必赢亚娱乐官网(中国)有限公司

【点评】美国FDA发布关于药物洗脱外周球囊和支架警示信

2019-02-19 11:44 ?阅读数:2949 标签:

下载 (1).jpg


2019年1月17日美国FDA在其官网上发布了“紫杉醇涂层球囊和紫杉醇洗脱支架治疗外周动脉疾病可能增加死亡率”的风险警示信。


FDA通过最近发表在《美国心脏协会杂志》(JAHA)上的一项随机试验Meta分析的研究结果,提示相关外周血管介入医师,与使用对照设备(非涂层球囊或裸金属支架)治疗的患者相比,使用紫杉醇药物洗脱球囊和紫杉醇药物洗脱支架治疗的PAD患者两年后的死亡率可能会增加。


该项目研究的题目为《Risk of Death Following Application of Paclitaxel Coated Balloons and Stents in the Femoropopliteal Artery of the Leg: A Systematic Review and Meta-Analysis of Randomized Controlled Trials》,该文章对治疗股动脉和/或腘动脉狭窄的紫杉醇药物洗脱球囊或洗脱支架的RCT研究进行了Meta分析。主要的安全性评价指标是全因死亡率。采用随机效应模型进行数据汇总。该研究共分析28个RCT研究涉及4663例受试者(89%的受试者存在间歇性跛行)。紫杉醇组和对照组1年的全因死亡率相似[(2.3% vs 2.3%;RR=1.08,RR 95% CI(0.72~1.61)]。紫杉醇组2年全因死亡率明显高于对照组[7.2% vs 3.8%;RR=1.68,RR 95% CI(1.15~2.47)]。紫杉醇组的全因死亡5年进一步增加[14.7% vs 8.1%;RR=1.93,RR 95% CI(1.27~2.93)]。Meta回归分析显示紫杉醇组暴露剂量与绝对死亡风险之间存在显著关系。


基于该项研究结论,FDA建议相关外周血管介入医师按照现行护理标准,继续监测使用紫杉醇药物洗脱球囊和紫杉醇洗脱支架治疗的患者。在临床决策中,需要与患者讨论PAD的所有可用治疗方案的风险和好处。报告使用紫杉醇药物洗脱球囊和紫杉醇洗脱支架所发生的任何不良事件或疑似不良事件。


而FDA目前正在评估现有的长期随访数据,以确定是否存在与紫杉醇药物洗脱产品相关的长期风险。这将包括对已气批准的美国紫杉醇药物洗脱球囊或紫杉醇洗脱支架的研究和其他可用数据集的长期随访数据的评估。


但目前,FDA认为根据其批准的适应症使用紫杉醇药物洗脱球囊和紫杉醇洗脱支架的受益依旧大于风险。


点评


Meta分析的编辑认为晚期紫杉醇毒性可能是导致观察到的死亡率增加的原因。与用于癌症化疗的溶剂型静脉注射紫杉醇(半衰期约为6小时)相比,外周药物洗脱DCB或DES上的紫杉醇半衰期为数周至数月(具体取决于所应用的生产工艺)。虽然紫杉醇结晶度有助于实现更高的组织摄取和保留,并改善生物效应,但可能会导致下游循环系统中栓塞微粒的形成。相关动物研究已经证实了会导致下肢骨骼肌小血管栓塞。对紫杉醇药物洗脱球囊,只有1%到10%的紫杉醇剂量被转移到目标血管壁,多达90%的紫杉醇晶体进入到系统循环中。但紫杉醇DES患者远端紫杉醇栓塞率(如有)仍不清楚。


大家认为该Meta分析目前有几个局限性:


首先,该研究未纳入膝下动脉患者的研究数据,这些患者的病情与急性下肢缺血患者有明显不同,他们的死亡率相对较低。


第二,由于产品的特殊性,这类临床试验几乎无法采用双盲。由于研究者均知晓受试者的治疗情况,这就导致在受试者治疗及护理过程中,研究者可能会潜在的受分组影响。比如,给予对照组受试者更多的临床关注、更多的医学健康教育、更多的生活习惯引导等等。


第三,当患者出现下肢动脉闭塞时,也就预示着其冠状动脉的情况也不佳。患者的生活习惯对于疾病的进展有很大影响。虽然试验多采用单盲,但并不能保证所有受试者不会从其他途径知晓自己的分组情况,且一般临床试验的观察周期为一年,一年以后受试者可能均已知晓自己的分组情况。比如试验组的受试者知晓自己的治疗后放弃了对不良生活习惯的改变,而对照组的受试者则选择更佳的生活习惯。而生活习惯是非常难以收集,且是难以定量分析的变量,大家看到的许多研究都没有对生活习惯进行分析。


第四,多数研究都体现受试者的基线水平基本均衡,但在一些研究中,紫杉醇组患者合并症(如吸烟、高脂血症、高压或糖尿病)发生率在数字上更高。而生活史、疾病史的基线收集正如上面所述,可能不存在比较客观的定量评价标准。因此,可能无法深入探讨未检测到的异质性来源。


第五,根据《2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)》的推荐,对于血管腔内治疗后的下肢动脉疾病患者术后双联抗血小板治疗至少1个月。目前多数研究的双联抗血小板治疗周期是1~3个月。治疗周期结束后受试者是否还会自行服用双联抗血小板治疗,或者根据医嘱再延长双联抗血小板治疗不得而知,而双联抗血小板治疗的使用对临床结局有较大的影响。此外,下肢动脉疾病患者常常合并冠心病、高血压、高血脂、糖尿病,这些基础疾病的治疗也会影响临床结局,然而这也是多数研究存在的缺陷。


第六,研究分析的是全因死亡率,除了少数研究外,大多数研究没有报告死亡的实际原因,无法推断死因与紫杉醇使用的潜在因果关系。


该警示信会对这类产品的未来上市推广产生一定的影响,但大家还是应理性看待该警示信。任何研究都会存在一定的研究偏倚,该偏倚可能会影响试验结论。该警示信可能会促使中国的药事监管部门加强对这类产品上市后的随访工作,有可能会要求申办方定期提交上市随访结果。并根据《医疗器械不良事件监测和再评价管理办法》、《上市许可持有人个例医疗器械不良事件收集和报告引导原则》等一系列法规的要求提交医疗器械不良事件监测结果。


基于上述内容,大家依旧对紫杉醇药物洗脱球囊或洗脱支架的未来充满期待,但也希翼相关企业加强产品上市后监测工作。


上述言论仅代表个人观点。


风险警示信全文

Treatment of Peripheral Arterial Disease with Paclitaxel-Coated Balloons and Paclitaxel-Eluting Stents Potentially Associated with Increased Mortality - Letter to Health Care Providers


January 17, 2019


Dear Peripheral Interventionalists and Vascular Medicine Physicians:


We are writing to inform you that the FDA is evaluating recent information regarding the potential for increased long-term mortality after use of paclitaxel-coated balloons and paclitaxel-eluting stents to treat peripheral arterial disease (PAD) in the femoropopliteal artery.


A recent meta-analysis of randomized trials published in the Journal of the American Heart Association (JAHA) suggests a possible increased mortality rate after two years in PAD patients treated with paclitaxel-coated balloons and paclitaxel-eluting stents compared to patients treated with control devices (non-coated balloons or bare metal stents). The specific cause for this observation is yet to be determined.


BACKGROUND


Paclitaxel-coated balloons and paclitaxel-eluting stents are intended to treat de novo or restenotic lesions in the femoropopliteal artery. The balloon and stent work to mechanically open the obstructed vessel. Paclitaxel is released from the balloon or stent to prevent scar tissue formation in the blood vessel that can re-obstruct the artery (restenosis).


In the U.S., paclitaxel-coated balloons are also marketed for the treatment of stenotic lesions in dysfunctional native arteriovenous dialysis fistulae. While paclitaxel-coated stents have been approved for use in the treatment of coronary artery disease, no paclitaxel-coated balloons or paclitaxel-eluting stents are currently marketed for this use.


RECOMMENDATIONS


The FDA recommends that health care providers:


Continue surveillance of patients who have been treated with paclitaxel-coated balloons and paclitaxel-eluting stents per the current standard of care.


In clinical decision-making, discuss the risks and benefits of all available treatment options for PAD with your patients.


Report any adverse events or suspected adverse events experienced with the use of paclitaxel-coated balloons and paclitaxel-eluting stents. Voluntary reports can be submitted through MedWatch, the FDA Safety Information and Adverse Event Reporting program. Device manufacturers and user facilities must comply with the applicable Medical Device Reporting (MDR) regulations. Health care personnel employed by facilities that are subject to FDA's user facility reporting requirements should follow the reporting procedures established by their facilities. Prompt reporting of adverse events can help the FDA identify and better understand the risks associated with medical devices.


FDA ACTIONS


The FDA is currently evaluating available long-term follow-up data to determine if there are any long-term risks associated with paclitaxel-coated products. This will include an evaluation of long-term follow-up data from studies that supported approval of paclitaxel-coated balloons or paclitaxel-eluting stents in the U.S. and other available data sets. This review will focus on causes of death, the paclitaxel dose delivered, and patient characteristics that may impact clinical outcomes. Additional statistical analyses will be performed to clarify the presence and magnitude of any long-term risks. We are working with manufacturers of paclitaxel-coated balloons and paclitaxel-eluting stents to better understand this issue.


There are a number of paclitaxel-coated balloons or paclitaxel-eluting stents approved or under study for peripheral vascular use in the U.S. Currently, the FDA believes that the benefits continue to outweigh the risks for approved paclitaxel-coated balloons and paclitaxel-eluting stents when used in accordance with their indications for use.


The FDA will communicate with the public as new information becomes available.


原文链接

https://www.fda.gov/MedicalDevices/Safety/LetterstoHealthCareProviders/ucm629589.htm


文献链接

https://www.ahajournals.org/doi/10.1161/JAHA.118.011245


编辑:广州奥咨达医疗器械技术股份有限企业医学部


Hi,are you ready?

准备好开始了吗?
那就与大家取得联系吧

有一个医疗器械项目想和大家谈谈吗?您可以填写右边的表格,让大家了解您的项目需求,这是一个良好的开始,大家将会尽快与你取得联系。当然也欢迎您给大家写信或是打电话,让大家听到你的声音!

奥咨达 | 高端医疗器械临床注册专家

24小时免费咨询热线:

400-6768632

填写您的项目信息

填写完表单后,请点击以下任意一种沟通方式:

?

必赢亚娱乐官网|必赢亚娱乐官网

XML 地图 | Sitemap 地图