Robertson Lindsay, Andras Alina
Centre for Population Health Sciences, The Medical School, The University of Edinburgh, Teviot Place, Edinburgh, UK, EH8 9AG.
Cochrane Database Syst Rev. 2013 Apr 30;2013(4):CD000986. doi: 10.1002/14651858.CD000986.pub3.
Peripheral arterial disease (PAD) is a common cause of morbidity in the general population. While numerous studies have established the efficacy of prostanoids in PAD stages III and IV, the question of the role of prostanoids as an alternative or additive treatment in patients suffering from intermittent claudication (PAD II) has not yet been clearly answered. This is an update of a Cochrane Review first published in 2004.
To determine the effects of prostanoids in patients with intermittent claudication (IC) Fontaine stage II.
For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Clinical trials databases were searched for details of ongoing or unpublished studies. In addition, reference lists of relevant articles were checked.
Randomised clinical trials of prostanoids versus placebo or alternative ('control') treatment in people with intermittent claudication were considered for inclusion.
Two authors independently assessed trial quality and extracted data. Primary outcomes included pain-free walking distance (PFWD) and maximum walking distance (MWD), presented as mean change in walking distance during the course of the trial (% improvement) and as final walking distance (that is walking distance, in metres, after treatment) for the prostanoid and control groups.
Eighteen trials with a total of 2773 patients were included (16 in the original review and a further two in this update). As the majority of trials did not report standard deviations for the primary PFWD and MWD outcomes, it was often not possible to test for the statistical significance of any improvements in walking distance between groups. The quality of individual trials was variable and usually unclear due to insufficient reporting information. Comparison between trials was hampered by the use of different treadmill testing protocols, including different walking speeds and gradients. Such limitations in the data and the trial heterogeneity meant it was not possible to meaningfully pool results by meta-analysis.Four trials compared prostaglandin E1 (PGE1) with placebo; individual trials showed significant increases in walking distances with administration of PGE1 and in several trials the walking capacity remained increased after termination of treatment. Compared with pentoxifylline, PGE1 was associated with a higher final PFWD and MWD but these results were based on final walking distances rather than changes in walking distance from baseline. When PGE1 was compared with other treatments including laevadosin, naftidrofuryl and L-arginine, improvements in walking distances over time were observed for both PGE1 and the alternative treatment, but it was not possible from the data available to analyse statistically whether or not one treatment was more effective than the other.Six studies compared various preparations of prostacyclins (PGI2) with placebo. In one study using three different dosages of iloprost, PFWD and MWD appeared to increase in a dose-dependent manner; iloprost was associated with headache, pain, nausea and diarrhoea, leading to a higher rate of treatment withdrawal. Of three studies using beraprost sodium, one showed an improvement in PFWD and MWD compared with placebo while two showed no significant benefit. Beraprost sodium was associated with an increased incidence of drug-related adverse events. Of two studies on taprostene, the results of one in particular must be interpreted with caution due to an imbalance in walking capacity at baseline.Comprehensive, high quality data on outcomes such as quality of life, ankle brachial index, venous occlusion plethysmography and haemorrheological parameters were lacking.
AUTHORS' CONCLUSIONS: Whilst results from some individual studies suggested a beneficial effect of PGE1, the quality of these studies and of the overall evidence available is insufficient to determine whether or not patients with intermittent claudication derive clinically meaningful benefit from the administration of prostanoids. Further well-conducted randomised, double blinded trials with a sufficient number of participants to provide statistical power are required to answer this question.
外周动脉疾病（PAD）是普通人群发病的常见原因。虽然众多研究已证实前列腺素类药物在PAD III期和IV期的疗效，但前列腺素类药物作为间歇性跛行（PAD II）患者的替代或辅助治疗的作用问题尚未得到明确解答。这是对2004年首次发表的Cochrane系统评价的更新。
确定前列腺素类药物对Fontaine II期间歇性跛行（IC）患者的影响。
本次更新中，Cochrane外周血管疾病组试验检索协调员（TSC）检索了专业注册库（最后检索时间为2013年1月）和CENTRAL（2012年第12期）。检索临床试验数据库以获取正在进行或未发表研究的详细信息。此外，还检查了相关文章的参考文献列表。
纳入前列腺素类药物与安慰剂或替代（“对照”）治疗对比的间歇性跛行患者的随机临床试验。
两位作者独立评估试验质量并提取数据。主要结局包括无痛行走距离（PFWD）和最大行走距离（MWD），以试验过程中行走距离的平均变化（改善百分比）以及前列腺素类药物组和对照组的最终行走距离（即治疗后的行走距离，单位为米）表示。
共纳入18项试验，涉及2773例患者（原始评价纳入16项试验，本次更新新增2项试验）。由于大多数试验未报告主要PFWD和MWD结局的标准差，因此通常无法检验组间行走距离改善的统计学显著性。由于报告信息不足，各试验的质量参差不齐且通常不明确。不同跑步机测试方案（包括不同的行走速度和坡度）的使用阻碍了试验间的比较。数据和试验异质性方面的这些限制意味着无法通过Meta分析有意义地汇总结果。4项试验比较了前列腺素E1（PGE1）与安慰剂；个别试验显示给予PGE1后行走距离显著增加，且在几项试验中，治疗终止后行走能力仍保持增加。与己酮可可碱相比，PGE1与更高的最终PFWD和MWD相关，但这些结果基于最终行走距离而非相对于基线的行走距离变化。当将PGE1与其他治疗（包括左多巴汀、萘呋胺酯和L - 精氨酸）进行比较时，PGE1和替代治疗随时间均观察到行走距离的改善，但根据现有数据无法从统计学上分析一种治疗是否比另一种更有效。6项研究比较了各种前列环素（PGI2）制剂与安慰剂。在一项使用三种不同剂量伊洛前列素的研究中，PFWD和MWD似乎呈剂量依赖性增加；伊洛前列素与头痛、疼痛、恶心和腹泻相关，导致更高的治疗退出率。在三项使用贝前列素钠的研究中，一项显示与安慰剂相比PFWD和MWD有所改善，而两项显示无显著益处。贝前列素钠与药物相关不良事件的发生率增加相关。在两项关于他前列烯的研究中，其中一项研究的结果因基线时行走能力不平衡而必须谨慎解读。缺乏关于生活质量、踝肱指数、静脉闭塞体积描记法和血液流变学参数等结局的全面、高质量数据。
虽然一些个别研究的结果表明PGE1有有益作用，但这些研究以及现有总体证据的质量不足以确定间歇性跛行患者使用前列腺素类药物是否能获得临床有意义的益处。需要进一步进行设计良好的随机、双盲试验，纳入足够数量的参与者以提供统计学效力来回答这个问题。
