Section of Vascular Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Mo.
Saint Louis College of Pharmacy, St. Louis, Mo.
J Vasc Surg. 2021 Feb;73(2):711-721.e3. doi: 10.1016/j.jvs.2020.08.125. Epub 2020 Sep 4.
Current clinical guidelines recommend the use of cilostazol in the treatment of patients with infrainguinal peripheral artery disease (PAD) who experience intermittent claudication. However, the role of cilostazol therapy in patients with advanced PAD and critical limb ischemia (CLI) remains unclear. To conduct a meta-analysis of randomized controlled trials and cohort studies that evaluated the effect of cilostazol vs standard antiplatelet therapy on limb-related and arterial patency-related outcomes. We also reviewed literature pertinent to the effect of cilostazol on wound healing in patients with advanced PAD.
We performed a MEDLINE, EMBASE, COCHRANE (CENTRAL), SCOPUS, and US Clinical Trials database search for all trials and studies since 1999 that compared cilostazol with standard antiplatelet therapy in the setting of infrainguinal PAD revascularization procedures (endovascular or open). Aggregate data was collected from four randomized control trials and six retrospective cohort studies. The end point incidence ratios and treatment effects were generated from each study and reported as hazard ratios (HR) using a random-effect model. We also reviewed 10 studies that evaluated the effect of cilostazol on wound healing in patients with advanced PAD.
From more than 25,000 total patients, 3136 patients met our inclusion criteria. All patients had at least lifestyle-impacting intermittent claudication, and more than 50% met the definition of CLI (Rutherford class ≥4). Patient age range was 53 to 83 years, and the majority were male (66%). The mean follow-up time averaged 2 years across all studies. Meta-analysis revealed that cilostazol treatment favored amputation-free survival (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.69-0.91), limb salvage rate (HR, 0.42; 95% CI, 0.27-0.66), decreased repeat revascularization (risk ratio [RR], 0.44; 95% CI, 0.37-0.52), and decreased restenosis (RR, 0.68; 95% CI, 0.61-0.76). Cilostazol treatment also increased freedom from target lesion revascularization (RR, 1.35; 95% CI, 1.21-1.53) with no difference in all-cause mortality. Effective wound healing was found to be an inconsistent outcome measure in patients receiving cilostazol therapy.
We observed that cilostazol therapy has a beneficial impact on all limb-related and arterial patency-related outcomes, but no effect on all-cause mortality in patients with advanced PAD and CLI undergoing revascularization procedures. Additional studies are needed to evaluate the effect of cilostazol therapy on wound healing in patients with advanced PAD.
目前的临床指南建议在出现间歇性跛行的下肢动脉疾病（PAD）患者中使用西洛他唑进行治疗。然而，西洛他唑治疗在伴有严重 PAD 和严重肢体缺血（CLI）的患者中的作用尚不清楚。本研究旨在对评估西洛他唑与标准抗血小板治疗对肢体相关和动脉通畅相关结局的影响的随机对照试验和队列研究进行荟萃分析。我们还回顾了与严重 PAD 患者的伤口愈合相关的西洛他唑作用的文献。
我们检索了自 1999 年以来比较下肢动脉血管重建术（血管内或开放）中西洛他唑与标准抗血小板治疗的所有试验和研究，检索数据库包括 MEDLINE、EMBASE、COCHRANE（CENTRAL）、SCOPUS 和美国临床试验数据库。从四项随机对照试验和六项回顾性队列研究中收集汇总数据。每个研究的终点发生率比和治疗效果均使用随机效应模型生成，并报告为风险比（HR）。我们还回顾了十项评估西洛他唑对严重 PAD 患者伤口愈合影响的研究。
在超过 25000 名患者中，有 3136 名患者符合我们的纳入标准。所有患者都至少存在影响生活方式的间歇性跛行，超过 50%的患者符合 CLI（Rutherford 分级≥4）的定义。患者年龄在 53 至 83 岁之间，大多数为男性（66%）。所有研究的平均随访时间均为 2 年。荟萃分析显示，西洛他唑治疗有利于免于截肢（HR，0.79；95%置信区间 [CI]，0.69-0.91）、肢体存活率（HR，0.42；95% CI，0.27-0.66）、减少重复血运重建（RR，0.44；95% CI，0.37-0.52）和减少再狭窄（RR，0.68；95% CI，0.61-0.76）。西洛他唑治疗还增加了免于靶病变血运重建的可能性（RR，1.35；95% CI，1.21-1.53），而全因死亡率无差异。在接受西洛他唑治疗的患者中，有效的伤口愈合被发现是一个不一致的结局测量指标。
我们观察到，在接受血管重建术的严重 PAD 和 CLI 患者中，西洛他唑治疗对所有肢体相关和动脉通畅相关结局均有有益影响，但对全因死亡率无影响。需要进一步研究来评估西洛他唑治疗对严重 PAD 患者伤口愈合的影响。
