Allie David E, Hebert Chris J, Lirtzman Mitchell D, Wyatt Charles H, Keller V Antoine, Khan Mohamed H, Khan Muhammad A, Fail Peter S, Vivekananthan Krishnamoorthy, Allie Sonja E, Mitran Elena V, Chaisson Gary, Stagg Samuel J, Allie Adam A, McElderry Michael W, Barker Esmond A, Walker Craig M
Cardiovascular Institute of the South, Houma, LA, USA.
J Invasive Cardiol. 2005 Aug;17(8):427-32.
The combination of glycoprotein (GP) IIb-IIIa inhibition and direct thrombin inhibition (DTI) with bivalirudin (Angiomax, The Medicines Company, Cambridge, Massachusetts) have shown ischemic and hemorrhagic outcomes benefit in coronary interventions and may have similar benefits in percutaneous peripheral interventions (PPI). The high incidence of diabetes, chronic renal disease, platelet dysfunction, hypercoagulability, inflammation and a thrombus-rich environment make a GP IIb-IIIa and DTI combination with tirofiban (Aggrastat Merck and Company, Inc., Whitehouse Station, New Jersey) an attractive anticoagulation strategy in the PPI treatment of critical limb ischemia (CLI).
Between May 1, 2001 and January 31, 2003, a CLI treatment group of 149 patients received PPI with bivalirudin (0.75 mg per kg bolus with 1.75 mg per kg per hour periprocedural infusion) and tirofiban (10 mcg per kg per minute bolus with 12-hour 0.1 mcg per kg per minute infusion) as an anticoagulation and antiplatelet strategy, and were compared to a matched unfractionated heparin (UFH) control group without GP IIb-IIIa inhibitors. Clinical and hemostasis outcomes were analyzed, including distal embolization (DE).
Procedural success was 95.9% and 97.3% in the UFH control group and DTI-GP IIb-IIIa group, respectively. Significant differences were observed in the sheath removal time < 2 hours (60.5% UFH group versus 19.4% DTI-GP IIb-IIIa group; p = < 0.0001). Vascular closure devices were used equally in both groups. No statistical significance was observed in major and minor complications, femoral access complications, acute (< 48 hours) or subacute (30 days) vessel thrombosis, and 6-month duplex ultrasound restenosis rate between the DTI-GP IIb-IIIa versus the UFH group. A trend towards statistical significance was observed in the 6-month secondary re-intervention and limb salvage rates (10.7% versus 18.8%; p = 0.0501 and 93.9% versus 88.5%; p = 0.053) in the DTI-GP IIb-IIIa versus the UFH group, respectively. Angiographically relevant DE occurred in 4 of 149 (1.3%) and 8 of 149 (5.4%) of the bivalirudin-tirofiban and UFH groups, respectively.
The combination of DTI with bivalirudin and GP IIb-IIIa inhibition with tirofiban is a safe and feasible alternative anticoagulation and antiplatelet strategy in PPI, and may offer improved clinical and hemostasis outcomes in treating CLI. A larger, prospective randomized trial is warranted.
糖蛋白（GP）IIb-IIIa抑制剂与比伐卢定（Angiomax，美国马萨诸塞州剑桥市医药公司）的直接凝血酶抑制（DTI）联合应用已显示在冠状动脉介入治疗中对缺血和出血结局有益，并且在经皮外周介入治疗（PPI）中可能有类似益处。糖尿病、慢性肾病、血小板功能障碍、高凝状态、炎症以及富含血栓的环境发生率较高，使得GP IIb-IIIa与替罗非班（Aggrastat，美国新泽西州白宫站默克公司）的DTI联合应用成为PPI治疗严重肢体缺血（CLI）中一种有吸引力的抗凝策略。
在2001年5月1日至2003年1月31日期间，149例CLI治疗组患者接受PPI，采用比伐卢定（0.75mg/kg静脉推注，术中每小时1.75mg/kg输注）和替罗非班（10mcg/kg每分钟静脉推注，12小时内每小时0.1mcg/kg输注）作为抗凝和抗血小板策略，并与未使用GP IIb-IIIa抑制剂的匹配普通肝素（UFH）对照组进行比较。分析临床和止血结局，包括远端栓塞（DE）。
UFH对照组和DTI-GP IIb-IIIa组的手术成功率分别为95.9%和97.3%。在鞘管拔除时间<2小时方面观察到显著差异（UFH组为60.5%，DTI-GP IIb-IIIa组为19.4%；p =<0.0001）。两组血管闭合装置的使用情况相同。在DTI-GP IIb-IIIa组与UFH组之间，主要和次要并发症、股动脉穿刺并发症、急性（<48小时）或亚急性（30天）血管血栓形成以及6个月双功超声再狭窄率方面未观察到统计学显著差异。在DTI-GP IIb-IIIa组与UFH组之间，6个月二次再干预率和肢体挽救率分别观察到有统计学显著差异的趋势（分别为10.7%对18.8%；p = 0.0501和93.9%对88.5%；p = 0.053）。血管造影相关DE在比伐卢定-替罗非班组149例中的4例（1.3%）和UFH组149例中的8例（5.4%）中发生。
DTI与比伐卢定联合以及GP IIb-IIIa与替罗非班抑制是PPI中一种安全可行的替代抗凝和抗血小板策略，并且在治疗CLI中可能提供改善的临床和止血结局。有必要进行一项更大规模的前瞻性随机试验。
