Money S R, Herd J A, Isaacsohn J L, Davidson M, Cutler B, Heckman J, Forbes W P
Ochsner Clinic, New Orleans, La. 70121, USA.
J Vasc Surg. 1998 Feb;27(2):267-74; discussion 274-5. doi: 10.1016/s0741-5214(98)70357-x.
This study evaluated the effects of cilostazol on walking distances in patients with intermittent claudication (IC) caused by peripheral arterial occlusive disease.
The study was a multicenter, randomized, double-blind, placebo-controlled trial. Two hundred thirty-nine patients with IC were randomly assigned to receive cilostazol (100 mg b.i.d.) or a placebo for 16 weeks. All patients underwent serial, variable-grade, constant-speed treadmill testing. Absolute claudication distance (ACD), assessed at the end of the 12-hour dosing interval (trough), was the primary end point. Secondary end points included ACD assessed 3 to 4 hours after dosing (peak) and initial claudication distances (trough and peak). Functional status measures, including the Medical Outcomes Scale (SF-36) and Walking Impairment Questionnaire, were used to assess subjective changes over the 16-week treatment period. Ankle-brachial indexes were calculated from Doppler-measured systolic pressures at every visit with treadmill testing.
Patients treated with cilostazol demonstrated significant improvements over the placebo patients in ACD at all three time points tested after baseline (weeks 8, 12, and 16). Peak treadmill testing at weeks 8 and 12 also showed significant improvement in walking distances for cilostazol-treated patients over placebo-treated patients. At week 16, patients in the cilostazol group had a 96.4-meter (47%) increase in ACD compared with 31.4 meters (12.9%) for the placebo group (p < 0.001). In the SF-36, significant improvement was observed in the physical component subscale and the composite physical component score. In the Walking Impairment Questionnaire, improvements were significant in patient reports of walking speed and specific measures of walking difficulty. Ankle-brachial indexes improved in the cilostazol group (0.64 +/- 0.02 to 0.70 +/- 0.02) compared with the placebo group (0.68 +/- 0.02 to 0.69 +/- 0.02) (p < 0.0125). The most frequent adverse events were headache, abnormal stools (e.g. loose stools), diarrhea, and dizziness.
Cilostazol significantly increased ACD at all measured time points and initial claudication distances at most time points. This agent may represent a new treatment option for patients with intermittent claudication.
本研究评估西洛他唑对周围动脉闭塞性疾病所致间歇性跛行（IC）患者步行距离的影响。
该研究为多中心、随机、双盲、安慰剂对照试验。239例IC患者被随机分配接受西洛他唑（100mg，每日两次）或安慰剂治疗16周。所有患者均接受系列、可变坡度、恒速跑步机测试。在12小时给药间隔结束时（谷值）评估的绝对跛行距离（ACD）为主要终点。次要终点包括给药后3至4小时（峰值）评估的ACD以及初始跛行距离（谷值和峰值）。使用包括医学结局量表（SF - 36）和步行障碍问卷在内的功能状态测量方法来评估为期16周的治疗期间的主观变化。每次进行跑步机测试时，根据多普勒测量的收缩压计算踝臂指数。
在基线后测试的所有三个时间点（第8、12和16周），接受西洛他唑治疗的患者在ACD方面比安慰剂组患者有显著改善。在第8周和第12周的跑步机峰值测试中，接受西洛他唑治疗的患者在步行距离方面也比接受安慰剂治疗的患者有显著改善。在第16周，西洛他唑组患者的ACD增加了96.4米（47%），而安慰剂组为31.4米（12.9%）（p < 0.001）。在SF - 36中，身体成分子量表和综合身体成分得分有显著改善。在步行障碍问卷中，患者报告的步行速度和特定步行困难测量指标有显著改善。与安慰剂组（从0.68±0.02至0.69±0.02）相比，西洛他唑组的踝臂指数有所改善（从0.64±0.02至0.70±0.02）（p < 0.0125）。最常见的不良事件为头痛、大便异常（如稀便）、腹泻和头晕。
西洛他唑在所有测量时间点均显著增加ACD，且在大多数时间点增加初始跛行距离。该药物可能是间歇性跛行患者的一种新的治疗选择。
