Systematic Review and Meta-analysis of Randomized Controlled Trials of Paclitaxel-Coated Balloon Angioplasty in the Femoropopliteal Arteries

Abstract

Purpose: To provide a qualitative analysis and quantitative synthesis of randomized controlled trials (RCTs) investigating paclitaxel-coated balloons (PCBs) in the femoropopliteal artery. Methods: PubMed, EMBASE, AMED, Scopus, CENTRAL, online content, and abstracts from international meetings were last screened in April 2015 for eligible RCTs using the PRISMA selection process. Risk of bias was assessed using the Cochrane Collaboration’s tool, and quality of evidence was evaluated with the GRADE system. Outcome measures included late lumen loss (LLL) at 6 months and event rates of major limb amputations, binary lesion restenosis, and target lesion revascularization (TLR). Pooled treatment effects were analyzed in a random effects model to account for clinical heterogeneity; the outcomes are presented as the rate ratios (RRs) and their 95% confidence intervals (CIs). Extensive meta-regression was performed to analyze potential confounders. The review was registered in the PROSPERO database (CRD42015023938; www.crd.york.ac.uk/PROSPERO ). Results: Eleven RCTs with 1609 subjects (1403 claudicants and 206 patients with critical limb ischemia) with medium-length femoropopliteal lesions (mean range 5.1–11.9 cm) were included. There was consistently high-quality evidence supporting the clear superiority of PCBs in terms of reduced LLL (mean difference −0.89 mm, 95% CI −1.14 to −0.64, p<0.001), less binary restenosis (RR 0.47, 95% CI 0.37 to 0.61, p<0.001), and fewer TLR events (RR 0.33, 95% CI 0.22 to 0.49, p<0.001). Major amputations were rare in both active and control arms (pooled event rate: 0.7%, 95% CI 0.3% to 1.2%). Results were stable across all potential risk modifiers and in the presence of stents as well. There was high-quality evidence that the dose of paclitaxel was related to the magnitude of the treatment effect; standard dose (3.0-μg and 3.5-μg) PCBs were significantly more effective compared with low-dose 2-μg PCB in reducing both restenosis (RR 2.1, 95% CI 1.2 to 3.4, p<0.001) and TLR (RR 2.5, 95% CI 1.9 to 3.8, p<0.001). Conclusion: PCBs reduce by more than half the rates of restenosis and TLR in the femoropopliteal artery regardless of stent placement. Biologic effect size may vary according to paclitaxel bioavailability.

Keywords

amputation balloon angioplasty bioavailability dose femoropopliteal segment meta-analysis meta-regression paclitaxel restenosis stent target lesion revascularization

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References

Rooke

Hirsch

Misra

Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2013;61:1555–1570.

Diamantopoulos

Katsanos

. Treating femoropopliteal disease: established and emerging technologies. Semin Intervent Radiol. 2014;31:345–352.

Kasapis

Henke

Chetcuti

Routine stent implantation vs. Percutaneous transluminal angioplasty in femoropopliteal artery disease: a meta-analysis of randomized controlled trials. Eur Heart J. 2009;30:44–55.

Dippel

Makam

Kovach

Randomized controlled study of excimer laser atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from the EXCITE ISR trial (excimer laser randomized controlled study for treatment of femoropopliteal in-stent restenosis). JACC Cardiovasc Interv. 2015;8:92–101.

Spiliopoulos

Katsanos

Karnabatidis

Cryoplasty versus conventional balloon angioplasty of the femoropopliteal artery in diabetic patients: long-term results from a prospective randomized single-center controlled trial. Cardiovasc Intervent Radiol. 2010;33:929–938.

Katsanos

Tepe

Tsetis

Standards of practice for superficial femoral and popliteal artery angioplasty and stenting. Cardiovasc Intervent Radiol. 2014;37:592–603.

Diamantopoulos

Katsanos

. Atherectomy of the femoropopliteal artery: a systematic review and meta-analysis of randomized controlled trials. J Cardiovasc Surg (Torino). 2014;55:655–665.

Katsanos

Spiliopoulos

Karunanithy

Bayesian network meta-analysis of nitinol stents, covered stents, drug-eluting stents, and drug-coated balloons in the femoropopliteal artery. J Vasc Surg. 2014;59:1123–1133.e8.

Dake

Ansel

Jaff

Sustained safety and effectiveness of paclitaxel-eluting stents for femoropopliteal lesions: 2-year follow-up from the ZILVER PTX randomized and single-arm clinical studies. J Am Coll Cardiol. 2013;61:2417–2427.

10.

Neil

. Stent fracture in the superficial femoral and proximal popliteal arteries: literature summary and economic impacts. Perspect Vasc Surg Endovasc Ther. 2013;25:20–27.

11.

Haude

Erbel

Erne

Safety and performance of the drug-eluting absorbable metal scaffold (DREAMS) in patients with de-novo coronary lesions: 12 month results of the prospective, multicentre, first-in-man BIOSOLVE-I trial. Lancet. 2013;381:836–844.

12.

Siablis

Kitrou

Spiliopoulos

Paclitaxel-coated balloon angioplasty versus drug-eluting stenting for the treatment of infrapopliteal long-segment arterial occlusive disease: the ideas randomized controlled trial. JACC Cardiovasc Interv. 2014;7:1048–1056.

13.

Higgins

Altman

Gotzsche

The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

14.

Guyatt

Oxman

Vist

GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–926.

15.

Moher

Liberati

Tetzlaff

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.

16.

Sacks

Marinelli

Martin

Reporting standards for clinical evaluation of new peripheral arterial revascularization devices. J Vasc Interv Radiol. 2003;14(9 pt 2):S395–S404.

17.

Tepe

. Cotavance paclitaxel-coated balloon vs. uncoated balloon angioplasty for treatment of in-stent restenosis in SFA and the popliteal arteries: the COPA CABANA trial. Paper presented at: LINC 2015; January 27–30, 2015; Lepzig, Germany. http://www.leipzig-interventional-course.com . Accessed February 2015.

18.

Tepe

Zeller

Albrecht

Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. 2008;358:689–699.

19.

Werk

Langner

Reinkensmeier

Inhibition of restenosis in femoropopliteal arteries: paclitaxel-coated versus uncoated balloon. Femoral paclitaxel randomized pilot trial. Circulation. 2008;118:1358–1365.

20.

Fanelli

Cannavale

Boatta

Lower limb multilevel treatment with drug-eluting balloons: 6-month results from the DEBELLUM randomized trial. J Endovasc Ther. 2012;19:571–580.

21.

Fanelli

Cannavale

Corona

The “DEBELLUM”–lower limb multilevel treatment with drug eluting balloon–randomized trial: 1-year results. J Cardiovasc Surg (Torino). 2014;55:207–216.

22.

Krankenberg

. FAIR: drug-eluting balloon vs. PTA for superficial femoral artery in-stent restenosis 12-month results. Paper presented at: LINC 2014; January 28–31, 2014; Lepzig, Germany. http://www.leipzig-interventional-course.com . Accessed February 2015.

23.

Liistro

Grotti

Porto

Drug-eluting balloon in peripheral intervention for the superficial femoral artery: the DEBATE-SFA randomized trial (drug eluting balloon in peripheral intervention for the superficial femoral artery). JACC Cardiovasc Interv. 2013;6:1295–1302.

24.

Tepe

Laird

Schneider

Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the In.Pact SFA randomized trial. Circulation. 2015;131:495–502.

25.

Werk

Albrecht

Meyer

Paclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the randomized PACIFIER trial. Circ Cardiovasc Interv. 2012;5:831–840.

26.

Scheinert

Schulte

Zeller

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.

27.

Scheinert

Duda

Zeller

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.

28.

FDA, Review P130024. Lutonix® drug coated balloon PTA catheter for treatment of stenotic or obstructive lesions in the femoropopliteal artery. 2014. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cftopic/pma/pma.cfm?num=p130024 . Accessed February 2015.

29.

Rosenfield

Jaff

White

Trial of a paclitaxel-coated balloon for femoropopliteal artery disease. N Engl J Med. 2015;373:145–153.

30.

Higgins

Thompson

Deeks

Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560.

31.

Begg

. Publication bias. In: Cooper

Hedges

, eds. The Handbook of Research Synthesis. 1994:399–409.

32.

Krokidis

Spiliopoulos

Katsanos

Peripheral applications of drug-coated balloons: past, present and future. Cardiovasc Intervent Radiol. 2013;36:281–291.

33.

Zeller

Baumgartner

Scheinert

Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the In.Pact deep randomized trial. J Am Coll Cardiol. 2014;64:1568–1576.

34.

Cassar

Bachoo

Ford

Markers of coagulation activation, endothelial stimulation and inflammation in patients with peripheral arterial disease. Eur J Vasc Endovasc Surg. 2005;29:171–176.

35.

Siablis

Karnabatidis

Katsanos

Infrapopliteal application of paclitaxel-eluting stents for critical limb ischemia: midterm angiographic and clinical results. J Vasc Interv Radiol. 2007;18:1351–1361.

36.

Scheller

Speck

Abramjuk

Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Circulation. 2004;110:810–814.

37.

Posa

Nyolczas

Hemetsberger

Optimization of drug-eluting balloon use for safety and efficacy: evaluation of the 2nd generation paclitaxel-eluting Dior balloon in porcine coronary arteries. Catheter Cardiovasc Interv. 2010;76:395–403.

38.

Mena

Pietras

Local delivery of paclitaxel in the treatment of peripheral arterial disease. Eur J Clin Invest. 2015;45:333–345.

39.

Cremers

Biedermann

Mahnkopf

Comparison of two different paclitaxel-coated balloon catheters in the porcine coronary restenosis model. Clin Res Cardiol. 2009;98:325–330.

40.

Hehrlein

Richardt

Wiemer

Description of Pantera Lux paclitaxel-releasing balloon and preliminary quantitative coronary angiography (QCA) results at six months in patients with coronary in-stent restenosis. EuroIntervention. 2011;7(Suppl K):K119–K124.

41.

Granada

Stenoien

Buszman

Mechanisms of tissue uptake and retention of paclitaxel-coated balloons: impact on neointimal proliferation and healing. Open Heart. 2014;1:e000117.

42.

Axel

Kunert

Goggelmann

Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation. 1997;96:636–645.

43.

Yazdani

Pacheco

Nakano

Vascular, downstream, and pharmacokinetic responses to treatment with a low dose drug-coated balloon in a swine femoral artery model. Catheter Cardiovasc Interv. 2014;83:132–140.

44.

De Labriolle

Pakala

Bonello

Paclitaxel-eluting balloon: from bench to bed. Catheter Cardiovasc Interv. 2009;73:643–652.

45.

Karnabatidis

Spiliopoulos

Katsanos

Below-the-knee drug-eluting stents and drug-coated balloons. Expert Rev Med Devices. 2012;9:85–94.

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