Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology, Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Harvard Medical School, Boston, Massachusetts.
JAMA Intern Med. 2021 Aug 1;181(8):1071-1080. doi: 10.1001/jamainternmed.2021.2738.
Paclitaxel-coated peripheral devices have been associated with increased mortality, yet this harm signal has not been replicated outside of meta-analyses of small trials.
To provide a longitudinal assessment of the safety of femoropopliteal endovascular treatment with peripheral drug-coated devices (DCDs) among Medicare beneficiaries.
DESIGN, SETTING, AND PARTICIPANTS: SAFE-PAD (Safety Assessment of Femoropopliteal Endovascular Treatment With Paclitaxel-Coated Devices) was a retrospective cohort study designed with the US Food and Drug Administration to evaluate the noninferiority of mortality between DCDs and non-drug-coated devices (NDCDs) for femoropopliteal revascularization performed in 2978 inpatient and outpatient facilities in the US from April 1, 2015, through December 31, 2018. Evaluation of the primary outcome was assessed through May 31, 2020. Participants were Medicare fee-for-service beneficiaries 66 years and older with 1 or more years of enrollment prior to femoropopliteal revascularization. Prespecified subgroups included low-risk cohorts, procedure location, disease severity, and device type. Inverse probability weighting was used to account for imbalances of observed characteristics. Sensitivity analyses were used to evaluate the potential influence of unmeasured confounding.
Treatment with DCDs vs NDCDs as determined by claims codes during the index procedure.
The primary outcome was all-cause mortality. Secondary outcomes included repeated hospitalization, repeated lower extremity revascularization, and lower extremity amputation. Falsification end points were acute myocardial infarction, congestive heart failure, and pneumonia.
Of 168 553 patients, 70 584 (41.9%) were treated with a DCD. The mean (SD) age was 77.0 (7.6) years, 75 744 (44.9%) were female, 136 916 of 167 197 (81.9%) were White individuals, 85 880 of 168 553 (51.0%) had diabetes, 82 554 of 168 553 (49.0%) used tobacco, 78 665 of 168 553 (45.7%) had critical limb ischemia (CLI), and 13 296 of 168 553 (7.9%) had a prior amputation. Median follow-up was 2.72 years (interquartile range, 0.87-3.77; longest, 5.16 years). After weighting, the cumulative incidence of all-cause mortality was 53.8% with DCDs and 55.1% with NDCDs (hazard ratio [HR], 0.95; 95% CI, 0.94-0.97; noninferiority P < .001). Cox regression and instrumental variable analyses were consistent with the primary findings. No harm associated with DCDs was observed among subgroups, including those treated with stents (HR, 0.97; 95% CI, 0.95-1.00) or balloons (HR, 0.94; 95% CI, 0.92-0.96), with or without CLI (CLI: HR, 0.95; 95% CI, 0.93-0.97; non-CLI: HR, 0.97; 95% CI, 0.95-0.99), and those within the lowest quartile of total comorbidities (HR, 0.95; 95% CI, 0.92-0.99).
In this initial report from the SAFE-PAD cohort study, DCDs were found to be noninferior to NCDCs in respect to mortality through a median follow-up of 2.72 years. This finding remained robust in sensitivity analyses and was consistent across prespecified subgroups.
紫杉醇涂层外周设备与死亡率增加有关，但这种危害信号在小型试验的荟萃分析之外并未得到复制。
在医疗保险受益人群中，提供股腘血管腔内治疗中使用外周药物涂层设备（DCD）的安全性的纵向评估。
设计、设置和参与者：SAFE-PAD（股腘血管腔内治疗中紫杉醇涂层设备的安全性评估）是一项回顾性队列研究，由美国食品和药物管理局设计，旨在评估在 2015 年 4 月 1 日至 2018 年 12 月 31 日期间，在美国 2978 家住院和门诊机构中进行的股腘血管再通术，DCD 与非药物涂层设备（NDCD）在死亡率方面的非劣效性。主要结果的评估截至 2020 年 5 月 31 日。参与者为 66 岁及以上、在股腘血管再通术之前有 1 年或以上参保的医疗保险按服务收费受益人群。预先指定的亚组包括低风险队列、手术部位、疾病严重程度和设备类型。使用逆概率加权来纠正观察特征的不平衡。敏感性分析用于评估未测量混杂因素的潜在影响。
在指数手术期间，通过索赔代码确定 DCDs 与 NDCDs 的治疗。
主要结果是全因死亡率。次要结果包括重复住院、重复下肢血运重建和下肢截肢。虚假终点为急性心肌梗死、充血性心力衰竭和肺炎。
在 168553 名患者中，70584 名（41.9%）接受了 DCD 治疗。平均（SD）年龄为 77.0（7.6）岁，75744 名（44.9%）为女性，167197 名中的 136916 名（81.9%）为白种人个体，168553 名中的 85880 名（51.0%）患有糖尿病，168553 名中的 82554 名（49.0%）使用烟草，168553 名中的 78665 名（45.7%）患有严重肢体缺血（CLI），168553 名中的 13296 名（7.9%）有既往截肢史。中位随访时间为 2.72 年（四分位间距，0.87-3.77；最长随访时间为 5.16 年）。在加权后，DCD 组的全因死亡率累积发生率为 53.8%，NDCD 组为 55.1%（风险比[HR]，0.95；95%CI，0.94-0.97；非劣效性 P<0.001）。Cox 回归和工具变量分析与主要发现一致。在亚组中未观察到与 DCD 相关的危害，包括接受支架（HR，0.97；95%CI，0.95-1.00）或球囊（HR，0.94；95%CI，0.92-0.96）治疗的患者，以及有无 CLI（CLI：HR，0.95；95%CI，0.93-0.97；非 CLI：HR，0.97；95%CI，0.95-0.99）的患者，以及总合并症最低四分位数的患者（HR，0.95；95%CI，0.92-0.99）。
在这项来自 SAFE-PAD 队列研究的初步报告中，通过 2.72 年的中位随访，发现 DCD 在死亡率方面与 NDCD 非劣效。这一发现在敏感性分析中仍然稳健，并且在预先指定的亚组中一致。
