24-carat gold, 14-carat gold, or platinum standards in the treatment of critical limb ischemia: bypass surgery or endovascular intervention?

Critical limb ischemia (CLI) remains a poorly understood, rarely reported, and inconsistently treated major global healthcare epidemic. The incidence in the US is estimated at 1% of the population aged 50 years and older and at approximately double that rate in the over-70 age group. These frequencies are expected to increase significantly with the aging population and the expected increase in diabetes. Within 1 year of being diagnosed with CLI, 40% to 50% of the now 20 million US diabetics will experience an amputation, and 20% to 25% will die. The estimate for treating CLI in the US alone is $10 to $20 billion per year, but just a 25% reduction in amputations could save $2.9 to $3.0 billion annually. Infrainguinal bypass surgery (IBS) utilizing autogenous saphenous vein has been considered the "24-carat gold standard" treatment for CLI, but over the last decade, endovascular therapy has emerged to seriously challenge IBS, which has created considerable controversy. Despite an overall lack of "hard" level I data, many interventionists are questioning the role of IBS as a first-line CLI therapy or are at least now considering IBS a "tainted" gold standard ("14-carat"). This review will examine the available evidence, but there should be no doubt regarding the huge global clinical and economic impact of CLI and amputations.

Creative limb-salvage surgical and endovascular revascularization strategies in treating critical limb ischemia.

Critical limb ischemia (CLI) is implicated in cases of between 220,000 to 240,000 amputations in the United States and Europe annually. Over the last five years, great technical strides have been made in both the surgical and nonsurgical endovascular treatments of CLI. This chapter analyzes and highlights those creative limb salvage strategies now used to treat CLI and save limbs.

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.

Patients with peripheral artery disease undergoing percutaneous peripheral interventions are at increased risk for complications without adequate anticoagulation.

Percutaneous peripheral interventions (PPI) are often complex procedures performed on high-risk patients with a significant thrombus burden. Although there is no approved anticoagulant for use in PPI, heparin is commonly used but is associated with several limitations. The APPROVE data provide a foundation for further study of bivalirudin in the setting of PPI.

The Angiomax Peripheral Procedure Registry of Vascular Events Trial (APPROVE): in-hospital and 30-day results.

BACKGROUND: High-risk patient characteristics and complexity of percutaneous peripheral intervention (PPI) procedures suggest a need for predictable and reliable anticoagulation. We undertook this study to assess the safety and efficacy of bivalirudin as the procedural anticoagulant in patients undergoing PPI of the renal, iliac, or femoral artery. METHODS: This was a prospective, open-label, single arm study inpatients undergoing PPI of the renal, iliac, or femoral vessels to assessbivalirudin as the sole procedural anticoagulant (0.75 mg/kg bolus/1.75 mg/kg/hr infusion). The primary endpoint was procedural success defined as residual stenosis < 20%. Secondary endpoints included ischemic events (death, myocardial infarction, unplanned revascularization, and amputation), and bleeding complications, as well as ACT values and times to sheath removal, ambulation, and discharge. RESULTS: 505 patients were enrolled at 26 sites. Procedural success was achieved in 95.0% of patients. Ischemic events were low (1.4%) and similar between vessel types. Protocol-defined major hemorrhage and TIMI major hemorrhage rates were 2.2% and 0.4%, respectively. Mean ACTs were similar among treatment groups (renal 353.8 seconds(s); iliac 335.9s, femoral, 343.5s). CONCLUSION: Bivalirudin provided consistent anticoagulation and similar outcomes in all vessel types treated at the dose tested. Ischemic and bleeding event rates were low, demonstrating the safe use of bivalirudin as a procedural anticoagulant in PPI.

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.

Clinical insights into the use of embolic protection devices during lower extremity peripheral vascular interventions.

The use of embolic protection devices (EPD) during lower extremity peripheral vascular interventions (PVI) remains controversial. We examine the current data and present our Louisiana experience with discussions regarding the unresolved issues surrounding the use of EPD during lower extremity PVI.

Safety and performance of targeted renal therapy: the Be-RITe! Registry.

PURPOSE: To evaluate the safety and patterns of use of targeted renal therapy (TRT) with the Benephit system. TRT, the delivery of therapeutic agents directly to the kidneys by renal arterial infusion, has the advantage of providing a higher local effective dose with potentially greater renal effects, while limiting systemic adverse effects due to renal first-pass elimination. METHODS: The Benephit System Renal Infusion Therapy (Be-RITe!) Multicenter Registry was a post-market registry following patients treated using the Benephit systems for TRT. The registry enrolled 501 patients (332 men; mean age 72.2+/-9.5 years) at high risk for contrast-induced nephropathy (CIN) during coronary or peripheral angiography/intervention or cardiovascular surgery. The Mehran score was used to compare the actual to predicted incidence of CIN within 48 hours post procedure. RESULTS: Bilateral renal artery cannulation was successful in 94.2%, with a mean cannulation time of 2.0 minutes. Either fenoldopam mesylate, sodium bicarbonate, alprostadil, or B-type natriuretic peptide (BNP) was infused for 184+/-212 minutes. Mean creatinine levels did not change significantly (baseline, 24, and 48 hours post procedure: 1.95, 1.99, and 1.98 mg/dL, respectively; p = NS). In 285 patients who received TRT with fenoldopam and were followed for at least 48 hours, the incidence of CIN was 71% lower than predicted (8.1% actual CIN versus 28.0% predicted; p<0.0001). Only 4 (1.4%) patients required dialysis (versus the 2.6% predicted rate, p = NS). CONCLUSION: The Benephit system and TRT during coronary and endovascular procedures in patients at high risk for renal failure is simple to use and safe. With the infusion of intrarenal fenoldopam, the incidence of CIN was significantly lower than predicted by risk score calculations.

Role of negative pressure wound therapy in treating peripheral vascular graft infections.

Wound complications involving large subcutaneous vessels can cause significant challenges for surgeons. Negative pressure wound therapy (NPWT) has been increasingly used for treating complex wounds in vascular surgery, including groin infections, either as a bridge to surgical closure or as a primary wound treatment modality. Although a growing body of evidence exists for managing various problematic wounds, such as diabetic foot ulcers and open abdominal wounds, the role of NPWT in wounds involving large blood vessels or wounds complicating infected vascular grafts has not been well defined. A multidisciplinary advisory panel reviewed the literature relevant to wounds related to vascular surgical procedures and complications, focusing on large subcutaneous or infected vascular conduits. The results supported by the literature and the clinical practice of the consensus panel suggested that NPWT can be a useful adjunct to the management of vascular groin infections and dehiscences but must be used with caution.

A review of the early experience with Targeted Renal Therapy for renal function preservation during endovascular and surgical treatments for cardiovascular disease.

Multiple reports describe the high clinical morbidity and mortality associated with contrast-induced nephropathy (CIN). Similarly, reports have described the glomerular filtration rate (GFR) and worsening renal function as predictors of adverse short and long-term outcomes in several large cardiovascular patient populations including acute myocardial infarction, congestive heart failure, coronary artery bypass surgery (CABG), and endovascular aneurysm repair (EVAR). Targeted renal therapy (TRT) is a novel emerging treatment where high-dose fenoldopam (FEN), a selective renal dopamine-1 receptor agonist and renal arteriolar vasodilator, is infused into both renal arteries via the US FDA-approved 5 Fr bifurcated Benephit PV Catheter Infusion System. TRT has been shown to significantly increase the GFR by 25% vs. placebo and IV-FEN (p < 0.001), which may have important clinical implications in CIN prophylaxis and during surgical procedures including CABG. The aim of this report is to review the early clinical experience and pilot trials with TRT in several clinical scenarios at high-risk for CIN or worsening renal function including percutaneous peripheral vascular interventions (PPI), percutaneous coronary interventions (PCI), CABG and EVAR.

Targeted renal therapy and contrast-induced nephropathy during endovascular abdominal aortic aneurysm repair: results of a feasibility pilot trial.

PURPOSE: To evaluate the feasibility of targeted renal therapy (TRT) to decrease the rate of contrast-induced nephropathy (CIN) during endovascular aortic aneurysm repair (EVAR) in patients at risk for CIN. METHODS: A prospective nonrandomized analysis of TRT was performed in 10 high-risk patients (8 men; median age 66.5 years, range 56-80) with pre-existing renal insufficiency. TRT involved high-dose intrarenal artery infusions of fenoldopam (FEN), a short acting selective dopamine-1 agonist and renal arteriolar vasodilator, delivered percutaneously via a left brachial access using the 5-F Benephit PV Infusion System during EVAR. RESULTS: There were no device-related complications. TRT infusion duration ranged from 3.5 to 6.0 hours (median 4.5). Median contrast dosage was 120 mL (range 50-200). At 24 and 72 hours after EVAR, creatinine clearance (CrCl) had improved in 7 (70%) patients, remained unchanged in 2 (20%), and declined >25% in 1 (10%); the latter returned to baseline on day 5. At 30 days, 7 (70%) patients had improved CrCl and 3 (30%) remained unchanged. CONCLUSION: TRT is feasible during EVAR in high-risk patients. Further investigation is warranted to determine the safety and efficacy of TRT in preserving renal function during EVAR.

Midterm outcomes from the TALON Registry: treating peripherals with SilverHawk: outcomes collection.

PURPOSE: To determine midterm clinical outcomes among patients with lower extremity peripheral arterial disease who underwent revascularization with catheter-based plaque excision (PE). METHODS: Between August 2003 and February 2005, 19 institutions participating in the observational, nonrandomized, multicenter TALON registry enrolled 601 consecutive patients (353 men; mean age 70+/-11, range 36-98) with 1258 symptomatic lower extremity atherosclerotic lesions (748 limbs) treated by plaque excision with the SilverHawk catheter. Approximately 50% of the patients had diabetes, and nearly one third of the procedures were indicated for Rutherford ischemia category > or =4. Mean lesion lengths above and below the knee, respectively, were 62.5+/-68.5 mm (interquartile range [IQR], 20.0-80.0) and 33.4+/-42.7 mm (IQR 15.0-37.5). The primary endpoints of the study were target lesion revascularization (TLR) at 6 and 12 months. RESULTS: The device achieved < or =50% residual diameter stenosis in 94.7% of lesions; procedural success was 97.6%. Nearly half (41.9%) of the procedures involved PE of > or =2 lesions. Nearly three quarters (73.3%) of the lesions did not require adjunctive therapy, and stent placement following PE occurred in only 6.3% of lesions. The 6- and 12-month rates of survival free of TLR were 90% and 80%, respectively. Rates of TLR were similar among patients with diabetes (11%) and without diabetes (9%). In the multivariate analysis, significant predictors of TLR at 6 months were a history of MI or coronary revascularization (HR 5.49, 95% CI 1.87 to 16.10, p=0.0008), multiple (> or =2) lesions (HR 1.37, 95% CI 1.11 to 1.70, p=0.0019), and increasing Rutherford category (HR 1.84, 95% CI 1.28 to 2.65, p=0.0003). Lesion length >50 mm was associated with a 2.9-fold increased risk for TLR (HR 2.88, 95% CI 1.18 to 7.01, p=0.012); lesion length >100 mm was associated with a 3.3-fold increase in TLR (HR 3.32, 95% CI 1.15 to 9.56, p=0.016). CONCLUSION: In patients undergoing revascularization for lower extremity atherosclerotic disease, catheter-based PE achieves favorable procedural success and avoids the need for repeat revascularization at midterm follow-up. These findings support PE as a primary endovascular therapy for patients undergoing lower extremity arterial revascularization.

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 treatment strategy for leg and sternal wound complications after coronary artery bypass graft surgery: bioengineered Apligraf.

PURPOSE: To demonstrate that bioengineered Apligraf improves time to wound healing in sternal and leg wound complications after coronary artery bypass surgery. DESCRIPTION: Between 1998 and 2001, 1,550 patients underwent coronary artery bypass surgery utilizing saphenous vein. In 45 (2.9%) of 1,550 patients, leg wound complications developed (group A); and in 15 (0.9%) of 1,550 patients, sternal wound complications developed (group B). Apligraf was utilized as the primary treatment for 30 (66%) of 45 leg wounds and for 9 (60%) of 15 sternal wounds. Traditional wound care included debridement and daily wet-to-dry dressings. EVALUATION: Time to wound healing ranged from 26 to 72 days (mean, 46) for Apligraf group A and from 34 to 120 days (mean, 84) for traditional wound care group A. The time to wound healing ranged from 21 to 80 days (mean, 39) for Apligraf group B, and from 36 to 110 days (mean, 62) for traditional care group B. Apligraf treatment was simpler, with less time and resource utilization than traditional wound care. CONCLUSIONS: Apligraf significantly improves time to wound healing in patients with leg and sternal wound complications and offers an attractive new treatment alternative to traditional wound care.

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.