Section of Cardiology, University of Washington, Seattle.
Duke Clinical Research Institute, Durham, North Carolina.
JAMA Cardiol. 2017 Aug 1;2(8):846-854. doi: 10.1001/jamacardio.2017.1685.
Transcatheter aortic valve replacement (TAVR) was approved by the US Food and Drug Administration for severe aortic stenosis in patients who cannot undergo surgery and for patients at high operative risk. Use of TAVR for off-label indications has not been previously reported.
To evaluate patterns and adverse outcomes of off-label use of TAVR in US clinical practice.
DESIGN, SETTING AND PARTICIPANTS: Patients receiving commercially funded TAVR in the United States are included in the Transcatheter Valve Therapy Registry. A total of 23 847 patients from 328 sites performing TAVR between November 9, 2011, and September 30, 2014, were assessed for this study. Off-label TAVR was defined as TAVR in patients with known bicuspid valve, moderate aortic stenosis, severe mitral regurgitation, severe aortic regurgitation, or subaortic stenosis. Data were linked with the Centers for Medicare & Medicaid Services for 15 397 patients to evaluate 30-day and 1-year outcomes.
Off-label use of TAVR.
Frequency of off-label TAVR use and the association with in-hospital, 30-day, and 1-year adverse outcomes.
Among the 23 847 patients in the study (11 876 women and 11 971 men; median age, 84 years [interquartile range, 78-88 years]), off-label TAVR was used in 2272 patients (9.5%). In-hospital mortality was higher among patients receiving off-label TAVR than those receiving on-label TAVR (6.3% vs 4.7%; P < .001), as was 30-day mortality (8.5% vs 6.1%; P < .001) and 1-year mortality (25.6% vs 22.1%; P = .001). Adjusted 30-day mortality was higher in the off-label group (hazard ratio, 1.27; 95% CI, 1.04-1.55; P = .02), while adjusted 1-year mortality was similar in the 2 groups (hazard ratio, 1.11; 95% CI, 0.98-1.25; P = .11). The median rate of off-label TAVR use per hospital was 6.8% (range, 0%-34.7%; interquartile range, 3.4%-12.1%), with hospitals in the highest tertile of off-label use associated with increased 30-day adverse cardiovascular events compared with the lowest tertile. However, this difference was not observed in adjusted 30-day or 1-year outcomes.
Approximately 1 in 10 patients in the United States have received TAVR for an off-label indication. After adjustment, 1-year mortality was similar in these patients to that in patients who received TAVR for an on-label indication. These results reinforce the need for additional research on the efficacy of off-label TAVR use.
经美国食品和药物管理局批准，经导管主动脉瓣置换术（TAVR）可用于不能接受手术的严重主动脉瓣狭窄患者和高手术风险患者。此前尚未报告 TAVR 用于标签外适应证的情况。
评估美国临床实践中 TAVR 标签外使用的模式和不良结局。
设计、地点和参与者：本研究纳入了在美国接受商业资助 TAVR 的患者。对 2011 年 11 月 9 日至 2014 年 9 月 30 日期间在 328 个地点进行的 23847 例患者进行了评估。将 TAVR 用于已知二叶瓣、中度主动脉瓣狭窄、严重二尖瓣反流、严重主动脉瓣反流或主动脉瓣下狭窄的患者定义为 TAVR 标签外使用。将数据与医疗保险和医疗补助服务中心（Centers for Medicare & Medicaid Services）进行了关联，以评估 30 天和 1 年的结局。
TAVR 标签外使用。
标签外 TAVR 使用的频率及其与住院、30 天和 1 年不良结局的相关性。
在这项研究的 23847 例患者中（11876 例女性和 11971 例男性；中位年龄 84 岁[四分位距，78-88 岁]），2272 例（9.5%）患者接受了标签外 TAVR。与接受标签内 TAVR 的患者相比，接受标签外 TAVR 的患者院内死亡率更高（6.3%比 4.7%；P < .001），30 天死亡率（8.5%比 6.1%；P < .001）和 1 年死亡率（25.6%比 22.1%；P = .001）也更高。标签外组校正后 30 天死亡率更高（风险比，1.27；95%CI，1.04-1.55；P = .02），而校正后 1 年死亡率在两组间相似（风险比，1.11；95%CI，0.98-1.25；P = .11）。每个医院标签外 TAVR 使用的中位数为 6.8%（范围，0%-34.7%；四分位距，3.4%-12.1%），与最低三分位相比，最高三分位的医院与 30 天不良心血管事件风险增加相关。然而，在调整后的 30 天或 1 年结局中并未观察到这种差异。
在美国，大约每 10 例患者中就有 1 例接受了 TAVR 标签外适应证的治疗。调整后，这些患者的 1 年死亡率与接受标签内 TAVR 适应证治疗的患者相似。这些结果强调了需要进一步研究 TAVR 标签外使用的疗效。
