Richard R. Saxon

Paclitaxel-Eluting Stents Show Superiority to Balloon Angioplasty and Bare Metal Stents in Femoropopliteal Disease Twelve-Month Zilver PTX Randomized Study Results

Background— Sustained benefits of drug-eluting stents in femoropopliteal arteries have not been demonstrated. This prospective, multinational, randomized study was designed to compare the 12-month safety and effectiveness of a polymer-free, paclitaxel-coated nitinol drug-eluting stent (DES) with percutaneous transluminal angioplasty (PTA) and provisional bare metal stent (BMS) placement in patients with femoropopliteal peripheral artery disease. Methods and Results— Patients were randomly assigned to primary DES implantation (n=236) or PTA (n=238). Demographics and lesion characteristics were similar between groups (eg, average lesion length, approximately 65±40 mm). One hundred twenty patients had acute PTA failure and underwent secondary random assignment to provisional DES (n=61) or BMS (n=59). Primary end points were the 12-month rates of event-free survival and patency in the primary DES and PTA groups. Compared with the PTA group, the primary DES group exhibited superior 12-month event-free survival (90.4% versus 82.6%; P=0.004) and primary patency (83.1% versus 32.8%; P<0.001), satisfying the primary hypotheses. In the secondary evaluations, (1) the primary DES group exhibited superior clinical benefit compared with the PTA group (88.3% versus 75.8%; P<0.001), (2) the provisional DES group exhibited superior primary patency (89.9% versus 73.0%; P=0.01) and superior clinical benefit (90.5% and 72.3%, P=0.009) compared with the provisional BMS group, and (3) the stent fracture rate (both DES and BMS) was 0.9% (4/457). Conclusions— Femoropopliteal peripheral artery disease treatment with the paclitaxel-eluting stent was associated with superior 12-month outcomes compared with PTA and provisional BMS placement. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00120406.

Randomized, Multicenter Study Comparing Expanded Polytetrafluoroethylene–covered Endoprosthesis Placement with Percutaneous Transluminal Angioplasty in the Treatment of Superficial Femoral Artery Occlusive Disease

PURPOSE To compare the safety and effectiveness of the Viabahn endoprosthesis with that of percutaneous transluminal angioplasty (PTA) alone in the treatment of symptomatic peripheral arterial disease (PAD) affecting the superficial femoral artery (SFA). MATERIALS AND METHODS From 1998 to 1999, patients with symptomatic SFA PAD were enrolled in a prospective, multicenter randomized study and underwent either PTA alone (n = 100) or PTA followed by stent-graft placement (expanded polytetrafluoroethylene/nitinol self-expanding stent-graft) (n = 97) for stenoses or occlusions of the SFA that were 13 cm long or shorter. At baseline, there were no significant differences between the PTA and stent-graft treatment groups, including chronic limb ischemia status and treated lesion length. RESULTS The stent-graft group had a significantly higher technical success rate (95% vs 66%, P < .0001) and 1-year primary vessel patency rate at duplex ultrasonography (65% vs 40%, P = .0003). A patency benefit was seen for lesions at least 3 cm long. At 12 months, chronic limb ischemia status was 15% further improved for the stent-graft group (P = .003). There were no significant differences between treatment groups with regard to the occurrence of early or late major adverse events. CONCLUSIONS In this multicenter study, the patency, technical success, and clinical status results obtained with stent-grafts were superior to those obtained with PTA alone.

Durable Clinical Effectiveness With Paclitaxel-Eluting Stents in the Femoropopliteal Artery: 5-Year Results of the Zilver PTX Randomized Trial

Background— This randomized controlled trial evaluated clinical durability of Zilver PTX, a paclitaxel-coated drug-eluting stent (DES), for femoropopliteal artery lesions. Outcomes compare primary DES versus percutaneous transluminal angioplasty (PTA), overall DES (primary and provisional) versus standard care (PTA and provisional Zilver bare metal stent [BMS]), and provisional DES versus provisional BMS. Methods and Results— Patients with symptomatic femoropopliteal artery disease were randomly assigned to DES (n=236) or PTA (n=238). Approximately 91% had claudication; 9% had critical limb ischemia. Patients experiencing acute PTA failure underwent secondary randomization to provisional BMS (n=59) or DES (n=61). The 1-year primary end points of event-free survival and patency showed superiority of primary DES in comparison with PTA; these results were sustained through 5 years. Clinical benefit (freedom from persistent or worsening symptoms of ischemia; 79.8% versus 59.3%, P<0.01), patency (66.4% versus 43.4%, P<0.01), and freedom from reintervention (target lesion revascularization, 83.1% versus 67.6%, P<0.01) for the overall DES group were superior to standard care in nonrandomized comparisons. Similarly, clinical benefit (81.8% versus 63.8%, P=0.02), patency (72.4% versus 53.0%, P=0.03), and freedom from target lesion revascularization (84.9% versus 71.6%, P=0.06) with provisional DES were improved over provisional BMS. These results represent >40% relative risk reduction for restenosis and target lesion revascularization through 5 years for the overall DES in comparison with standard care and for provisional DES in comparison with provisional BMS. Conclusions— The 5-year results from this large study provide long-term information previously unavailable regarding endovascular treatment of femoropopliteal artery disease. The Zilver PTX DES provided sustained safety and clinical durability in comparison with standard endovascular treatments. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00120406.

Stent-Grafts for De Novo TIPS: Technique and Early Results

PURPOSE To evaluate the potential benefits of placing a polytetrafluoroethylene (PTFE)-covered stent-graft during initial creation of a transjugular intrahepatic portosystemic shunt (TIPS) in clinical practice. MATERIALS AND METHODS De novo TIPS were created with a PTFE stent-graft in four male and four female patients with symptomatic portal hypertension awaiting liver transplant. Their ages ranged from 35 to 62 (mean, 47) years. Patients were followed with TIPS ultrasound (US) and/or venography until liver transplantation or death; one remains under active study. Six recovered specimens underwent gross and microscopic evaluation. RESULTS All TIPS placements were successful. Six shunts were primarily patent, with a mean patency of 289 days, through completion of the study. Five were found to be patent at transplant and one was found to be patent at autopsy. Explant evaluation revealed a smooth, thin layer of neointima and exclusion of biliary secretions. Three patients developed a total of four stenoses (one tandem lesion) during follow-up, leading to revision in two patients. Mean primary and total patency in these patients was achieved after 279 and 463 days, respectively. A previously occult moderate stenosis was detected after explant in another patient. Only one (nonsignificant) stenosis clearly developed in an area covered by PTFE. CONCLUSION Placement of a de novo PTFE stent-graft during TIPS creation is feasible and may extend primary shunt patency. Appropriate positioning of the stent-graft is critical.

A New Era for Transjugular Intrahepatic Portosystemic Shunts

CIRRHOSIS affects approximately 300,000 adults in North America and causes more than 32,000 deaths annually (1). Most of the morbidity associated with cirrhosis results from the development of portal hypertension and its principal sequelae: variceal hemorrhage and ascites. Creation of a transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive means of creating a portosystemic shunt that can markedly decrease portal hypertension and its complications. Like so many other great advances in medicine, TIPS was first conceived by serendipity. In 1969, Rosch and colleagues were attempting to perform transjugular cholangiography in animals by puncturing across the substance of the liver from the hepatic vein. They often entered the portal vein and quickly realized that they had discovered a new technique for creating an “intrahepatic” portosystemic shunt (2). Rosch and others subsequently went on to develop the TIPS procedure. In the early 1990s, large clinical trials proved the clinical utility of the TIPS procedure as a bridge to transplantation in patients with severe complications of portal hypertension (3–5). Since that time, a number of randomized trials that compared TIPS creation to a course of endoscopic therapy for the prevention of recurrent variceal bleeding have been completed (6–12). All these studies have shown essentially the same thing: that recurrent variceal bleeding is significantly less frequent after TIPS creation (in 10%–25% of patients) than after endoscopic therapy (in 35%–50%). However, TIPS creation is also associated with a higher rate of hepatic encephalopathy (approximately 30%, compared with 15% with endoscopic therapy). A significant difference in long-term survival has not been demonstrated. Because of these results, gastroenterologists and hepatologists generally consider TIPS creation a second-line therapy that is most useful as a bridge to transplantation. Moreover, the clinical utility of TIPS creation has always been limited by problems with recurrent stenosis and occlusion. Surveillance and multiple repeated interventions are required to maintain patency in more than 50% of patients within 1 year. This leads to added expense and increased clinical failure. In patients with high function and Child class A disease, selective surgical shunts are often preferable because of their durability and perceived lower associated encephalopathy rates. The role of TIPS relative to other available therapies is dramatically limited by poor patency, the cost of surveillance and repeat intervention, and concerns about hepatic encephalopathy. In 1995, our group began to explore the use of handmade stent-grafts for the creation of TIPS and demonstrated a marked improvement in patency relative to uncovered shunts, but only when expanded polytetrafluoroethylene (ePTFE) was used as the covering material (13). We went on to report the first small series of patients in 1997, in which a marked improvement in patency and clinical outcome was demonstrated (14); these results were later reproduced and confirmed by Haskal and associates (15,16). It is interesting to note how little interest there has been on the part of device manufacturers in the design and development of a device dedicated to TIPS since those initial reports. Unlike with endografts for aneurysms and stents of all types for other applications, it has taken a long time for a commercial stent-graft to be developed and tested for the TIPS application. It is a lesson in medical economics when one realizes that only one company (W.L. Gore & Associates, Flagstaff, AZ) has pursued development of a dedicated device. A relatively small, underinsured patient population does not attract great attention from large device manufacturers no matter how beneficial the advance might be medically. In this issue of the Journal of Vascular and Interventional Radiology, the study by Hausegger et al (17) adds substantially to a growing body of knowledge about the creation of TIPS with use of a commercial ePTFE-covered stent-graft that is designed for TIPS creation and revision. The question arises as to whether the results are substantially different than those with uncovered stents, and, if so, whether that will change the role of TIPS in the From the San Diego Vascular Institute, Diagnostic Imaging and Interventional Radiology, North County Radiology Medical Group, Tri-City Medical Center, 4002 Vista Way, Oceanside, California 92056. Received December 3, 2003; revision requested December 8; revision received and accepted December 11. Address correspondence to R.R.S.; E-mail: rsaxon5@cox.net

Durable Clinical Effectiveness With Paclitaxel-Eluting Stents in the Femoropopliteal ArteryCLINICAL PERSPECTIVE: 5-Year Results of the Zilver PTX Randomized Trial

Background— This randomized controlled trial evaluated clinical durability of Zilver PTX, a paclitaxel-coated drug-eluting stent (DES), for femoropopliteal artery lesions. Outcomes compare primary DES versus percutaneous transluminal angioplasty (PTA), overall DES (primary and provisional) versus standard care (PTA and provisional Zilver bare metal stent [BMS]), and provisional DES versus provisional BMS. Methods and Results— Patients with symptomatic femoropopliteal artery disease were randomly assigned to DES (n=236) or PTA (n=238). Approximately 91% had claudication; 9% had critical limb ischemia. Patients experiencing acute PTA failure underwent secondary randomization to provisional BMS (n=59) or DES (n=61). The 1-year primary end points of event-free survival and patency showed superiority of primary DES in comparison with PTA; these results were sustained through 5 years. Clinical benefit (freedom from persistent or worsening symptoms of ischemia; 79.8% versus 59.3%, P<0.01), patency (66.4% versus 43.4%, P<0.01), and freedom from reintervention (target lesion revascularization, 83.1% versus 67.6%, P<0.01) for the overall DES group were superior to standard care in nonrandomized comparisons. Similarly, clinical benefit (81.8% versus 63.8%, P=0.02), patency (72.4% versus 53.0%, P=0.03), and freedom from target lesion revascularization (84.9% versus 71.6%, P=0.06) with provisional DES were improved over provisional BMS. These results represent >40% relative risk reduction for restenosis and target lesion revascularization through 5 years for the overall DES in comparison with standard care and for provisional DES in comparison with provisional BMS. Conclusions— The 5-year results from this large study provide long-term information previously unavailable regarding endovascular treatment of femoropopliteal artery disease. The Zilver PTX DES provided sustained safety and clinical durability in comparison with standard endovascular treatments. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00120406.

Durable Clinical Effectiveness With Paclitaxel-Eluting Stents in the Femoropopliteal ArteryCLINICAL PERSPECTIVE

Background— This randomized controlled trial evaluated clinical durability of Zilver PTX, a paclitaxel-coated drug-eluting stent (DES), for femoropopliteal artery lesions. Outcomes compare primary DES versus percutaneous transluminal angioplasty (PTA), overall DES (primary and provisional) versus standard care (PTA and provisional Zilver bare metal stent [BMS]), and provisional DES versus provisional BMS. Methods and Results— Patients with symptomatic femoropopliteal artery disease were randomly assigned to DES (n=236) or PTA (n=238). Approximately 91% had claudication; 9% had critical limb ischemia. Patients experiencing acute PTA failure underwent secondary randomization to provisional BMS (n=59) or DES (n=61). The 1-year primary end points of event-free survival and patency showed superiority of primary DES in comparison with PTA; these results were sustained through 5 years. Clinical benefit (freedom from persistent or worsening symptoms of ischemia; 79.8% versus 59.3%, P<0.01), patency (66.4% versus 43.4%, P<0.01), and freedom from reintervention (target lesion revascularization, 83.1% versus 67.6%, P<0.01) for the overall DES group were superior to standard care in nonrandomized comparisons. Similarly, clinical benefit (81.8% versus 63.8%, P=0.02), patency (72.4% versus 53.0%, P=0.03), and freedom from target lesion revascularization (84.9% versus 71.6%, P=0.06) with provisional DES were improved over provisional BMS. These results represent >40% relative risk reduction for restenosis and target lesion revascularization through 5 years for the overall DES in comparison with standard care and for provisional DES in comparison with provisional BMS. Conclusions— The 5-year results from this large study provide long-term information previously unavailable regarding endovascular treatment of femoropopliteal artery disease. The Zilver PTX DES provided sustained safety and clinical durability in comparison with standard endovascular treatments. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00120406.