The Safety of Paclitaxel-Coated Devices for Patients with Peripheral Artery Disease.
The Safety of Paclitaxel-Coated Devices for Patients with Peripheral Artery Disease.
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DOI：
10.1007/s11886-021-01477-4
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发表时间：
2021-03-18
影响因子：
3.7
通讯作者：
Secemsky EA
中科院分区：
文献类型：
--
作者：
Krawisz AK;Secemsky EA
外周动脉疾病 (PAD) 是一种常见的、使人衰弱的疾病，影响着 850 万美国人，且预后不良。下肢 PAD 最常见的表现是跛行，这种情况会显着降低生活质量和功能状态。相对于裸金属支架 (BMS) 和经皮腔内血管成形术 (PTA)，紫杉醇涂层球囊和支架（PCB 和 PES）代表了治疗难治性患者能力的突破，因为它们提高了初次通畅率，减少了目标病变血运重建（TLR），并最大限度地减少了股腘病变的晚期管腔丢失。结果，紫杉醇涂层装置（PCD）迅速成为股腘动脉疾病血运重建的护理标准。最近对汇总数据的荟萃分析表明，相对于未涂层装置，使用紫杉醇涂层装置治疗的患者存在晚期死亡信号。这对血管群和 PAD 患者的治疗产生了重大影响。在此，我们详细回顾了与紫杉醇相关的晚期死亡率信号的现有数据。 2018 年 12 月，Katsanos 等人。 J Am Heart Assoc 7: e011245, 2018) 发表了随机对照试验 (RCT) 的数据，这些试验表明，与使用未涂层装置治疗的患者相比，接受涉及股腘动脉段的 PCD 治疗的患者在 2 年和 5 年的死亡率有所增加。根据这项分析，随机试验被停止，FDA 致信医疗保健提供者，建议限制再狭窄风险最高的患者使用这些设备。随着支持这些设备安全性的更多数据出现，FDA 组织了一次咨询委员会会议来审查可用数据并确定前进的道路。 FDA 的结论是，没有足够的数据来就 PCD 的安全性做出最终决定。他们允许这些设备继续留在市场上，但修改了安全标签，并更新了致医疗保健提供者的信函，以继续限制对再次干预风险最高的患者使用。 FDA 还要求提供额外的长期数据，包括随机对照试验和真实世界数据。迄今为止，已经对临床试验数据、长期随访的随机对照试验以及大型观察性研究进行了更新的患者水平荟萃分析。虽然使用重叠临床试验数据进行的荟萃分析发现，接受 PCD 治疗的患者死亡率持续增加，但个别行业赞助的随机对照试验和大型观察性研究始终未能检测到相应的死亡率增加。迄今为止，尚未观察到紫杉醇与死亡率之间的联系机制。目前，我们正处于对紫杉醇涂层器械的长期安全性得出明确结论的僵局。当我们等待正在进行的临床试验的注册时，我们必须根据现有数据为患者的护理做出合理的决定，因为这些设备对我们的患者具有重要的临床意义。从这场争议中可以学到的一个重要教训是，对于未来的设备试验，致力于长期随访至关重要。
Peripheral artery disease (PAD) is a common, debilitating disease that impacts 8.5 million Americans and carries a poor prognosis. The most common manifestation of lower extremity PAD is claudication—a condition which significantly reduces quality of life and functional status. Paclitaxel-coated balloons and stents (PCBs and PESs) represented a breakthrough in the ability to treat medication-refractory patients relative to bare metal stents (BMSs) and percutaneous transluminal angioplasty (PTA) because they improve primary patency rates, reduce target lesion revascularization (TLR), and minimize late-lumen loss for femoropopliteal lesions. As a result, paclitaxel-coated devices (PCDs) were swiftly established as the standard of care for revascularization of femoropopliteal artery disease. A recent meta-analysis of summary-level data demonstrated a late mortality signal for patients treated with paclitaxel-coated devices relative to uncoated devices. This has had a major impact on the vascular community and for the treatment of patients with PAD. Herein, we provide a detailed review of the available data on the late mortality signal associated with paclitaxel. In December of 2018, Katsanos et al. J Am Heart Assoc 7: e011245, 2018) published data from randomized-controlled trials (RCTs) that demonstrated an increase in mortality at 2 and 5 years in patients treated with PCDs involving the femoropopliteal arterial segment relative to patients treated with uncoated devices. As a result of this analysis, randomized trials were stopped and the FDA sent a letter to healthcare providers recommending restriction of use of these devices to patients at the highest risk of restenosis. As additional data emerged supporting the safety of these devices, the FDA organized an advisory committee meeting to review the available data and to determine a pathway forward. The FDA concluded that there were insufficient data to make a final decision regarding the safety of PCDs. They allowed these devices to remain on the market, but with revised safety labeling and updated their letter to healthcare providers to continue to restrict use to patients at highest risk of reintervention. The FDA also called for additional long-term data, including from RCTs and real-world data. To date, an updated patient-level meta-analysis of clinical trial data, RCTs with longer-term follow-up, and large observational studies have been conducted. While meta-analyses conducted using overlapping clinical trial data have found a persistent increase in mortality for those treated with PCDs, individual industry-sponsored RCTs and large observational studies have consistently failed to detect a corresponding mortality increase. To date, no mechanism linking paclitaxel to mortality has been observed. We are currently at an impasse for drawing definitive conclusions regarding the long-term safety of paclitaxel-coated devices. As we await enrollment in ongoing clinical trials, we must proceed with making reasonable decisions for our patients’ care from the available data, as these devices have important clinical implications for our patients. A critical lesson that can be learned from this controversy is that, for future device trials, committing to long-term follow-up is crucial.
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DOI：
10.1016/j.ejvs.2018.10.021
发表时间：
2019-05-01
影响因子：
5.7
作者：
Behrendt, Christian-Alexander;Bischoff, Moritz S.;Riess, Henrik C.
通讯作者：
Riess, Henrik C.
影响因子：
4.3
作者：
Bradbury, Andrew W.;Adam, Donald J.;Raab, Gillian M.
通讯作者：
Raab, Gillian M.
影响因子：
4.3
作者：
Armstrong, Ehrin J.;Wu, Julie;Laird, John R.
通讯作者：
Laird, John R.
影响因子：
19.7
作者：
JOHNSTON, KW
通讯作者：
JOHNSTON, KW
影响因子：
24
作者：
Berger, Jeffrey S.;Ladapo, Joseph A.
通讯作者：
Ladapo, Joseph A.