美国首个市售经导管主动脉瓣置换装置上市后效果较好

在美国心脏协会(AHA)年会上，美国胸外科医师协会(STS)主席Michael J. Mack医生报告指出，STS/美国心脏病学院经导管瓣膜治疗(TVT)注册研究得出的有关美国首个市售经导管主动脉瓣置换(TAVR)装置的上市后结果与随机研究和国际注册研究结果具有可比性。该研究结果同时发表于《美国医学会杂志》(JAMA 2013;310:2069-77. doi:10.1001/jama/2013.282043)。

Edwards LifeSciences公司的Sapien XT瓣膜在7710例TAVR患者中的成功植入率为92%，2/3通过经股动脉入路植入。主要终点即院内全因死亡率和卒中发生率分别为5.5%和2%。

仅1%的患者需改为接受开放性心脏手术，但开放性心脏手术与49%的院内死亡率相关。虽然总体上缺乏经验并且使用较大鞘输送系统，但大出血和血管并发症发生率相对较低，分别为3.5%和6.4%。急性肾功能不全发生率为5.5%。在3113例接受充分随访的患者中，30天死亡和卒中发生率分别为7.6%和2.8%。大部分死亡为非心血管源性。

这项TVT研究涉及2011年11月至2013年5月在224个注册医院进行TAVR的1559例不能手术的患者和6151例可手术的高危患者。患者的STS预测手术死亡风险(PROM)差异较大，介于1.2%至17.4%，中位数为7%。患者的中位年龄为84岁。

Mack医生承认，总体而言，注册研究中的患者的风险低于随机研究和欧洲研究，这可能是其获得较好结果的原因。在关键PARTNER研究中，不能手术的患者和可手术的高危患者的平均PROM分别为11.2%和11.8%。Sapien XT瓣膜获得批准正是基于关键PARTNER研究的结果。

注册研究取得较好结果的原因包括：1）可能在风险的计算中录入了不完整的数据；2）“风险蠕变”；3）手术风险较低的患者接受创伤性较小的手术；4）因国际合作，美国的学习曲线较短；5）注册研究纳入至少35个具有丰富经验的PARTNER研究中心；6）瓣膜生产商雇用临床专家在所有手术期间对术者进行强制培训。

在2011年德国主动脉瓣注册研究中，经股动脉入路组和经心尖入路组的院内死亡率分别为5.1%和7.7%。在PARTNER研究中，经股动脉入路组不能手术的患者和可手术的高危患者的30天死亡率分别为5%和3.7%，经心尖入路组可手术的高危患者的30天死亡率为8.7%。这与TVT研究中相应的30天死亡率(分别为6.1%、4.6%和9.8%)相当。

TVT注册研究纳入2012年5月期间进行的TAVR手术的88%，此时医疗保险和医疗补助服务中心宣布将全美TAVR病例纳入保险范围，同时也是研究结束的时候。

Mack医生表示，需要更完整的30天和1年长期转归信息，以更全面地评估美国的TAVR治疗结果。此外，还将探讨患者的健康状态和生活质量。目前为止，已知有63%的患者出院回家，6%新发房颤，6.6%需要新的永久性起搏器或植入式心律转复除颤器。

该研究获美国心脏病学会基金会(ACCF)和STS资助。Mack医生声明无经济利益冲突。一位研究者声明从STS获得差旅费，另一位研究者是杨森、勃林格殷格翰和赛诺菲公司的顾问。

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By: PATRICE WENDLING, Cardiology News Digital Network

Postmarket outcomes with the first commercially available U.S. transcatheter aortic valve replacement device are comparable with randomized trial and international registry experience, national registry results suggest.

The Edwards LifeSciences Sapien XT valve was successfully implanted in 92% of 7,710 TAVR patients, two-thirds with a transfemoral approach.

The primary outcomes of in-hospital all-cause mortality and stroke were 5.5% and 2%, respectively, Dr. Michael J. Mack reported at the American Heart Association scientific sessions.

Conversion to open-heart surgery was needed in only 1% of patients, but associated with a 49% incidence of in-hospital mortality.

Major bleeding and vascular complications were relatively low, at 3.5% and 6.4%, respectively, despite the overall lack of experience and use of larger sheath delivery systems. Acute renal insufficiency occurred in 5.5% of patients.

The 30-day death and stroke rates were 7.6% and 2.8% among 3,113 patients with sufficient follow-up. Most deaths were due to noncardiovascular causes, he noted.

This is the first public report from the national Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry, and comes amid calls for increased postmarket surveillance of high-risk medical devices.

The results also help address whether outcomes after a controlled commercial rollout of the first-generation valve hold up to those from clinical trials and the global TAVR experience, now based on second- and third-generation devices, according to Dr. Mack, past STS president and director of cardiovascular research and medicine at the Heart Hospital Baylor Plano in Plano, Texas.

The Food and Drug Administration initially approved the Edwards valve for severe, symptomatic aortic stenosis in inoperable patients in 2011 and expanded its label in September 2012 to include operable, high-risk patients using either a transfemoral or transapical approach.

The TVT analysis comprised 1,559 inoperable and 6,151 high-risk, operable patients who underwent TAVR at 224 participating registry hospitals from November 2011 to May 2013. Their median STS predicted risk of operative mortality (PROM) was 7%, but varied widely from 1.2% to 17.4%. Their median age was 84 years.

The risk profile of patients was generally lower in the registry than in randomized trials and European reports, and may have contributed to the good outcomes, Dr. Mack acknowledged. The mean PROM was 11.2% among inoperable patients and 11.8% among high-risk, operable patients in the pivotal PARTNER trial, which was used for the device’s approval.

Although incomplete data may have been entered into the risk calculator, the other plausible explanation is "risk creep," or that patients with lower surgical risk are being treated with the less-invasive procedure, leading to better outcomes, he noted.

Other possible contributors to the registry outcomes include a shorter U.S. learning curve due to international collaboration, inclusion of at least 35 highly experienced PARTNER study centers in the registry, and mandated training by the manufacturer including a company employed clinical specialist during all procedures.

Still, the results stack up well. Germany, which has led the TAVR revolution, had an in-hospital mortality of 5.1% with a transfemoral approach and 7.7% with a transapical approach in 2011 in the German Aortic Valve Registry.

In the PARTNER trial, 30-day mortality was 5% among inoperable patients, 3.7% among high-risk, operable patients by a transfemoral approach, and 8.7% among high-risk, operable patients by a transapical approach.

This compares with 30-day mortality rates of 6.1%, 4.6%, and 9.8%, respectively, in the TVT registry, Dr. Mack reported.

The TVT registry captured an estimated 88% of TAVR procedures performed between May 2012, when the Centers for Medicare and Medicaid Services issued its national coverage determination, and the end of the study. Notably, 30-day outcomes were reported from only 114 hospitals or 51% of the 244 hospitals in the registry. The results were published simultaneously with Dr. Mack’s presentation (JAMA 2013;310:2069-77. doi:10.1001/jama/2013.282043).

More complete long-term outcomes at 30 days and 1 year are needed to have a more comprehensive assessment of TAVR outcomes in the United States, Dr. Mack cautioned. Patient health status and quality of life outcomes will also be addressed in subsequent reports.

So far, it’s known that most (63%) patients were discharged home, 6% experienced new-onset atrial fibrillation, and 6.6% needed a new permanent pacemaker or implantable cardioverter-defibrillator.

The study was funded by the American College of Cardiology Foundation and the Society of Thoracic Surgeons. Dr. Mack reported no other disclosures; a co-author reported travel support from the STS and a second reported consulting for Janssen, Boehringer Ingelheim, and Sanofi.