Hans Krankenberg

Nitinol Stent Implantation Versus Percutaneous Transluminal Angioplasty in Superficial Femoral Artery Lesions up to 10 cm in Length: The Femoral Artery Stenting Trial (FAST)

Background— Endoluminal treatment of superficial femoral artery lesions is a matter of controversy. The present study was designed to investigate the impact of nitinol stenting of superficial femoral artery lesions with a maximum length of 10 cm on restenosis and clinical outcomes at 1 year. Methods and Results— Two hundred forty-four patients (168 men; 66±9 years) with a single superficial femoral artery lesion and chronic limb ischemia were randomized to implantation of a single Bard Luminexx 3 stent (123 patients) or stand-alone percutaneous transluminal angioplasty (PTA) (121 patients). Mean lesion length was 45 mm. Technical success (residual stenosis <50% for PTA, <30% for stenting) was achieved in 96 patients assigned to PTA (79%) and 117 patients assigned to stenting (95%); 13 PTA group patients (11%) “crossed over” to stenting. At 1 year, the primary end point of ultrasound-assessed binary restenosis was reached in 39 of 101 PTA group patients (38.6%) and 32 of 101 stent group patients (31.7%; absolute treatment difference, −6.9%; 95% CI, −19.7% to 6.2%; P=0.377). Target lesion revascularization rates at 1 year were 18.3% and 14.9%, respectively (absolute treatment difference, −3.3%; 95% CI, −13.0% to 6.4%; P=0.595). No statistically significant difference between treatment groups was observed at 12 months in the improvement by at least 1 Rutherford category of peripheral arterial disease. Conclusions— In the present study of patients with short superficial femoral artery lesions, the hypothesized absolute difference of 20% in binary restenosis at 1 year between the implantation of a single Luminexx nitinol stent and stand-alone PTA could not be demonstrated. A smaller difference requiring a larger trial might have been missed.

The LEVANT I (Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis) Trial for Femoropopliteal Revascularization : First-in-Human Randomized Trial of Low-Dose Drug-Coated Balloon Versus Uncoated Balloon Angioplasty

OBJECTIVES This study sought to evaluate the safety and efficacy of the Lutonix drug-coated balloon (DCB) coated with 2 μg/mm(2)paclitaxel and a polysorbate/sorbitol carrier for treatment of femoropopliteal lesions. BACKGROUND Percutaneous treatment of peripheral vascular disease is associated with a high recurrence. Paclitaxel-coated balloons at 3 μg/mm(2) formulated differently have shown promising results with reduced restenosis. Methods Subjects at 9 centers with Rutherford class 2 to 5 femoropopliteal lesions were randomized between June 2009 and December 2009 to treatment with Lutonix DCB (n = 49) versus uncoated balloons (control group [n = 52]), stratified by whether balloon-only treatment (n = 75) or stenting (n = 26) was intended. The primary endpoint was angiographic late lumen loss at 6 months. Secondary outcomes included adjudicated major adverse events (death, amputation, target lesion thrombosis, reintervention), functional outcomes, and pharmacokinetics. RESULTS Demographic, peripheral vascular disease, and lesion characteristics were matched, with mean lesion length of 8.1 3.8 cm and 42% total occlusions. At 6 months, late lumen loss was 58% lower for the Lutonix DCB group (0.46 1.13 mm) than for the control group (1.09 1.07 mm; p = 0.016). Composite 24-month major adverse events were 39% for the DCB group, including 15 target lesion revascularizations, 1 amputation, and 4 deaths versus 46% for uncoated balloon group, with 20 target lesion revascularizations, 1 thrombosis, and 5 deaths. Pharmacokinetics showed biexponential decay with peak concentration (Cmax) of 59 ng/ml and total observed exposure (AUC(all)) of 73 ng h/ml. For successful DCB deployment excluding 8 malfunctions, 6-month late lumen loss was 0.39 mm and the 24-month target lesion revascularization rate was 24%. CONCLUSIONS Treatment of femoropopliteal lesions with the low-dose Lutonix DCB reduced late lumen loss with safety comparable to that of control angioplasty. (LEVANT I, The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis; NCT00930813)

A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease: 1-year results from the ACHILLES trial.

OBJECTIVES The study investigated the efficacy and safety of a balloon expandable, sirolimus-eluting stent (SES) in patients with symptomatic infrapopliteal arterial disease. BACKGROUND Results of infrapopliteal interventions using balloon angioplasty and/or bare stents are limited by a relatively high restenosis rate, which could be potentially improved by stabilizing the lesion with a SES. METHODS Two hundred patients (total lesion length 27 ± 21 mm) were randomized to infrapopliteal SES stenting or percutaneous transluminal balloon angioplasty (PTA). The primary endpoint was 1-year in-segment binary restenosis by quantitative angiography. RESULTS Ninety-nine and 101 patients (mean age 73.4 years; 64% diabetics) were randomized to SES and PTA, respectively (8 crossover bailout cases to SES). At 1 year, there were lower angiographic restenosis rates (22.4% vs. 41.9%, p = 0.019), greater vessel patency (75.0% vs. 57.1%, p =0.025), and similar death, repeat revascularization, index-limb amputation rates, and proportions of patients with improved Rutherford class for SES versus PTA. CONCLUSIONS SES implantation may offer a promising therapeutic alternative to PTA for treatment of infrapopliteal peripheral arterial disease.

Sirolimus-eluting stents for treatment of infrapopliteal arteries reduce clinical event rate compared to bare-metal stents: long-term results from a randomized trial.

OBJECTIVES The study investigated the long-term clinical impact of sirolimus-eluting stents (SES) in comparison with bare-metal stents (BMS) in treatment of focal infrapopliteal lesions. BACKGROUND There is evidence that SES reduce the risk of restenosis after percutaneous infrapopliteal artery revascularization. No data from randomized trials are available concerning the clinical impact of this finding during long-term follow-up. METHODS The study extended the follow-up period of a prospective, randomized, multicenter, double-blind trial comparing polymer-free SES with placebo-coated BMS in the treatment of focal infrapopliteal de novo lesions. The main study endpoint was the event-free survival rate defined as freedom from target limb amputation, target vessel revascularization, myocardial infarction, and death. Secondary endpoints include amputation rates, target vessel revascularization, and changes in Rutherford-Becker class. RESULTS The trial included 161 patients. The mean target lesion length was 31 ± 9 mm. Thirty-five (23.3%) patients died during a mean follow-up period of 1,016 ± 132 days. The event-free survival rate was 65.8% in the SES group and 44.6% in the BMS group (log-rank p = 0.02). Amputation rates were 2.6% and 12.2% (p = 0.03), and target vessel revascularization rates were 9.2% and 20% (p = 0.06), respectively. The median (interquartile range) improvement in Rutherford-Becker class was -2 (-3 to -1) in the SES group and -1 (-2 to 0) in the BMS group, respectively (p = 0.006). CONCLUSIONS Long-term event-free survival, amputation rates, and changes in Rutherford-Becker class after treatment of focal infrapopliteal lesions are significantly improved with SES in comparison with BMS. (YUKON-Drug-Eluting Stent Below the Knee-Randomised Double-Blind Study [YUKON-BTX]; NCT00664963).

Intraarterial Administration of Bone Marrow Mononuclear Cells in Patients With Critical Limb IschemiaClinical Perspective

Background—Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking. Methods and Results—Forty patients with critical limb ischemia were included in a multicenter, phase II, double-blind, randomized-start trial to receive either intraarterial administration of BM-MNC or placebo followed by active treatment with BM-MNC (open label) after 3 months. Intraarterial administration of BM-MNC did not significantly increase ankle-brachial index and, thus, the trial missed its primary end point. However, cell therapy was associated with significantly improved ulcer healing (ulcer area, 3.2±4.7 cm2 to 1.89±3.5 cm2 [P=0.014] versus placebo, 2.92±3.5 cm2 to 2.89±4.1 cm2 [P=0.5]) and reduced rest pain (5.2±1.8 to 2.2±1.3 [P=0.009] versus placebo, 4.5±2.4 to 3.9±2.6 [P=0.3]) within 3 months. Limb salvage and amputation-free survival rates did not differ between the groups.Repeated BM-MNC administration and higher BM-MNC numbers and functionality were the only independent predictors of improved ulcer healing. Ulcer healing induced by repeated BM-MNC administration significantly correlated with limb salvage (r=0.8; P<0.001). Conclusions—Intraarterial administration of BM-MNC is safe and feasible and accelerates wound healing in patients without extensive gangrene and impending amputation. These exploratory findings of this pilot trial need to be confirmed in a larger randomized trial in patients with critical limb ischemia and stable ulcers. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00282646.

One-Year Outcome of Percutaneous Rotational Atherectomy with Aspiration in Infrainguinal Peripheral Arterial Occlusive Disease: The Multicenter Pathway PVD Trial

Purpose: To report a safety and efficacy study of a novel rotational atherectomy system with aspiration capabilities for the treatment of infrainguinal arterial lesions. Methods: From February 2006 to January 2007, 172 patients (88 women; mean age 72 years, range 51–93; 47% diabetics) with Rutherford class 1–5 lower limb ischemia were enrolled at 9 study sites. Inclusion criteria were atherosclerotic stenoses >70% and up to 10 cm long in the femoropopliteal segment or up to 3 cm long in the infrapopliteal vessels (reference vessel diameter 3.0–5.0 mm). In the study, 210 lesions (mean length 2.7 cm) were treated with the Pathway PV System, including total occlusions (31%), lesions with a moderate to high calcium score (51%), and post-angioplasty (non-stent) restenotic lesions (15%). The primary study endpoint was the 30-day major adverse event (MAE) rate. Results: Device success was 99% (208/210 lesions). MAE at 30 days was 1% (2 preplanned amputations). Clinically driven target lesion revascularization rates at 6 and 12 months were 15% (25/172) and 26% (42/162), respectively. The 1-year restenosis rate was 38.2% based on duplex imaging. The ankle-brachial index increased significantly from 0.59±0.21 at baseline to 0.82±0.27 (p<0.05) at 12 months. Mean Rutherford class improved from 3.0±0.9 at baseline to 1.5±1.3 at 1 year (p<0.05). Conclusion: The use of the Pathway PV System in atherosclerotic lesions appears to be safe and effective in improving stenosis severity, even in the presence of challenging lesion conditions. Vessel patency following intervention appears to be good up to 12 months, and these results translate into clinical benefit.

Two-year results after directional atherectomy of infrapopliteal arteries with the SilverHawk device.

Purpose: To report the 12- and 24-month results after directional atherectomy (DA) of below-the-knee (BTK) arterial lesions with the SilverHawk device. Methods: Forty-nine BTK lesions in 36 patients (58% men; mean age 70611 years) with peripheral occlusive disease of the lower limbs were treated with DA; 19 (53%) of the limbs were classified with Rutherford-Becker 4 or 5 ischemia. Target lesions were in the popliteal artery (n=6, 12%), tibioperoneal trunk (n=25, 51%), peroneal artery (n=10, 20%), anterior tibial artery (n=5, 10%), and posterior tibial artery (n=3, 6%). Nine (18%) lesions were located in a stent. Twelve lesions extended to 2 artery segments. The average degree of diameter stenosis was 89%±10% (range 70%–100%); there were 11 (22%) occlusions. The mean lesion length was 48±28 mm. Results: Sixteen (33%) lesions were treated after predilation; 33 (67%) lesions were treated with primary DA. All but 1 (2%) lesion could be treated with DA. In 19 (39%) lesions, additional balloon angioplasty was performed, and 2 (4%) lesions required stent implantation as a result of dissection. The mean stenosis diameter after DA was 12%±18% (range 0%–100%). After additional therapy, the mean stenosis diameter was 8%±9% (range 0%–100%). A residual stenosis ≤30% was achieved in 48 (98%) lesions. The mean ankle-brachial index significantly increased from 0.48±0.26 to 0.81±0.32 (p<0.05) before discharge and remained improved during follow-up. Primary and secondary patency rates were 67% and 91% after 1 year and 60% and 80% after 24 months. The 12-and 24-month cumulative event-free survival rates (primary patency) by Kaplan-Meier analysis were 58%±8% and 46%±9%; at the same time intervals, the cumulative survival rates (secondary patency) were 88%±6% and 73%±9%, respectively. Conclusion: BTK lesions can be treated successfully and safely with DA. Midterm clinical results are encouraging.

Midterm Results after Atherectomy-assisted Angioplasty of Below-Knee Arteries with Use of the Silverhawk Device

PURPOSE Prospective evaluation of the 3- and 6-month results after atherectomy of below-knee arterial lesions with a reference diameter of at least 2.0 mm with use of the Silverhawk device. MATERIALS AND METHODS Fifty-two below-knee lesions in 33 patients (61% men; mean age, 70 years +/- 11) with chronic peripheral occlusive disease of the lower limbs were treated with directional atherectomy. Target lesions were the popliteal artery (segment 3), n = 4 (8%); tibioperoneal trunk, n = 22 (42%); peroneal artery, n = 18 (34%); anterior tibial artery, n = 5 (10%); posterior tibial artery, n = 3 (6%); and in-stent lesions, n = 8 (16%). All interventions were performed via a 6-F sheath. The average degree of diameter stenosis was 89% +/- 10% (range, 70%-100%; n = 12 [23%] occlusions) and the mean lesion length was 48 mm +/- 28. RESULTS All but one lesion (2%) could be treated with the atherectomy catheter. After additional balloon angioplasty, all but one lesion was treated, with a residual stenosis no greater than 30% (98%), with 7.2 passes per lesion +/- 2.8 (range, 1-12) performed with the device. Fifteen lesions (29%) were treated after predilation and 37 (71%) were treated with primary atherectomy. In 15 lesions (29%), additional balloon angioplasty was performed, and two lesions required stent implantation as a result of dissection. The mean stenosis diameter after atherectomy was 12% +/- 18% (range, 0-100%). After additional therapy, the mean stenosis diameter was 6% +/- 9% (range, 0%-30%). A residual stenosis no greater than 30% was achieved in 50 lesions (96%). The mean ankle-brachial index significantly increased from 0.46 +/- 0.27 to 0.80 +/- 0.34 before discharge and remained improved during follow-up. One procedural complication (3%) was observed in which an intermittent occlusion of the target vessel occurred after an unsuccessful attempt to cross the lesion with the atherectomy device; this was then treated successfully with local lysis. One patient with one treated lesion died during follow-up. The rates of restenosis of at least 70% (diagnosed by duplex ultrasonography) were 14% (seven of 51 lesions) after 3 months and 22% (11 of 51) after 6 months. The 3-month and 6-month cumulative event-free survival were 91% +/- 4.1% and 76.9% +/- 5.8% and the 3-month and 6-month cumulative patency rates were 98% +/- 1.9% and 94.1% +/- 3.3%, respectively. CONCLUSION Below-knee native vessel lesions with a diameter of at least 2.0 mm can be treated with the Silverhawk catheter with a high success rate and a low complication rate. Midterm technical and clinical results are encouraging. Additional balloon angioplasty might be necessary in selected cases.

Percutaneous transluminal angioplasty of infrapopliteal arteries in patients with intermittent claudication: Acute and one‐year results

In advanced stages of infrapopliteal peripheral arterial occlusive disease with critical ischemia of the lower limb, the efficacy of percutaneous transluminal angioplasty (PTA) is well established. In contrast, PTA is currently not the therapy of choice in intermittent claudication (IC). In this prospective study, patients with IC were treated percutaneously. Technical aspects and long‐term results are presented. In 78 patients (61 males, or 78.2%; age, 71 ± 11 years) with IC (Rutherford grade 2 or 3), 104 interventions were performed. At baseline, the initial/absolute walking distance (IWD/AWD) was 49 ± 34/102 ± 88 m; the ankle‐brachial index (ABI) was 0.61 ± 0.2 before and 0.49 ± 0.2 after exercise. A crossover approach was used in 74% and an antegrade access in 26% of the cases. In 19 interventions (18.3%), the excimer laser technique was used, and in 26 interventions (25%) a total of 39 stents were implanted. Procedural success rate was 89.4%. IWD and AWD improved to 107 ± 67 m and 167 ± 74 m (P < 0.0001 vs. baseline each), respectively, and the ABI at rest and after exercise increased to 0.88 ± 0.13 and 0.72 ± 0.19 (P < 0.0001 vs. baseline each). Six complications occurred (5.8%). One embolic occlusion, two minor groin hematoma, one arteriovenous fistula, one compartment syndrome, and one perforation. All were treated conservatively. After 12 months, the primary patency rate was 66.3%, cumulative primary assisted patency rate was 81.9%, and secondary patency rate was 91.5%. Percutaneous revascularization of infrapopliteal arteries in patients with IC is feasible and associated with good acute clinical results and an encouraging long‐term patency rate. The complication rate is low. Catheter Cardiovasc Interv 2005;64:12–17.

Nitinol Stent Implantation in TASC A and B Superficial Femoral Artery Lesions: The Femoral Artery Conformexx Trial (FACT)

Purpose: To investigate the impact of nitinol stenting of superficial femoral artery (SFA) lesions with a maximum length of 10 cm (TASC-II A or B) on 1-year outcomes compared to a historical study cohort from the Femoral Artery Stent Trial (FAST). Methods: Between January 2004 and August 2005, 6 study sites enrolled 110 symptomatic patients (75 men; mean age 68±9 years) with a single de novo >70% SFA lesion <10 cm long treated with the self-expanding nitinol Conformexx stent. The primary study endpoint was binary restenosis determined by duplex ultrasound at 12 months. Secondary 12-month endpoints were target lesion revascularization (TLR), ankle-brachial index (ABI), mean Rutherford category, >1-class change in Rutherford category, and major adverse events. Data were analyzed according to the intention-to-treat principle and according to the actual treatment received (“on treatment” analysis). Outcomes were compared to the historical balloon angioplasty (BA) arm and the Luminexx 3 stent arm of the randomized FAST study. Results: Technical success was achieved in 106 (96%) patients; at 1 year, the primary endpoint of ultrasound-assessed binary restenosis was reached in 14 (23.3%) of 60 patients (95% CI 13.4% to 36%). This restenosis rate was lower versus the historical BA (38.6%, p=0.057) or Luminexx 3 stent controls (31.7%, p=0.284) from FAST. The clinically driven TLR was 7.4% (7 of 94 clinically controlled patients), which was also lower compared to 18.3% (p=0.098) and 14.9% (p=0.267) for the historical BA and Luminexx 3 stent groups, respectively. The mean Rutherford category was reduced from 2.75±0.79 to 0.94±1.38 (p<0.0001); 85.1% were improved by at least 1 Rutherford category. The ABI increased from 0.62±0.15 to 0.85±0.20 (p<0.0001). Conclusion: This study of patients with SFA lesions documented favorable outcomes using nitinol stents in TASC-II A or B lesions after 1 year. The study was underpowered to prove superiority of the Conformexx nitinol stent design compared to historical balloon only or Luminexx 3 stent groups.