bosentan, 62.5 mg, or placebo, twice daily from enrollment for 30 days. The primary outcome was disease progression (death or hospitalization within 15 days after randomization), and the data for this outcome have been previously published. Sarcopenia as a secondary outcome was assessed prospectively at 3, 6, 9 and 12 months after randomization using the criteria of the Asian Working Group for Sarcopenia (AWGS) 2019 (IRCT.ir, IRCT20211203053263N1).
A total of 313 patients (156 bosentan group, 157 controls) were included in the analyses, which were performed under the intent-to-treat principle. Overall, the incidence of sarcopenia was 8.6% (n = 27). Nineteen (73%) had severe sarcopenia. At the 3-month follow-up, the incidence of sarcopenia was 8.3% in the total population, with the significant risk difference (RD) of -10.17% in the bosentan group versus the control group. The incidence in the total population and RD in the bosentan group versus the control group at months 6, 9 and 12 were 8.6% (RD: -10.81%, p < 0.001), 8.3% (RD: -10.17%, p = 0.001) and 5.4% (RD: -6.99%, p = 0.003), respectively. During the study, 29 people developed severe COVID-19 and were hospitalized. At follow-up, sarcopenia occurred in four inpatients and 23 outpatients (p = 0.23). Mortality occurred in 5.1% (n = 16) of the total population, including 4 (1.3%) of the patients in the bosentan group and 12 (3.8%) of the patients in the placebo group (p = 0.069). None of the patients who died had sarcopenia. Bosentan did not cause any severe adverse events and was well tolerated.
Early administration of bosentan may prevent sarcopenia in high-risk outpatients with COVID-19.
内皮损伤可导致新型冠状病毒肺炎（COVID-19）感染患者出现肌原纤维断裂和肌肉退化。内皮素-1合成增加与肌肉减少症之间存在关联。我们评估了早期使用波生坦作为内皮素受体阻滞剂对COVID-19感染高危门诊患者肌肉减少症的预防作用。
从2021年12月15日至2023年8月15日，将出现症状和体征3天内的患者随机分组，从入组开始，每日两次服用62.5mg波生坦或安慰剂，持续30天。主要结局为疾病进展（随机分组后15天内死亡或住院），该结局的数据此前已发表。作为次要结局的肌肉减少症在随机分组后3、6、9和12个月时，使用亚洲肌肉减少症工作组（AWGS）2019年标准进行前瞻性评估（IRCT.ir，IRCT20211203053263N1）。
分析共纳入313例患者（波生坦组156例，对照组157例），分析按照意向性治疗原则进行。总体而言，肌肉减少症的发生率为8.6%（n = 27）。19例（73%）为重度肌肉减少症。在3个月随访时，总体人群中肌肉减少症的发生率为8.3%，波生坦组与对照组的显著风险差异（RD）为-10.17%。在6、9和12个月时，总体人群中的发生率以及波生坦组与对照组的RD分别为8.6%（RD：-10.81%，p < 0.001）、8.3%（RD：-10.17%，p = 0.001）和5.4%（RD：-6.99%，p = 0.003）。在研究期间，29人发展为重症COVID-19并住院。随访时，4例住院患者和23例门诊患者发生了肌肉减少症（p = 0.23）。总人群的死亡率为5.1%（n = 16），其中波生坦组4例（1.3%），安慰剂组12例（3.8%）（p = 0.069）。死亡患者均无肌肉减少症。波生坦未引起任何严重不良事件，耐受性良好。
早期给予波生坦可能预防COVID-19感染高危门诊患者的肌肉减少症。
