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Use of DCBs in Long Femoropopliteal Lesions: Where Do We Stand?
Endovascular treatment has become the standard of care for most cases of symptomatic femoropopliteal peripheral artery disease.1,2 However, given the anatomic characteristics of the femoral artery, longer lesions are commonly harder to treat and have worse long-term outcomes. Decreased patency and increased need for revascularization in longer lesions have been demonstrated in plain balloon angioplasty, bare-metal stent, and atherectomy studies.3-7 Drug-eluting stents have demonstrated improvement over their bare-metal counterparts; in one single-center series, there was still a decline in patency but reasonably good freedom from repeat revascularization for very long lesions.8
Longer lesions also often possess other characteristics that challenge endovascular treatment, including calcium, in-stent restenosis (ISR), thrombus, and occlusions. Drug-coated balloons (DCBs) have been successfully used to treat lesions shorter than 10 cm, both in randomized controlled trials (RCTs) and larger single-arm registries.9-18 However, to date, there are only six studies (only one of which is an RCT) showing the results of DCB treatment of lesions longer than 20 cm (Table 1).19-24 Notably, these long lesions are often occlusive and calcified, and thus their treatment is associated with provisional stenting ranging from 10% to 50%. Despite the challenging nature of these lesions, outcomes appear to demonstrate the safety and effectiveness of DCB use in long lesions.
In response to these clinical results, the recent Society for Cardiovascular Angiography and Interventions (SCAI) guidelines recommended DCBs as the definitive therapy for SFA lesions longer than 20 cm, whether that lesion has calcium. ISR, or a chronic total occlusion.25 However, until recently, interventionalists have had to use up to four balloons to cover long and diffuse lesions. This incurs both a higher procedural cost to payers and patients, as well as an increase in procedure time. Shorter balloons also increase the chances of geographic miss, which was shown to negatively impact outcomes in the LEVANT I study.26 Importantly, care must be taken with long balloons to avoid oversizing in the distal segment.
Beyond cost, there are also other reasons to consider the use of long balloons. First, a relatively recent retrospective single-center analysis of 101 subjects demonstrated fewer type C–F dissections when using long percutaneous transluminal angioplasty (PTA) balloons.27 Although this study was performed with uncoated balloons, the mechanical principle remains similar, and reducing dissections in long femoropopliteal lesions could reduce the need for stenting and thus placement of a permanent metal implant. Second, if only one balloon is used as compared to two or three, an implanting physician may have time to allow slower balloon inflation and deflation times. The possible importance of this procedural characteristic was discussed as an explanation for the improved standard PTA outcomes in DCB trials by a panel at VIVA 2017 after presentation of the ILLUMINATE EU 2-year results, which had improved PTA outcomes compared to past studies.28
Luckily, longer balloons and expanded indications to treat longer lesions are coming onto the market in the United States, allowing interventionalists to more easily treat a broader set of lesions. In the United States, there are three balloons currently approved to treat femoropopliteal lesions: Stellarex™* DCB (Philips), Lutonix™* DCB (BD Interventional), and IN.PACT™ Admiral™ DCB (Medtronic). The Stellarex™* DCB is approved to treat lesions up to 180 mm, with balloon sizes up to 120 mm. The Lutonix™* DCB is approved to treat lesions up to 300 mm with balloon sizes up to 150 mm. In May 2018, the IN.PACT™ Admiral™ DCB received FDA approval to treat femoropopliteal lesions up to 360 mm in length, and as of June 2018, 200- and 250-mm balloons were approved for clinical use.
With these longer balloons available for clinical use, treatment options for peripheral artery disease have expanded. Interventionalists look forward to evaluating the long-term DCB results in patients with longer femoropopliteal lesions.
1. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg, 2007;45(suppl S):S5-67.
2. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2017;69:1465-1508.
3. Gray WA, Feiring A, Cioppi M, et al. S.M.A.R.T. self-expanding nitinol stent for the treatment of atherosclerotic lesions in the superficial femoral artery (STROLL): 1-year outcomes. J Vasc Interv Radiol. 2015;26:21-28.
4. Bosiers M, Deloose K, Callaert J, et al. Results of the Protege EverFlex 200-mm-long nitinol stent (ev3) in TASC C and D femoropopliteal lesions. J Vasc Surg. 2011;54:1042-1050.
5. Armstrong EJ, Saeed H, Alvandi B, et al. Nitinol self-expanding stents vs. balloon angioplasty for very long femoropopliteal lesions. J Endovasc Ther. 2014;21:34-43.
6. Rocha-Singh KJ, Jaff MR, Crabtree TR, et al; VIVA Physicians. Performance goals and endpoint assessments for clinical trials of femoropopliteal bare nitinol stents in patients with symptomatic peripheral arterial disease. Catheter Cardiovasc Interv. 2007;69:910-919.
7. Sixt S, Rastan A, Beschorner U, et al. Acute and long-term outcome of Silverhawk assisted atherectomy for femoro-popliteal lesions according the TASC II classification: a single-center experience. Vasa. 2010;39:229-236.
8. Phillips JA, Falls A, Kolluri R, et al. Full drug-eluting stent jacket: two-year results of a single-center experience with Zilver PTX stenting for long lesions in the femoropopliteal arteries. J Endovasc Ther. 2018;25:295-301.
9. Rosenfield K, Jaff MR, White CJ, et al. Trial of a paclitaxel-coated balloon for femoropopliteal artery disease. N Engl J Med. 2015;373:145-153.
10. Thieme M, Von Bilderling P, Paetzel C, et al. The 24-month results of the Lutonix global SFA registry: worldwide experience with Lutonix drug-coated balloon. JACC Cardiovasc Interv. 2017;10:1682-1690.
11. Krishnan P, Faries P, Niazi K, et al. Stellarex drug-coated balloon for treatment of femoropopliteal disease: twelve-month outcomes from the randomized ILLUMENATE pivotal and pharmacokinetic studies. Circulation. 2017;136:1102-1113.
12. Schroeder H, Werner M, Meyer DR, et al. Low-dose paclitaxel-coated versus uncoated percutaneous transluminal balloon angioplasty for femoropopliteal peripheral artery disease: one-year results of the ILLUMENATE European randomized clinical trial (randomized trial of a novel paclitaxel-coated percutaneous angioplasty balloon). Circulation. 2017;135:2227-2236.
13. Schroë H, Holden AH, Goueffic Y, et al. Stellarex drug-coated balloon for treatment of femoropopliteal arterial disease-the ILLUMENATE global study: 12-month results from a prospective, multicenter, single-arm study. Catheter Cardiovasc Interv. 2018;91:497-504.
14. Schneider PA, Laird JR, Tepe G, et al. Treatment effect of drug-coated balloons is durable to 3 years in the femoropopliteal arteries: long-term results of the IN.PACT SFA randomized trial. Circ Cardiovasc Interv. 2018;11:e005891.
15. Micari A, Brodmann M, Keirse K, et al; IN.PACT Global Study Investigators. Drug-coated balloon treatment of femoropopliteal lesions for patients with intermittent claudication and ischemic rest pain: 2-year results from the IN.PACT Global study. JACC Cardiovasc Interv. 2018;11:945-953.
16. Tepe G, Zeller T, Albrecht T, et al. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. 2008;358:689-699.
17. Werk M, Albrecht T, Meyer DR, et al. Paclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the randomized PACIFIER trial. Circ Cardiovasc Interv. 2012;5:831-840.
18. Scheinert D, Schulte KL, Zeller T, et al. Paclitaxel-releasing balloon in femoropopliteal lesions using a BTHC excipient: twelve-month results from the BIOLUX P-I randomized trial. J Endovasc Ther. 2015;22:14-21.
19. Lutonix 035 drug-coated balloon PTA catheter instructions for use. BAW1387400r3.
20. Micari A, Vadalà G, Castriota F, et al. 1-year results of paclitaxel-coated balloons for long femoropopliteal artery disease: evidence from the SFA-long study. JACC Cardiovasc Interv. 2016;9:950-956.
21. Scheinert D. Drug coated balloon treatment for patients with intermittent claudication: new insights from the IN.PACT Global study long lesion (≥15 cm) imaging cohort. Presented at: EuroPCR 2015; May 19–22, 2015; Paris, France.
22. Tepe G. IN.PACT Global drug-coated balloon for treatment of chronic total occlusions in the SFA. Presented at: Charing Cross 2016; April 26–29, 2016; London, United Kingdom.
23. Zeller T, Rastan A, Macharzina R, et al. Drug-coated balloons vs. drug-eluting stents for treatment of long femoropopliteal lesions. J Endovasc Ther. 2014;21:359-368.
24. Schmidt A, Piorkowski M, Görner H, et al. Drug-coated balloons for complex femoropopliteal lesions 2-year results of a real-world registry. JACC Cardiovasc Interv. 2016;9:715-724.
25. Feldman DN, Armstrong EJ, Aronow HD, et al. SCAI consensus guidelines for device selection in femoral-popliteal arterial interventions. Catheter Cardiovasc Interv. 2018;92:124-140.
26. Scheinert D, Duda S, Zeller T, et al. 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. JACC Cardiovasc Interv. 2014;7:10-19.
27. Tan M, Urasawa K, Koshida R, et al. Comparison of angiographic dissection patterns caused by long vs short balloons during balloon angioplasty of chronic femoropopliteal occlusions. J Endovasc Ther. 2018;25:192-200.
28. McKeown LA. Low-dose paclitaxel DCB shows long-term durability in treating PAD. TCTMD/The Hear Beat. September 18, 2017. https://www.tctmd.com/news/low-dose-paclitaxel-dcb-shows-long-term-durability-treating-pad. Accessed September 5, 2018.
Gary M. Ansel, MD
System Medical Chief, Vascular Services
Associate Medical Director
OhioHealth Research Institute
Assistant Clinical Professor of Medicine
Department of Medicine
University of Toledo Medical Center
Disclosures: Advisor for Abbott Vascular, Boston Scientific Corporation, Medtronic, Philips & Volcano Philips, Gore & Associates, and Surmodics; a compensated board member of VIVA Physicians, a 501(c)(3) not-for-profit education and research organization; equity investor in Primacea; receives royalties from Cook Medical.
IN.PACT™ Admiral™ Brief Statement
Indications for Use:
- The IN.PACT™ Admiral™ Paclitaxel-Coated PTA Balloon catheter is indicated for percutaneous transluminal angioplasty, after appropriate vessel preparation, of de novo, restenotic, or in-stent restenotic lesions with lengths up to 360 mm in superficial femoral or popliteal arteries with reference vessel diameters of 4-7 mm.
- The IN.PACT™ Admiral™ DCB is contraindicated for use in:
- Coronary arteries, renal arteries, and supra-aortic/cerebrovascular arteries
- Patients who cannot receive recommended antiplatelet and/or anticoagulant therapy
- Patients judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the delivery system
- Patients with known allergies or sensitivities to paclitaxel
- Women who are breastfeeding, pregnant or are intending to become pregnant or men intending to father children. It is unknown whether paclitaxel will be excreted in human milk and whether there is a potential for adverse reaction in nursing infants from paclitaxel exposure.
- Use the product prior to the Use-by Date specified on the package.
- Contents are supplied sterile. Do not use the product if the inner packaging is damaged or opened.
- Do not use air or any gaseous medium to inflate the balloon. Use only the recommended inflation medium (equal parts contrast medium and saline solution).
- Do not move the guidewire during inflation of the IN.PACT™ Admiral™ DCB.
- Do not exceed the rated burst pressure (RBP). The RBP is 14 atm (1419 kPa) for all balloons except the 200 and 250 mm balloons. For the 200 and 250 mm balloons the RBP is 11 atm (1115 kPa). The RBP is based on the results of in vitro testing. Use of pressures higher than RBP may result in a ruptured balloon with possible intimal damage and dissection.
- The safety and effectiveness of using multiple IN.PACT™ Admiral™ DCBs with a total drug dosage exceeding 34,854 µg of paclitaxel in a patient has not been clinically evaluated.
- This product should only be used by physicians trained in percutaneous transluminal angioplasty (PTA).
- This product is designed for single patient use only. Do not reuse, reprocess, or resterilize this product. Reuse, reprocessing, or resterilization may compromise the structural integrity of the device and/or create a risk of contamination of the device, which could result in patient injury, illness, or death.
- Assess risks and benefits before treating patients with a history of severe reaction to contrast agents.
- The safety and effectiveness of the IN.PACT™ Admiral™ DCB used in conjunction with other drug-eluting stents or drug-coated balloons in the same procedure or following treatment failure has not been evaluated.
- The extent of the patient's exposure to the drug coating is directly related to the number of balloons used. Refer to the Instructions for Use (IFU) for details regarding the use of multiple balloons and paclitaxel content.
- The use of this product carries the risks associated with percutaneous transluminal angioplasty, including thrombosis, vascular complications, and/or bleeding events
- Vessel preparation using only pre-dilatation was studied in the clinical study. Other methods of vessel preparation, such as atherectomy, have not been studied clinically with IN.PACT™ Admiral™ DCB.
- This product is not intended for the expansion or delivery of a stent
Potential Adverse Effects
- The potential adverse effects (e.g. complications) associated with the use of the device are: abrupt vessel closure; access site pain; allergic reaction to contrast medium, antiplatelet therapy, or catheter system components (materials, drugs, and excipients); amputation/loss of limb; arrhythmias; arterial aneurysm; arterial thrombosis; arteriovenous (AV) fistula; death; dissection; embolization; fever; hematoma; hemorrhage; hypotension/hypertension; inflammation; ischemia or infarction of tissue/organ; local infection at access site; local or distal embolic events; perforation or rupture of the artery; pseudoaneurysm; renal insufficiency or failure; restenosis of the dilated artery; sepsis or systemic infection; shock; stroke; systemic embolization; vessel spasms or recoil; vessel trauma which requires surgical repair.
- Potential complications of peripheral balloon catheterization include but are not limited to the following: balloon rupture; detachment of a component of the balloon and/or catheter system; failure of the balloon to perform as intended; failure to cross the lesion.
- Although systemic effects are not anticipated, potential adverse events that may be unique to the paclitaxel drug coating include but are not limited to: allergic/immunologic reaction; alopecia; anemia; gastrointestinal symptoms; hematologic dyscrasia (including leucopenia, neutropenia, thrombocytopenia); hepatic enzyme changes; histologic changes in vessel wall, including inflammation, cellular damage, or necrosis; myalgia/arthralgia; myelosuppression; peripheral neuropathy.
- Refer to the Physician's Desk Reference for more information on the potential adverse effects observed with paclitaxel. There may be other potential adverse effects that are unforeseen at this time.
- Please reference appropriate product Instructions for Use for a detailed list of indications, warnings, precautions and potential adverse effects. This content is available electronically at www.manuals.medtronic.com.
- Federal law (USA) restricts this device to sale by or on the order of a physician.
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