西地那非对间歇性跛行患者最大行走时间的影响：ARTERIOFIL 研究。
Effects of sildenafil on maximum walking time in patients with arterial claudication: The ARTERIOFIL study.
机构信息
Univ Rennes, CHU Rennes, INSERM CIC1414, Vascular Medicine Unit, F-35000 Rennes, France; MitoVasc Institute, UMR CNRS 6015 - INSERM U1083, CHU, Angers, France; Vascular Medicine Unit, Redon Hospital, 8 Rue Etienne Gascon, 35600 Redon, France.
Univ Rennes, CHU Rennes, INSERM CIC1414, Clinical Investigation Center, F-35000 Rennes, France.
出版信息
Vascul Pharmacol. 2019 Jul-Aug;118-119:106563. doi: 10.1016/j.vph.2019.05.003. Epub 2019 May 30.
BACKGROUND
Patients with lower extremity peripheral artery disease (PAD) frequently experience claudication, a clinical symptom indicative of reduced walking capacity. Recommended care consists of exercise rehabilitation combined with optimal medical treatment and surgery. The effects of a single oral dose of sildenafil, a phosphodiesterase type-5 inhibitor, on patients with claudication are discussed. The aim of this study was to test the efficacy of a single 100 mg dose of sildenafil compared to placebo in terms of maximal walking time (MWT) in patients with claudication.
METHODS
The ARTERIOFIL study is a crossover, double-blind, prospective, randomized, single-center study conducted at Angers University Hospital in France. MWT (primary endpoint) was assessed using a treadmill test (10% incline; 3.2 km/h). Secondary endpoints (pain-free walking time (PFWT), transcutaneous oximetry during exercise and redox cycle parameters and safety) were also studied.
RESULTS
Fourteen patients were included of whom two were ultimately excluded. In the 12 remaining patients, the MWT was significantly improved during the sildenafil period compared with the placebo period (300 s [95% CI 172 s-428 s] vs 402 s [95% CI 274 s-529 s] p < 0.01). Sildenafil had no significant effect on pain-free walking time or skin tissue oxygenation during exercise. According to redox cycle parameters, sildenafil significantly reduced blood glucose and pyruvate levels and the 3-hydroxybutyrate/acetoacetate ratio, while there was no significant effect on lactate, 3-hydroxybutyrate, acetoacetate and free fatty acid levels. Symptomatic transient hypotension was observed in two women.
CONCLUSIONS
The ARTERIOFIL study has shown that a single 100 mg oral dose of sildenafil had a significant effect on increase in MWT but had no significant effects on PFWT and oxygenation parameters in patients with claudication. A double-blind, prospective, randomized, multicenter study (VIRTUOSE©) is ongoing to evaluate the chronic effect of six month-long sildenafil treatment on MWT in PAD patients with claudication.
CLINICAL TRIAL REGISTRATION
This clinical trial was registered at clinicaltrials.gov, registration. number: NCT02832570, (https://clinicaltrials.gov/ct2/show/NCT02832570).
背景
下肢外周动脉疾病（PAD）患者常出现跛行，这是行走能力下降的临床症状。推荐的治疗方法包括运动康复结合最佳药物治疗和手术。本文讨论了磷酸二酯酶 5 型抑制剂西地那非单次口服剂量对跛行患者的影响。本研究的目的是测试 100mg 单剂量西地那非与安慰剂相比在跛行患者最大步行时间（MWT）方面的疗效。
方法
ARTERIOFIL 研究是一项在法国昂热大学医院进行的交叉、双盲、前瞻性、随机、单中心研究。MWT（主要终点）使用跑步机测试（10%坡度；3.2km/h）进行评估。还研究了次要终点（无痛步行时间（PFWT）、运动期间的经皮血氧饱和度和氧化还原循环参数以及安全性）。
结果
共纳入 14 名患者，其中 2 名最终被排除。在其余 12 名患者中，与安慰剂期相比，西地那非期 MWT 显著改善（300s[95%CI172s-428s]vs402s[95%CI274s-529s]，p<0.01）。西地那非对无痛步行时间或运动期间的皮肤组织氧合无显著影响。根据氧化还原循环参数，西地那非可显著降低血糖和丙酮酸水平以及 3-羟丁酸/乙酰乙酸比值，而对乳酸、3-羟丁酸、乙酰乙酸和游离脂肪酸水平无显著影响。两名女性出现短暂性症状性低血压。
结论
ARTERIOFIL 研究表明，单次口服 100mg 西地那非可显著增加 MWT，但对跛行患者的 PFWT 和氧合参数无显著影响。一项正在进行的、双盲、前瞻性、随机、多中心研究（VIRTUOSE©）旨在评估 6 个月西地那非治疗对跛行 PAD 患者 MWT 的慢性影响。
临床试验注册
该临床试验在 clinicaltrials.gov 注册，注册号：NCT02832570（https://clinicaltrials.gov/ct2/show/NCT02832570）。
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