Ouriel K, Veith F J, Sasahara A A
Department of Surgery, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
N Engl J Med. 1998 Apr 16;338(16):1105-11. doi: 10.1056/NEJM199804163381603.
Recent controlled trials suggest that thrombolytic therapy may be an effective initial treatment for acute arterial occlusion of the legs. A major potential benefit of initial thrombolytic therapy is that limb ischemia can be managed with less invasive interventions.
In this randomized, multicenter trial conducted at 113 North American and European sites, we compared vascular surgery (e.g., thrombectomy or bypass surgery) with thrombolysis by catheter-directed intraarterial recombinant urokinase; all patients (272 per group) had had acute arterial obstruction of the legs for 14 days or less. Infusions were limited to a period of 48 hours (mean [+/-SE], 24.4+/-0.86), after which lesions were corrected by surgery or angioplasty if needed. The primary end point was the amputation-free survival rate at six months.
Final angiograms, which were available for 246 patients treated with urokinase, revealed recanalization in 196 (79.7 percent) and complete dissolution of thrombus in 167 (67.9 percent). Both treatment groups had similar significant improvements in mean ankle-brachial blood-pressure index. Amputation-free survival rates in the urokinase group were 71.8 percent at six months and 65.0 percent at one year, as compared with respective rates of 74.8 percent and 69.9 percent in the surgery group; the 95 percent confidence intervals for the differences were -10.5 to 4.5 percentage points at six months (P=0.43) and -12.9 to 3.1 percentage points at one year (P=0.23). At six months the surgery group had undergone 551 open operative procedures (excluding amputations), as compared with 315 in the thrombolysis group. Major hemorrhage occurred in 32 patients in the urokinase group (12.5 percent) as compared with 14 patients in the surgery group (5.5 percent) (P= 0.005). There were four episodes of intracranial hemorrhage in the urokinase group (1.6 percent), one of which was fatal. By contrast, there were no episodes of intracranial hemorrhage in the surgery group.
Despite its association with a higher frequency of hemorrhagic complications, intraarterial infusion of urokinase reduced the need for open surgical procedures, with no significantly increased risk of amputation or death.
近期的对照试验表明，溶栓治疗可能是治疗急性下肢动脉闭塞的一种有效的初始治疗方法。初始溶栓治疗的一个主要潜在益处是，可通过侵入性较小的干预措施来处理肢体缺血问题。
在这项在113个北美和欧洲地点进行的随机、多中心试验中，我们将血管手术（如血栓切除术或搭桥手术）与通过导管定向动脉内注射重组尿激酶进行溶栓治疗进行了比较；所有患者（每组272例）下肢急性动脉阻塞均在14天以内。输注时间限制在48小时（平均值[±标准误]，24.4±0.86），之后如有需要，通过手术或血管成形术纠正病变。主要终点是6个月时的无截肢生存率。
246例接受尿激酶治疗的患者的最终血管造影显示，196例（79.7%）再通，167例（67.9%）血栓完全溶解。两个治疗组的平均踝臂血压指数均有类似的显著改善。尿激酶组6个月时的无截肢生存率为71.8%，1年时为65.0%，而手术组分别为74.8%和69.9%；差异的95%置信区间在6个月时为-10.5至4.5个百分点（P=0.43），在1年时为-12.9至3.1个百分点（P=0.23）。6个月时，手术组进行了551例开放性手术（不包括截肢），而溶栓组为315例。尿激酶组有32例患者（12.5%）发生大出血，而手术组有14例患者（5.5%）（P=0.005）。尿激酶组有4例颅内出血（1.6%），其中1例致命。相比之下，手术组无颅内出血事件。
尽管动脉内输注尿激酶与出血并发症的发生率较高相关，但它减少了开放性手术的需求，截肢或死亡风险没有显著增加。
