溶栓治疗可使稳定型肺栓塞患者获益

《美国医学会杂志》（JAMA）6月17日在线发表的一项荟萃分析显示，在右心室功能不全相关血流动力学稳定的肺栓塞（PE）患者中（“中危”患者），溶栓治疗可降低全因死亡率（JAMA 2014;311:2414-21）。

这项荟萃分析由纽约西奈山医疗系统圣卢克罗斯福医院中心心脏病科的Saurav Chatterjee医生及其同事进行，纳入16项涉及2115例患者的随机对照临床试验。

研究人群包括1499例右心室功能不全相关血流动力学稳定PE患者，这是临床实践中最常见到的亚组患者，并且溶栓治疗在该组患者中的风险和获益最不为人熟知。

分析结果显示，平均随访82天后，接受溶栓治疗的患者的总死亡率为2.17%，而接受抗凝治疗的患者为3.89%。此外，溶栓治疗组PE复发率（1.17%）显著低于抗凝治疗组（3.04%）。

然而，溶栓治疗组的大出血发生率为9.24%，而抗凝治疗组为3.42%。溶栓治疗组和抗凝治疗组的颅内出血发生率分别为1.46%和0.19%。

在年龄≥65岁的患者中观察到的出血风险特别高。在较年轻患者中观察到的出血风险较低，这表明年轻患者更适合接受溶栓治疗。

研究者表示，这项具有充分统计学效能的分析首次观察到溶栓治疗与PE患者有意义的死亡率降低相关。如果这些结果在未来的随机临床试验中得到证实，那么中危PE患者的溶栓治疗实践可能会发生改变。然而，在≥65岁患者中观察到大出血和颅内出血风险显著增加，这在一定程度上降低了对临床溶栓治疗优势所持的乐观。

Chatterjee医生声明无经济利益冲突，其他研究者声明与阿斯利康等多家公司存在联系。

随刊述评：溶栓治疗仍需依患者具体情况而定

波士顿布里格姆妇女医院心血管科的Joshua A. Beckman医生表示，上述分析计算了溶栓治疗的净临床获益，并且结果表明溶栓治疗在中危PE患者中有一定疗效。但结果尚不足以改变标准治疗。每位临床医生需根据患者个体情况、临床表现、合并症及医患双方对风险的耐受来决定哪些患者应接受溶栓治疗（JAMA 2014;311:2385-6）。

Beckman医生是Vascular Interventional Advances的董事会成员，并从百时美施贵宝公司获得补助金及为阿斯利康等多家公司担任顾问。

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Thrombolytic therapy decreased all-cause mortality in patients with hemodynamically stable pulmonary embolism associated with right ventricular dysfunction – those at "intermediate risk," according to a meta-analysis published online June 17 in JAMA.

The investigators described their study of 16 randomized, controlled clinical trials involving 2,115 patients as "the first analysis of thrombolysis in PE that has sufficient statistical power to detect associations with a meaningful mortality reduction." If their findings are confirmed in future randomized clinical trials, "there may be a shift in the treatment of selected patients with intermediate-risk PE using thrombolytics."

However, "the optimism regarding this clinical advantage must be tempered by [our] finding of significantly increased risk of major bleeding and intracranial hemorrhage associated with thrombolytic therapy, particularly for patients older than 65 years," said Dr. Saurav Chatterjee of the division of cardiology, St. Luke’s-Roosevelt Hospital Center of the Mount Sinai Health System, New York, and his associates (JAMA 2014;311:2414-21).

The study population included 1,499 patients who had hemodynamically stable PE associated with right ventricular dysfunction, the largest subset of patients seen in clinical practice and the group for whom the risks and benefits of thrombolysis are the most unclear.

After a mean follow-up of 82 days, overall mortality was 2.17% in patients who received thrombolysis, compared with 3.89% in those who received anticoagulation. In addition, the risk of recurrent PE was significantly lower with thrombolytic therapy (1.17%) than with anticoagulation (3.04%).

However, the rate of major bleeding was 9.24% for thrombolytic therapy, compared with 3.42% for anticoagulation. And the rate of intracranial hemorrhage was 1.46% for thrombolysis, compared with 0.19% for anticoagulation, the investigators said.

The bleeding risk was especially high in patients aged 65 years and older. Attenuation of this risk in younger patients suggests that they may be considered stronger candidates for thrombolytic therapy, Dr. Chatterjee and his associates said.

Dr. Chatterjee reported no financial conflicts; his associates reported ties to AstraZeneca, Boston Scientific, Cardiostem, Cordis, EKOS Corporation, Embolitech, GenWay, Johnson & Johnson, Soteria, and Vascular Magnetics.

Commentary: Still a case-by-case decision

Dr. Joshua A. Beckman comments: Dr. Chatterjee and his associates calculated the net clinical benefit of thrombolysis, and their result "suggests evidence of modest efficacy in intermediate-risk PE," said Dr. Joshua A. Beckman.
But their findings do not yet add up to a change in the standard of care. Each clinician must decide on an individualized basis which of these patients should receive thrombolytic therapy, based on clinical presentation, comorbid conditions, and both the physician’s and the patient’s tolerance of risk.

Dr. Beckman is in the cardiovascular division at Brigham and Women’s Hospital, Boston. He reported being a board member for Vascular Interventional Advances; receiving grant funding from Bristol-Myers Squibb; and consulting for AstraZeneca, Boston Scientific, Ferring, Merck, and Novartis. These remarks were taken from his editorial accompanying Dr. Chatterjee’s report (JAMA 2014;311:2385-6).