A safety and feasibility report of combined direct thrombin and GP IIb/IIIa inhibition with bivalirudin and tirofiban in peripheral vascular disease intervention: treating critical limb ischemia like acute coronary syndrome.

BACKGROUND: 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). METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Critical limb ischemia: a global epidemic.A critical analysis of current treatment unmasks the clinical and economic costs of CLI.

BACKGROUND: Multiple reports document the higher costs of primary amputation (PA) compared to infrainguinal bypass surgery (IBS). Recent reports document 40-50% cost-effectiveness for percutaneous transluminal angioplasty (PTA) compared to IBS. The literature suggests appropriate initial treatment for critical limb ischemia (CLI) to be IBS = 38%, PTA = 28%, and PA = 16%. The encouraging 6-month Laser Angioplasty for Critical Limb Ischemia (LACI) 93% limb salvage rate prompted an independent CLI and LACI clinical and economic analysis. METHODS: Between 1999-2001 a reference amputation population (RAP) of 417 patients with at least one infrainguinal amputation were identified from a 2.5 million patients Medicare/insurance dataset. Clinical data and all medical cost claims for 18 continuous months, 12-month prior and 6-month post-amputation, were analyzed for PTA, IBS, and PA treatment pathways. Based on multiple assumptions and the LACI phase II results, economic outcomes were used for a LACI pathway analysis compared to PTA, IBS and PA pathways by substituting the LACI trial pathway as the initial treatment in lieu of the RAP actual treatment. RESULTS: Initial treatments for CLI RAP were PA = 67%, IBS = 23%, PTA = 10%; A majority of wound complications (80%) and myocardial infarction 7/9 (77.7%), stroke 13/16 (81.2%), and death 2/2 (100%) occurred in the PA RAP. Only 35% of the RAP had an ankle brachial index (ABI) and only 16% angiography before PA. 227/417 (56%) of the RAP had multiple procedures. Average total costs / patient = $31,638 without LACI and $25,373 with LACI. Average savings/patient with LACI = $6,265. CONCLUSION: The most common current treatments in the US for CLI are still characterized by high rates of primary amputations, multiple procedures, and high rates of procedure-related complications. Despite the limitations and assumptions of this analysis, the utilization of a LACI pathway first revascularization treatment strategy may provide clinical and economic cost savings in treating patients with CLI.

Novel simultaneous combination chemical thrombolysis/rheolytic thrombectomy therapy for acute critical limb ischemia: the power-pulse spray technique.

The novel power-pulse spray (P-PS) technique maximizes and combines the advantages and minimizes the disadvantages of both chemical thrombolysis (CT) and rheolytic thrombectomy (RT). Forty-nine consecutive patients with iliofemoral thrombotic occlusion were treated via P-PS technique. Using a 6 Fr RT catheter, saline prime was exchanged for thrombolytic solution [group 1, 10-20 mg tenecteplase (TNK)/50 cc saline, n = 25; group 2, 1,000,000 urokinase (UK)/50 cc saline, n = 24]. The outflow port was closed, then the catheter was advanced at 1 mm increments while pulsing lytic agent. After 30-min lysis time, RT and definitive treatment of the underlying stenosis were performed. Procedure success was 23/25 (92%) and 22/24 (91.6%) for group 1 and 2, respectively. The mean total procedure time was 72 and 75 min in group 1 and 2, respectively. Thirty-day limb salvage was 91% in both groups. There were no major surgical complications. The P-PS technique is safe and effective using either UK or TNK, offering several potential advantages over monotherapy, including more rapid revascularization, decreases systemic lytic exposure and bleeding complications while facilitating both CT and RT capacity and efficacy.

Continuous tenecteplase infusion combined with peri/postprocedural platelet glycoprotein IIb/IIIa inhibition in peripheral arterial thrombolysis: initial safety and feasibility experience.

PURPOSE: To evaluate a continuous-infusion protocol for peripheral arterial thrombolysis using tenecteplase (TNK), with regard to the technique, dosing, infusion times, and clinical outcomes. METHODS: Between November 1999 and July 2002, 48 patients (30 men; mean age 68.5+/-11.9 years) presented with acute limb ischemia (ALI) owing to iliofemoral arterial thrombosis, which was treated with continuous TNK infusion (either 0.50 mg/h [n=22, group A] or 0.25 mg/h [n=26, group B]). All patients received periprocedural heparin (500 U/h) and peri and postprocedural tirofiban for 6 to 12 hours. Follow-up included ankle-brachial index and duplex ultrasound at baseline, 1 month, and 6 months. The variables retrospectively analyzed included total infusion time, total TNK dose, fibrinogen analysis, clinical and thrombolysis outcomes, and complications. RESULTS: The overall clinical procedural success was 95.8%. Complete (>95%) lysis was observed in 35 (73%) patients; overall mean infusion time was 7.5 hours, and overall mean TNK dose was 4.8 mg. No deaths, intracranial bleeding, or embolic events occurred in either group. Of the 8 (16.7%) complications, 5 (10.4%) were major: 1 femoral repair (group A), 2 >5-cm nonsurgical hematomas (1 in each group), and 2 gastrointestinal hemorrhages (1 in each group). The 3 (6.3%) minor complications were minor hematomas (2 in group A and 1 in group B). The 30-day and 14-month mean limb salvage rates were 95.8% (46/ 48) and 89.6% (43/48), respectively. CONCLUSIONS: Continuous TNK infusion (0.25-0.50 mg/h) is a safe and feasible treatment for continuous pharmacological thrombolysis in ALI, potentially offering decreased infusion times and bleeding complications, as well as improved outcomes.

Intraoperative innominate and common carotid intervention combined with carotid endarterectomy: a "true" endovascular surgical approach.

PURPOSE: To report the technique of carotid endarterectomy (CEA) combined with retrograde balloon angioplasty and stenting of proximal "tandem" lesions in the supra-aortic trunk. TECHNIQUE: Intraoperative techniques in 34 patients with 23 left common carotid artery (CCA) and 11 innominate artery lesions included general anesthesia, low-dose dextran, prosthetic patching, selective shunting, 8-F sheath entry into the native CCA before the CEA, manual CCA sizing, and balloon-expandable stent placement after predilation. The technique has a high procedural success rate (97%) and appears durable. Over a mean 34-month follow-up, 2 >70% ostial CCA restenoses were found at 24 months. CONCLUSIONS: Intraoperative innominate or left CCA balloon angioplasty/stenting combined with carotid endarterectomy is safe, effective, and durable.

Bivalirudin as a foundation anticoagulant in peripheral vascular disease: a safe and feasible alternative for renal and iliac interventions.

BACKGROUND: Many heparin (UFH) limitations are overcome by bivalirudin (Angiomax ). The pharmacokinetic profile of bivalirudin appears well suited for percutaneous peripheral intervention (PPI), yet few data exist regarding its safety and feasibility in this setting. METHODS: One hundred and eighty renal and 75 iliac PPIs performed between May 2001 and June 2002 with bivalirudin as anticoagulation were compared to a historical UFH control. Variables evaluated included thrombotic events, intracranial bleeding, major surgical complications, sheath removal time, vascular access complication, time to ambulate and length of stay (LOS). Follow-up included 6-month renal and iliac duplex ultrasound and ankle-brachial index. RESULTS: Procedural success was achieved in 100% of patients treated with bivalirudin, with no thrombotic events, intracranial bleeding or major surgical complications observed. Procedural success was achieved in 179/180 (99%) renal and 74/75 (98.6%) iliac patients treated with UFH. Significant differences were observed for sheath removal time < 60 minutes (84% versus 59%; p < 0.0001), time to ambulation < 6 hours (75.5% versus 58%; p < 0.0005) and LOS < 24 hours (85.5% versus 72%; p = 0.002) in bivalirudin-treated renal PPI patients versus UFH-treated patients, respectively. Significant differences were also observed in favor of bivalirudin for the iliac PPIs for sheath removal time < 60 minutes (p = 0.012) and time to ambulation < 6 hours (p = 0.039). Following 6-month renal and iliac duplex ultrasound, repeat PPI was required in 7/180 (3.9%) and 9/180 (5%) of renal, and 3/75 (4%) and 4/75 (5.3%) of iliac patients treated with bivalirudin or UFH, respectively. CONCLUSION: Bivalirudin is a safe and feasible alternative anticoagulant in renal and iliac PPI and may offer decreased sheath removal time, time to ambulation and LOS. A larger prospective randomized multicenter trial is warranted.