地奥司明治疗下肢慢性静脉疾病的多中心前瞻性临床研究

Multicenter prospective clinical study of diosmin in treatment of lower-limb chronic venous diseases

目的:观察地奥司明治疗不同CEAP分级的下肢慢性静脉疾病(CVD)的有效性以及安全性。方法:选择240例CEAP分级C0～C3未行手术的下肢CVD反流性病变患者与240例CEAP分级C4～C6行大隐静脉剥离术后的下肢CVD反流性病变患者,分别随机分为试验组(口服地奥司明+弹力袜加压)与对照组(单纯弹力袜加压),检测患者试验前后下肢腿围与其他主观症状,并检测血常规、肝功能、肾功能、血糖等安全性指标,记录不良事件。结果:480例患者中,完成24周统计者438例,脱落42例(8.75%)。未行手术的C0～C3 CVD患者中,试验组与对照组治疗4、12、24周患肢的脚踝周径均较治疗前明显减小,但试验组在治疗12、24周患肢的脚踝周径减小程度明显大于对照组(均P<0.05);两组患者治疗后主观症状均明显改善,但试验组治疗24周的沉重感以及腿部肿胀感缓解方面优于保守治疗对照组(均P<0.05)。经手术治疗的C4～C6 CVD患者中,试验组治疗4、12、24周,对照组治疗12、24周患肢的脚踝周径均较治疗前明显减小,且试验组小腿周径减小程度在12、24周均明显大于对照组(均P<0.05);两组患者治疗后主观症状均明显改善,但试验组治疗24周的沉重感以及腿部肿胀感缓解方面优于保守治疗对照组(均P<0.05)。试验过程中,7例(1.60%)发生胃肠道反应,均能耐受并未致停止用药;所有患者生化指标均正常。结论:地奥司明能够有效减轻各级下肢CVD患者的水肿和缓解相关症状,且安全性良好,建议作为下肢CVD全程治疗的基础用药,且至少服用3～6个月。

Objective: To observe the efficacy and safety of diosmin administration for patients with lower-limb chronic venous diseases (CVD) of different CEAP grades.Methods: Two hundred and forty patients with CEAP class C0-C3 CVD and reflux of the lower limb without prior surgical treatment, and 240 patients with CEAP class C4-C6 CVD and reflux of the lower limb after long saphenous vein (LSV) stripping were enrolled, and were randomly assigned to respective study group (oral administration plus compression stocking therapy) and control group (compression stocking therapy alone). The calf circumference and subjective symptoms of the patients were examined before and after treatment, and the safety variables such as blood routine, liver function, renal function and blood glucose were determined, and the adverse events were also recorded.Results:In the 480 patients, 24-week study was completed in 438 cases and 42 cases (8.75%) dropped out from the study. In patients with C0-C3 CVD without prior surgical treatment, the ankle circumferences of the affected leg at 4,12 and 24 weeks after treatment were all significantly decreased in both study group and control group compared with their values before treatment, but the decreasing amplitudes were significantly greater in study group than those in control group at 12 and 24 weeks after treatment (all P<0.05); the subjective symptoms were all improved in both groups, but study group was superior to control group in terms of improving sensation of heaviness and swelling of the leg at 24 weeks after treatment (both P<0.05). In patients with C4-C6 CVD having prior surgical treatment, the ankle circumferences of the affected leg in study group at 4, 12 and 24 weeks after treatment and in control group at 12 and 24 weeks after treatment were all significantly decreased compared with their values before treatment, but the decreasing amplitudes were significantly greater in study group than those in control group at 12 and 24 weeks after treatment (all P<0.05); the subjective symptoms were all improved in both groups, but study group was superior to control group in terms of improving sensation of heaviness and swelling of the leg at 24 weeks after treatment (both P<0.05). During the study, gastrointestinal reactions occurred in 7 patients (1.60%), and those were all tolerable without causing discontinuation of medication; the observed biochemical parameters were all normal in all of the patients.Conclusion: Diosmin can effectively alleviate the edema and symptoms of lower-limb CVD patients of different severities, and with good safety. Therefore, it is recommended to be used as a basic medication for lower-limb CVD during the entire treatment course, with an administration time of at least 3 to 6 months.