Fakhry Farzin, Fokkenrood Hugo Jp, Spronk Sandra, Teijink Joep Aw, Rouwet Ellen V, Hunink M G Myriam
Departments of Epidemiology & Radiology, Erasmus MC, Dr Molewaterplein 40, PO Box 2040, Rotterdam, Netherlands, 3015 GD.
Cochrane Database Syst Rev. 2018 Mar 8;3(3):CD010512. doi: 10.1002/14651858.CD010512.pub2.
Intermittent claudication (IC) is the classic symptomatic form of peripheral arterial disease affecting an estimated 4.5% of the general population aged 40 years and older. Patients with IC experience limitations in their ambulatory function resulting in functional disability and impaired quality of life (QoL). Endovascular revascularisation has been proposed as an effective treatment for patients with IC and is increasingly performed.
The main objective of this systematic review is to summarise the (added) effects of endovascular revascularisation on functional performance and QoL in the management of IC.
For this review the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (February 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). The CIS also searched trials registries for details of ongoing and unpublished studies.
Randomised controlled trials (RCTs) comparing endovascular revascularisation (± conservative therapy consisting of supervised exercise or pharmacotherapy) versus no therapy (except advice to exercise) or versus conservative therapy (i.e. supervised exercise or pharmacotherapy) for IC.
Two review authors independently selected studies, extracted data, and assessed the methodological quality of studies. Given large variation in the intensity of treadmill protocols to assess walking distances and use of different instruments to assess QoL, we used standardised mean difference (SMD) as treatment effect for continuous outcome measures to allow standardisation of results and calculated the pooled SMD as treatment effect size in meta-analyses. We interpreted pooled SMDs using rules of thumb (< 0.40 = small, 0.40 to 0.70 = moderate, > 0.70 = large effect) according to the Cochrane Handbook for Systematic Reviews of Interventions. We calculated the pooled treatment effect size for dichotomous outcome measures as odds ratio (OR).
We identified ten RCTs (1087 participants) assessing the value of endovascular revascularisation in the management of IC. These RCTs compared endovascular revascularisation versus no specific treatment for IC or conservative therapy or a combination therapy of endovascular revascularisation plus conservative therapy versus conservative therapy alone. In the included studies, conservative treatment consisted of supervised exercise or pharmacotherapy with cilostazol 100 mg twice daily. The quality of the evidence ranged from low to high and was downgraded mainly owing to substantial heterogeneity and small sample size.Comparing endovascular revascularisation versus no specific treatment for IC (except advice to exercise) showed a moderate effect on maximum walking distance (MWD) (SMD 0.70, 95% confidence interval (CI) 0.31 to 1.08; 3 studies; 125 participants; moderate-quality evidence) and a large effect on pain-free walking distance (PFWD) (SMD 1.29, 95% CI 0.90 to 1.68; 3 studies; 125 participants; moderate-quality evidence) in favour of endovascular revascularisation. Long-term follow-up in two studies (103 participants) showed no clear differences between groups for MWD (SMD 0.67, 95% CI -0.30 to 1.63; low-quality evidence) and PFWD (SMD 0.69, 95% CI -0.45 to 1.82; low-quality evidence). The number of secondary invasive interventions (OR 0.81, 95% CI 0.12 to 5.28; 2 studies; 118 participants; moderate-quality evidence) was also not different between groups. One study reported no differences in disease-specific QoL after two years.Data from five studies (n = 345) comparing endovascular revascularisation versus supervised exercise showed no clear differences between groups for MWD (SMD -0.42, 95% CI -0.87 to 0.04; moderate-quality evidence) and PFWD (SMD -0.05, 95% CI -0.38 to 0.29; moderate-quality evidence). Similarliy, long-term follow-up in three studies (184 participants) revealed no differences between groups for MWD (SMD -0.02, 95% CI -0.36 to 0.32; moderate-quality evidence) and PFWD (SMD 0.11, 95% CI -0.26 to 0.48; moderate-quality evidence). In addition, high-quality evidence showed no difference between groups in the number of secondary invasive interventions (OR 1.40, 95% CI 0.70 to 2.80; 4 studies; 395 participants) and in disease-specific QoL (SMD 0.18, 95% CI -0.04 to 0.41; 3 studies; 301 participants).Comparing endovascular revascularisation plus supervised exercise versus supervised exercise alone showed no clear differences between groups for MWD (SMD 0.26, 95% CI -0.13 to 0.64; 3 studies; 432 participants; moderate-quality evidence) and PFWD (SMD 0.33, 95% CI -0.26 to 0.93; 2 studies; 305 participants; moderate-quality evidence). Long-term follow-up in one study (106 participants) revealed a large effect on MWD (SMD 1.18, 95% CI 0.65 to 1.70; low-quality evidence) in favour of the combination therapy. Reports indicate that disease-specific QoL was comparable between groups (SMD 0.25, 95% CI -0.05 to 0.56; 2 studies; 330 participants; moderate-quality evidence) and that the number of secondary invasive interventions (OR 0.27, 95% CI 0.13 to 0.55; 3 studies; 457 participants; high-quality evidence) was lower following combination therapy.Two studies comparing endovascular revascularisation plus pharmacotherapy (cilostazol) versus pharmacotherapy alone provided data showing a small effect on MWD (SMD 0.38, 95% CI 0.08 to 0.68; 186 participants; high-quality evidence), a moderate effect on PFWD (SMD 0.63, 95% CI 0.33 to 0.94; 186 participants; high-quality evidence), and a moderate effect on disease-specific QoL (SMD 0.59, 95% CI 0.27 to 0.91; 170 participants; high-quality evidence) in favour of combination therapy. Long-term follow-up in one study (47 participants) revealed a moderate effect on MWD (SMD 0.72, 95% CI 0.09 to 1.36; P = 0.02) in favour of combination therapy and no clear differences in PFWD between groups (SMD 0.54, 95% CI -0.08 to 1.17; P = 0.09). The number of secondary invasive interventions was comparable between groups (OR 1.83, 95% CI 0.49 to 6.83; 199 participants; high-quality evidence).
AUTHORS' CONCLUSIONS: In the management of patients with IC, endovascular revascularisation does not provide significant benefits compared with supervised exercise alone in terms of improvement in functional performance or QoL. Although the number of studies is small and clinical heterogeneity underlines the need for more homogenous and larger studies, evidence suggests that a synergetic effect may occur when endovascular revascularisation is combined with a conservative therapy of supervised exercise or pharmacotherapy with cilostazol: the combination therapy seems to result in greater improvements in functional performance and in QoL scores than are seen with conservative therapy alone.
间歇性跛行（IC）是外周动脉疾病的典型症状形式，估计影响40岁及以上普通人群的4.5%。IC患者的行走功能受限，导致功能残疾和生活质量（QoL）受损。血管内血运重建已被提议作为IC患者的有效治疗方法，并且越来越多地被采用。
本系统评价的主要目的是总结血管内血运重建在IC管理中对功能表现和QoL的（附加）影响。
对于本评价，Cochrane血管信息专家（CIS）检索了专业注册库（2017年2月）和Cochrane对照试验中央注册库（CENTRAL；2017年第1期）。CIS还检索了试验注册库以获取正在进行和未发表研究的详细信息。
随机对照试验（RCT），比较血管内血运重建（±由监督运动或药物治疗组成的保守治疗）与无治疗（除运动建议外）或与保守治疗（即监督运动或药物治疗）用于IC。
两位评价作者独立选择研究、提取数据并评估研究的方法学质量。鉴于评估步行距离的跑步机方案强度差异很大以及使用不同工具评估QoL，我们使用标准化均数差（SMD）作为连续结局测量的治疗效果，以实现结果标准化，并在荟萃分析中计算合并SMD作为治疗效果大小。我们根据《Cochrane干预措施系统评价手册》使用经验法则（<0.40 = 小，0.40至0.70 = 中等，>0.70 = 大效应）解释合并SMD。我们计算二分结局测量的合并治疗效果大小为比值比（OR）。
我们确定了10项RCT（1087名参与者），评估血管内血运重建在IC管理中的价值。这些RCT比较了血管内血运重建与IC的无特定治疗或保守治疗，或血管内血运重建加保守治疗与单独保守治疗的联合治疗。在纳入的研究中，保守治疗包括监督运动或每天两次服用100 mg西洛他唑的药物治疗。证据质量从低到高不等，主要由于显著的异质性和小样本量而被降级。比较血管内血运重建与IC的无特定治疗（除运动建议外）显示对最大步行距离（MWD）有中等效应（SMD 0.70，95%置信区间（CI）0.31至1.08；3项研究；125名参与者；中等质量证据），对无痛步行距离（PFWD）有大效应（SMD 1.29，95% CI 0.90至1.68；3项研究；125名参与者；中等质量证据），支持血管内血运重建。两项研究（103名参与者）的长期随访显示，两组在MWD（SMD 0.67，95% CI -0.30至1.63；低质量证据）和PFWD（SMD 0.69，95% CI -0.45至1.82；低质量证据）方面没有明显差异。两组间二次侵入性干预的数量（OR 0.81，95% CI 0.12至5.28；2项研究；118名参与者；中等质量证据）也没有差异。一项研究报告两年后疾病特异性QoL没有差异。来自五项研究（n = 345）比较血管内血运重建与监督运动的数据显示，两组在MWD（SMD -0.42，95% CI -0.87至0.04；中等质量证据）和PFWD（SMD -0.05，95% CI -0.38至0.29；中等质量证据）方面没有明显差异。同样，三项研究（184名参与者）的长期随访显示，两组在MWD（SMD -0.02，95% CI -0.36至0.32；中等质量证据）和PFWD（SMD 0.11，95% CI -0.26至0.48；中等质量证据）方面没有差异。此外，高质量证据显示，两组在二次侵入性干预的数量（OR 1.40，95% CI 0.70至2.80；4项研究；395名参与者）和疾病特异性QoL（SMD 0.18，95% CI -0.04至0.41；3项研究；301名参与者）方面没有差异。比较血管内血运重建加监督运动与单独监督运动显示，两组在MWD（SMD 0.26，95% CI -0.13至0.64；3项研究；432名参与者；中等质量证据）和PFWD（SMD 0.33，95% CI -0.26至0.93；2项研究；305名参与者；中等质量证据）方面没有明显差异。一项研究（106名参与者）的长期随访显示，联合治疗对MWD有大效应（SMD 1.18，95% CI 0.65至1.70；低质量证据）。报告表明，两组间疾病特异性QoL相当（SMD 0.25, 95% CI -0.05至0.56；2项研究；330名参与者；中等质量证据），联合治疗后二次侵入性干预的数量（OR 0.27，95% CI 0.13至0.55；3项研究；457名参与者；高质量证据）更低。两项比较血管内血运重建加药物治疗（西洛他唑）与单独药物治疗的研究提供的数据显示，联合治疗对MWD有小效应（SMD 0.38，95% CI 0.08至0.
