Catheter‐directed thrombolysis for deep venous thrombosis might be cost‐effective, but for whom?
Catheter‐directed thrombolysis for deep venous thrombosis might be cost‐effective, but for whom?
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DOI：
10.1111/jth.12246
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发表时间：
2013-06
影响因子：
10.4
通讯作者：
Arnaud Perrier;Henri Bounameaux
中科院分区：
文献类型：
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作者：
Arnaud Perrier;Henri Bounameaux
血栓后综合征(PTS)仍然是深静脉血栓形成(DVT)患者的一个重要问题。由于定义和时间范围的不同，其频率在各系列中从20%到50%不等；因此，很难比较预防干预措施的有效性。最近一项使用Villalta评分系统的前瞻性研究证实，急性DVT后2年，30%的患者为轻度PTS，10%为中度PTS，3%为重度PTS[1]。预测更严重的PTS的因素是股静脉或髂静脉血栓、既往DVT、高体重指数、年龄和女性。在DVT后的最初3-6个月内，充分的抗凝似乎是有保护作用的。在最近的一项反向研究队列分析中，34%的抗凝效果不佳的患者(INR低于2.0的时间超过20%)发生PTS，而接受较好治疗的患者中只有22%[2]。压缩长袜也是有效的，正如几个小型随机试验所证明的那样。Cochrane Collaboration Meta分析表明，压缩长袜可使PTS减少69%(优势比，0.31；95%CI，0.20-0.48)，严重PTS的PTS减少类似的61%[3]。然而，即使使用膝盖以下的袜子，对这种简单干预的坚持也很差，最近仍未发表的多中心随机SOX试验对其有效性提出了质疑[4]。因此，预防PTS的进展当然是有必要的，尤其是对于风险较高的髂股深静脉血栓患者；因此，最近人们对旨在通过机械手段恢复静脉通畅的更具侵入性的方法感兴趣，如支架植入或导管定向溶栓。挪威的导管定向静脉溶栓(CaVenT)研究是唯一发表的随机试验，通过充分的24个月的随访评估了这项技术，并得出了积极的结果。然而，该技术具有侵入性，资源密集型，成本高昂，并增加了出血风险。对其成本效益的评估无疑是有必要的。CaVenT研究的研究人员已经进行了这样的分析，并发表在本期的血栓和止血杂志上。成本效益分析是现实的模型，有它们自己的一套潜在偏差[7]，主要关注的是模型所基于的数据的稳健性和准确性。这需要更仔细地研究CaVenT研究的结果，因为它提供了模型中包含的几个主要数字。这项研究是一项随机开放试验，包括209名首发急性髂股深静脉血栓的患者，他们要么接受阿尔替普酶(CDT)导管定向溶栓治疗，要么接受常规治疗。两组都接受了抗凝治疗和膝下压缩袜子。两组在预后因素方面存在差异，如更好的抗凝治疗和CDT组更高的对压缩袜子的依从性(63%对51%在24个月时仍在使用它们)，这可能是由开放标签设计解释的。主要终点，即在24个月时用维拉尔塔评分评估PTS的频率，可以在189名患者中进行评估。令人惊讶的是，虽然干预组和对照组在6个月时发生PTS的频率没有差异(30%比32%)，尽管髂股动脉通畅率有显著差异(66%比47%)，但在24个月时介入治疗组PTS的发生率显著低于对照组(41%比56%，P=0.047)。对照组在24个月时仅有一例严重PTS。溶栓组的出血风险更高(三次大出血与对照组无大出血相比)[5]。为了评估CDT的成本效益，作者设计了一个遵循适当方法的马尔可夫模型：日内瓦大学医院普通内科Arnaud Perrier，Rue Gabrielle-Perret-Gentil 4，CH-1211日内瓦14，瑞士。电话：+41 22 372 90 50传真：+41 22 372 91 16电子邮件：arnaud.perrier@hcuge.ch
Post-thrombotic syndrome (PTS) remains an important concern in patients who suffer from a deep venous thrombosis (DVT). Its frequency varies from 20 to 50% across series, due to differences in definition and time-frame; therefore comparing the effectiveness of preventive interventions is difficult. A fairly recent prospective study using the Villalta scoring system established that 30% of patients had mild, 10% had moderate and 3% had severe PTS 2 years after an acute DVT [1]. Predictors of more severe PTS were femoral or iliac vein thrombosis, previous DVT, high body mass index, older age and female gender. Adequate anticoagulation during the initial 3–6 months following DVT appears to be protective. In a recent analysis of the REVERSE study cohort, 34% of patients with suboptimal anticoagulation (INR below 2.0 more than 20% of the time) developed PTS compared with only 22% of those who were better treated [2]. Compression stockings are also effective, as demonstrated by several small randomized trials. A Cochrane Collaboration meta-analysis suggests a 69% reduction of PTS by compression stockings (odds ratio, 0.31; 95% CI, 0.20– 0.48) and a similar 61% reduction in severe PTS [3]. However, adherence to that simple intervention is poor even using below-knee stockings and the still unpublished multicenter randomized SOX trial recently casted doubt on its efficacy [4]. Therefore, progress is certainly warranted to prevent PTS, especially in patients with iliofemoral DVT who are at higher risk; hence the recent interest in more invasive approaches aimed at restoring venous patency by mechanical means, such as stenting or catheter-directed thrombolysis. The Catheter-directed Venous Thrombolysis (CaVenT) study [5] from Norway is the only published randomized trial that assessed this technique with an adequate 24-month follow-up and it yielded positive results. However, the technique is invasive, resource-intensive, costly and increases the bleeding risk. An evaluation of its costeffectiveness was definitely warranted. Such an analysis has been carried out by the investigators of the CaVenT study and is published in this issue of the Journal of Thrombosis and Haemostasis [6]. Cost-effectiveness analyses are models of reality and have their own set of potential biases [7], the main concern being the robustness and accuracy of the data on which the model is based. This warrants a closer look at the results of the CaVenT study because it provided several major figures included in the model. The study was a randomized open-label trial including 209 patients with a first episode of acute iliofemoral DVT treated either by catheter-directed thrombolysis with alteplase (CDT) or conventional treatment. Both groups received anticoagulant treatment and below-knee compression stockings. The two groups differed regarding prognostic factors such as better anticoagulant treatment and higher adherence to compression stockings in the CDT arm (63% vs. 51% still using them at 24 months), which might be explained by the open-label design. The main endpoint, the frequency of PTS as assessed by the Villalta score at 24 months, could be assessed in 189 patients. Surprisingly, while there was no difference at 6 months between the intervention and control groups in terms of frequency of PTS (30% vs. 32%) despite a significant difference in iliofemoral patency (66% vs. 47%), PTS was significantly less frequent in the CDT group at 24 months (41% vs. 56%, P = 0.047). There was only one case of severe PTS at 24 months in the control group. Bleeding risk was higher in the thrombolysis group (three major bleeds vs. none in the control group) [5]. To assess the cost-effectiveness of CDT, the authors designed a Markov model that adhered to adequate methCorrespondence: Arnaud Perrier, Division of General Internal Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva 14, Switzerland. Tel.: +41 22 372 90 50; fax: +41 22 372 91 16. E-mail: arnaud.perrier@hcuge.ch