Antithrombins In Peripheral Vascular Interventions: The Genesis Medical Center Experience

Genesis Data: UFH As the Base Anticoagulant in Peripheral Procedures Genesis Medical Center in Davenport, Iowa, is a large interventional program with 600 to 900 (average 746 cases) percutaneous cardiac procedures performed each month. Three interventionalists also perform over 400 peripheral vascular procedures each year. UFH has been used as the primary anticoagulant during these peripheral procedures. We have recently reported our in-hospital complications during PTAs with the use of unfractionated heparin as a base anticoagulant.(8) The charts of 213 consecutive PTA procedures were reviewed. Of unstaged procedures, 131 patients (57.3% males, mean age 66.4 + 12.1) met inclusion criteria. Forty-five (34.4%) of patients had recent onset of claudication and 15 (11.5%) had ulceration. Thrombus was angiographically seen and reported in 16.7% of patients. Unfractionated heparin was administered at a mean of 4672 + 1238 units (59.1 units/kg + 20.0 units/kg) during the procedure. The highest activated clotting time (ACT in seconds) during the procedure was recorded in 114 patients. ACTs were: 1. 400 seconds in 42.1% Heparin resulted in an unpredictable ACT response, as illustrated in Figure 1. In-hospital clinical events occurred in 12 (9.2%) patients who met any one of the following endpoints: “Death (0.8%), “Limb loss (1.5%), “Major bleeding (4.6%), “Emergent need for repeat revascularization of the same vessel (7.6%) “Embolic strokes (0.0%) “Vascular complications (1.5%) The best model associated for salvage revascularization included cigarette smoking within the past year, recent onset of claudication and PTA treatment below the knee. Increased dosages of UFH (units/kg) were associated with a trend toward higher rates of complications (Figure 2). Our experience is consistent with published data in the literature and illustrates the continued high complication rate seen during peripheral vascular interventions with the use of unfractionated heparin as a base anticoagulant. Evaluating Bivalirudin We have recently evaluated bivalirudin as an alternative to UHF during PTA. Bivalirudin, a direct thrombin inhibitor, was used in 48 consecutive PTA patients (excluding carotids). Bivalirudin was selected because of its predictable anticoagulation response and its ability to inhibit soluble and bound thrombin. Also, the safer profile of bivalirudin over heparin during percutaneous procedures has been demonstrated in several studies. In the Bivalirudin Angioplasty Trial (BAT),(9) bivalirudin reduced the risk of bleeding by 62% when compared to UFH (pThe Genesis Study In our study,(12) 48 consecutive patients (60.4% males, mean age 70.0 + 12.1) received bivalirudin as the primary anticoagulant during PTA (0.75 mg/kg bolus, 1.75 mg/kg/h during the procedure). Thirty-four (70.8%) had claudication and 6 (12.5%) had ulcerations. Thrombus was angiographically seen in 3 (6.3%) patients. In-hospital serious procedural complications were limited to 2 (4.2%) (exact 95% confidence interval: [0.5%,14.3%]) patients with major bleeding; none (0.0%) of the other following endpoints occurred: death, limb loss, emergent need for revascularization of the same vessel, embolic strokes, and vascular complications (exact 95% confidence intervals: [0.0%,6.1%]). This compared favorably to previously reported data using UFH and the same serious procedural complications endpoints from our group at the same institution (9.2%). Additional Data Others share our experience with bivalirudin in the periphery. 1. Grubbs and colleagues(13) reported their experience with 69 PTA patients receiving bivalirudin as a primary anticoagulant. In their series, there were no adverse events reported, including no major bleeding, acute thrombosis, or death. 2. Knopf et al.(14) also reported on 72 patients receiving bivalirudin during PTA. There were no deaths, major bleeding, strokes, or distal embolization in their series. 3. Furthermore, Allie et al.(15) have used bivalirudin in 180 renals and 75 iliac interventions with no major complications reported. A large multicenter study is needed to validate the above findings. The INFLAME Trial Recently, we have initiated a randomized trial (INFLAME) to study the vascular inflammatory response following PTA. A high baseline high-sensitivity-C Reactive Protein appears to correlate with an increased event rates following percutaneous coronary interventions. It is yet unclear whether inflammation following angioplasty in the periphery has serious clinical consequences. In INFLAME, the combination of a GP IIb/IIIa inhibitor with UFH is being studied for its ability to reduce acute inflammation following PTA. A secondary endpoint of the study is to evaluate in-hospital clinical events and at one-month follow-up. INFLAME is expected to be completed by the end of this year. The traditional use of UFH as a primary anticoagulant during peripheral vascular interventions is currently being challenged. Safer alternatives are being explored. Direct antithrombins (bivalirudin) or combination drugs (antithrombins and antiplatelets) during PTA might emerge as safer and more effective therapies than UFH.

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