血栓抽吸对STEMI患者无生存益处

欧洲心脏病学会(ESC)年会上公布的TASTE随机研究显示，与单纯进行经皮冠状动脉介入治疗(PCI)相比，PCI前进行人工血栓抽吸对ST段抬高型心肌梗死(STEMI)患者的早期死亡率无显著益处。这项研究同期发表在《新英格兰医学杂志》上(N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1308789])。

在7,244例STEMI患者中，血栓抽吸+PCI组和单纯PCI组的30天全因死亡率(主要终点)分别为2.8%和3.0%，差异不显著。按方案分析也得出相似结果(2.6% vs. 2.9%)。此外，血栓抽吸对所有预设的次要终点均无显著影响。


Ole Fröbert医生

在这项研究中，瑞典厄勒布鲁大学医院心脏病科的Ole Fröbert医生及其同事从瑞典冠状动脉造影和血管成形术在线注册库(SCAAR)纳入7244例STEMI或左束支传导阻滞患者，并按1:1随机分入人工血栓抽吸+PCI组和单纯PCI组。血小板抑制剂或抗凝剂的使用由医生决定。SCAAR是SWEDEHEART注册研究的一部分，后者从瑞典所有29个冠状动脉介入治疗中心、1个冰岛中心和1个丹麦中心连续纳入患者。

结果显示，30天时，抽吸+PCI组和单纯PCI组的支架内血栓形成率(0.2% vs. 0.5%)、靶病变血运重建率(1.2% vs. 1.6%)和靶血管血运重建率(1.8% vs. 2.2%)相似。

虽然近期对21项随机试验进行荟萃分析发现，进行直接血管成形术的STEMI患者的血栓切除术相关卒中风险趋于增加(Int. J. Cardiol. 2013;166:606-12)，但出院时的卒中和神经系统并发症发生率相同，均为0.5%(19起事件 vs. 18起事件；比值比 1.06；P=0.87)。

亚组分析显示，所有预设亚组的30天死亡率结果一致，这些亚组包括高危患者，如心肌梗死溶栓(TIMI)血流0或1级、血栓4或5级(5分制量表)和吸烟的患者。

然而，当前结果与其他研究结果不一致，这包括2010年Fröbert医生发表的一项研究，后者在瑞典人群中发现血栓抽吸组校正后的死亡率高于单纯PCI组(Int. J. Cardiol. 2010;145:572-3)。

研究结果的不一致可归因于随访、症状持续时间、参与中心数量方面的差异以及机械血栓切除器械劣于人工抽吸导管的结果。此外，INFUSE-AMI试验 表明，溶栓药物可能更有效。

在随刊述评中，慕尼黑工业大学德国心脏中心的Robert A. Byrne医生和Adnan Kastrati医生表示，基于当前的TASTE结果，既往临床研究观察到的血栓抽吸对死亡率的益处可能为偶然性观察结果(N. Engl. J. Med. 2013 [doi:10.1056/NEJMe1310361])。

然而，许多心血管介入医生争议TASTE研究结果并未完全排除血栓抽吸存在潜在益处的可能性，因此仍将继续进行血栓抽吸。随刊述评专家和Fröbert医生均认为有必要对12个月时的终点进行分析，因为单中心TAPAS研究直至随访12个月时才观察到显著死亡率获益。此外，TASTE研究中的血栓抽吸组再梗死率比单纯PCI组低40%，TAPAS研究中这一效应量在1年时具有显著性。

在第二篇随刊述评中，美国国立心肺和血液研究所心血管科主任Michael S. Lauer医生和波士顿大学数学/统计学、生物统计学和流行病学教授Ralph D’Agostino Sr.博士表示，TASTE试验仍被视为在设计和低成本方法方面具有突破性，这可潜在使我们从随机研究与注册研究的无尽争论中解脱出来。两人认为需克服许多障碍，包括在卫生保健和临床数据零散且质量低的地区进行随机注册研究，但也指出，在存在注册库和其他强大数字平台的情况下，社会无法再动用数千万或数亿美元的资金来进行随机有效性研究。目前采用大量数据和小预算来设计和进行大型研究是可行的，但我们也必须认识到要做到这一点的话，需要不同群体的研究者和利益相关者克服许多棘手的挑战才行(N. Engl. J. Med. 2013 [doi:10.1056/NEJMe1310102])。

TASTE获瑞典研究理事会和瑞典地方政府和地区协会资助。 Fröbert医生声明从泰尔茂等公司获得无限制资金，并担任Stentys和百多力公司顾问。其他研究者声明与多家研究和商业机构存在利益关系。Lauer医生、D’Agostino医生和 Byrne医生声明无相关经济利益冲突。Kastrati医生声明从百多力等多家公司获得酬金。

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By: PATRICE WENDLING, Cardiology News Digital Network

Manual thrombus aspiration before percutaneous coronary intervention provided no significant benefit to early mortality over PCI alone in patients with ST-segment elevation myocardial infarction in the registry-based, randomized TASTE trial.

Among 7,244 patients with STEMI, the primary endpoint of all-cause mortality at 30 days was 2.8% with thrombus aspiration plus PCI and 3.0% with PCI alone, a nonsignificant difference. The per-protocol analysis was also similar, at 2.6% and 2.9%, respectively.

Further, there was no significant effect of thrombus aspiration on any of the prespecified secondary outcomes, according to results presented at the annual congress of the European Society of Cardiology by Dr. Ole Fröbert and simultaneously published online (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1308789]).

The multicenter TASTE (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) trial provides intriguing results, but is unlikely to settle the debate over the benefits of using manual thrombus aspiration in this setting.

Based on the current TASTE results, the mortality benefit observed with thrombus aspiration in earlier clinical trials "may have been a chance finding," interventional cardiologists Dr. Robert A. Byrne and Dr. Adnan Kastrati, with the German heart center, Technical University of Munich, wrote in an accompanying editorial (N. Engl. J. Med. 2013 [doi:10.1056/NEJMe1310361]).

However, "many interventional cardiologists will continue to perform thrombus aspiration for now, contending that the results of the TASTE trial do not entirely exclude the possibility of a potential benefit of the procedure."

The editorialists, as well as Dr. Fröbert, pointed to the need for an updated analysis of outcomes at 12 months since it wasn’t until 12 months of follow-up that a significant mortality benefit emerged in the single-center Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS).

In addition, the reinfarction rate in TASTE was 40% lower with thrombus aspiration, and this magnitude of effect was significant at 1 year in TAPAS, said Dr. Fröbert of the department of cardiology, Örebro (Sweden) University Hospital.

The TASTE investigators enrolled 7,244 participants with STEMI or left bundle branch block from the online national Swedish Coronary Angiography and Angioplasty Registry (SCAAR), and randomized them 1:1 to manual thrombus aspiration followed by PCI or PCI alone. The use of platelet inhibitors or anticoagulants was at physician discretion.

SCAAR is part of the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry of consecutive patients from all 29 Swedish coronary intervention centers and 1 Icelandic center. An additional center in Denmark was also included in the trial.

At 30 days, the aspiration-plus-PCI and PCI-only groups had similar rates of stent thrombosis (0.2% vs. 0.5%), target lesion revascularization (1.2% vs. 1.6%), and target vessel revascularization (1.8% vs. 2.2%), Dr. Fröbert reported.

Although a recent meta-analysis of 21 randomized trials identified a trend toward a higher risk of stroke with thrombectomy in STEMI patients undergoing primary angioplasty (Int. J. Cardiol. 2013;166:606-12), stroke and neurologic complications at discharge were identical at 0.5% (19 events vs. 18 events; odds ratio,1.06; P = .87).

In subgroup analyses, the results for 30-day mortality were consistent across all prespecified subgroups, including high-risk patients such as those with a TIMI (Thrombolysis in Myocardial Infarction) flow grade 0 or 1, thrombus grade 4 or 5 on a 5-point scale, and smokers, Dr. Fröbert reported.

The current results contrast with those of other studies, however, including a 2010 report by Dr. Fröbert showing higher mortality, after adjustment, with thrombus aspiration than PCI alone among a Swedish population (Int. J. Cardiol. 2010;145:572-3).

The inconsistent findings may be attributable to differences in follow-up, duration of symptoms, number of participating centers, and the finding that mechanical thrombectomy devices may be inferior to manual aspiration catheters, he noted in the article. Clot-busting drugs may also be more effective, as suggested by the INFUSE-AMI trial.

Further insights are expected from another larger manual thrombectomy trial, TOTAL, with a composite end point of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or new or worsening heart failure at 180 days.

Still, the TASTE trial is being heralded for its design and low-cost approach as a breakthrough in research that "can potentially release us from the circular (and expensive) trap of the randomized-versus-registry debate," wrote Dr. Michael S. Lauer, director, division of cardiovascular sciences, National Heart, Lung, and Blood Institute and Ralph D’Agostino Sr., Ph.D., professor of mathematics/Statistics, biostatistics, and epidemiology, Boston University, in a second editorial accompanying the study (N. Engl. J. Med. 2013 [doi:10.1056/NEJMe1310102]).

They acknowledged that a variety of hurdles must be overcome, including undertaking randomized registry trials in places where health care and clinical data are fragmented and of lower quality, but also that society can no longer afford to undertake randomized effectiveness trials that cost tens or hundreds of millions of dollars at a time when registries and other powerful digital platforms are available.

"Today it may be possible to design and conduct megatrials with what we have: bigger data and smaller budgets," they wrote. "Yet we must also recognize and acknowledge the daunting challenges that diverse groups of researchers and stakeholders must overcome to get there."

TASTE was funded by the Swedish Research Council and Swedish Association of Local Authorities and Regions. Dr. Fröbert also reported unrestricted grants from Terumo, Medtronic, and Vascular Solutions, and consultancy for Stentys and Biotronik. His coauthors reported financial ties with numerous research and commercial entities. Dr. Lauer, Dr. D’Agostino, and Dr. Byrne reported having no relevant financial conflicts. Dr. Kastrati reported receiving fees from Biotronik, the Medicines, Astra-Zeneca, MSD, St. Jude Medical, and Biosensors.