New developments in the clinical use of drug-coated balloon catheters in peripheral arterial disease

Figures & data

Table 1 Baseline clinical and angiographic measures for femoropopliteal studies

Trial	Enrollment period	Patients randomized (n)	DCB	Inclusion criteria	Exclusion criteria	Follow-up period	Outcomes measured	Baseline RC	Total occlusions	Lesion length	Stent placement
THUNDER^Citation24	2004–2005	102 (48 DCB vs 54 PTA)	Standard balloons coated with paclitaxel (PACCOCATH coating) (3 mg/mm^2 balloon surface)	One vessel with >70% stenosis, >2 cm length in SFA/Pop	Poor inflow. No outflow, acute presentation, pregnancy, life expectancy <1 year	6-month angiogram follow-up 6, 12, and 24 months clinical follow-up	LLL and MAE at 6 months	DCB 3.4; PTA 3.1	DCB 27%; PTA 26%	DCB 7.5 cm; PTA 7.4 cm	DCB 17%; PTA 11%
THUNDER^Citation25 5 year	2004–2005	102 (48 DCB and 54 PTA) of which 30 patients had 5-year follow-up data	Standard balloons coated with paclitaxel (PACCOCATH coating) (3 mg/mm^2 balloon surface)	One vessel with >70% stenosis, >2 cm length in SFA/Pop	Poor inflow. No outflow, acute presentation, pregnancy, life expectancy <1 year	2–5 years postoperative clinical follow-up	TLR	DCB 3.4; PTA 3.1	DCB 27%; PTA 26%	DCB 7.5 cm; PTA 7.4 cm	DCB 17%; PTA 11%
LEVANT1^Citation27	2009–2009	75 randomized to DCB vs PTA after standard angioplasty	Lutonix (2 mg/mm^2 balloon surface polysorbate/sorbitol)	Symptomatic with one lesion >70% stenosis, 4–15 cm in length, vessel diameter 4–6 cm	Severe calcification, inflow disease, or absence of ≥1 runoff vessel	1, 6, 12, and 24-month clinical follow-up. Angiogram at 6 months	LLL at 6 months, CD-TLR at 1, 6, 12, and 24 months	RC 2/3/4/5; DCB 22%/72%/2%/4%; PTA 21%/71%/4%/4%	DCB 41%; PTA 42%	DCB 80.8±37.0 mm; PTA 80.2±37.8 mm	DCB 27%; PTA 38%
LEVANT2^Citation28	2011–2012	476 randomized 2:1 to DCB vs PTA	Lutonix (2 mg/mm^2 balloon surface polysorbate/sorbitol)	Symptomatic claudication, RC 2–4 with >70% stenosis in SFA or Pop length <15 cm and diameter 4–6 cm	Need for stent post predilation angioplasty	1, 6, and 12-month clinical follow-up	Primary patency, death, amputation	RC 2/3/4; DCB 29%/63%/8%; PTA 34%/58%/8%	DCB 21%; PTA 21.9%	DCB 62.7±41 mm; PTA 63.2±40.4 mm	DCB 2.5%; PTA 6.9%
DEBATE- SFA^Citation31	2010–2011	104 randomized to DCB + BMS or PTA + BMS	IN.PACT Admiral (3 mg/mm^2 balloon surface) and urea as hydrophilic natural spacer	Claudication with >70% stenosis, >4 cm length in SFA/Pop with at least one patent infrapopliteal vessel	Life expectancy <1 year, preprocedure need for amputation	12-month angiogram	Binary restenosis by angiogram or US PSV ratio>2.4 (primary) and TLR (secondary)	RC 3/4/5/6; DCB 21/21/55/496; PTA 31/22/41/696	DCB 55%; PTA 69%	DCB 94 mm; PTA 96 mm	DCB 100%; PTA 100%
PACIFIER^Citation29	2010–2012	85; 44 DCB vs 41 Pacific Xtreme (PTA)	IN.PACT Pacific (3 mg/mm^2 balloon surface) and urea as hydrophilic natural spacer	Claudication with >70% stenosis of SFA/Pop, length 3–30 cm	Inflow disease, significant three-vessel infrapopliteal disease	6-month angiogram. 6 and 12-month clinical follow-up	LLL at 6 months, CD-TLR at 6 and 12 months	RC 2/3/4/5; DCB 9%/86%/0%/4.5%; PTA 13%/83%/43%/0%	DCB 22.7%; PTA 38.3%	DCB 7 cm; PTA 6.3 cm	DCB 20.5%; PTA 34%
IN.PACT SFA^Citation33	2010–2013	331 randomized 2:1 DCB vs PTA	IN.PACT Admiral (3.5 mg/mm^2 balloon surface) and urea as hydrophilic natural spacer	RC 2–4, >70% stenosis of SFA/Pop, 4-18 cm if no occlusion, < 10 cm If total occlusion	Inflow disease, significant three-vessel infrapopliteal disease	1, 6, and 12-month clinical follow-up	Primary patency at 12 months	RC 2/3/4/5; DCB 38%/57%/5%/0%; PTA 38%/56%/5%/1%	DCB 25.8%; PTA 19.5%; P=0.22	DCB 8.94±4.89 cm; PTA 8.81±5.12 cm	DCB 7.3%; PTA 12.6%
IN.PACT SFA 2 year^Citation32	2010–2013	331 randomized 2:1 DCB vs PTA (evaluation complete for DCB 170 and PTA 94)	IN.PACT Admiral (3.5 mg/mm^2 balloon surface) and urea as hydrophilic natural spacer	RC 2-4, >70% stenosis of SFA/Pop, 4–18 cm if no occlusion, <10 cm if total occlusion	Inflow disease, significant three-vessel infrapopliteal disease	12- to 24-month clinical follow-up	Primary patency, freedom from CD-TLR	RC 2/3/4/5; DCB 38%/57%/5%/0%; PTA 38%/56%/5%/1%	DCB 25.8%; PTA 19.5%; P=0.22	DCB 8.94±4.89 cm; PTA 8.81±5.12 cm	DCB 7.3%; PTA 12.6%
BIOLUX-P1^Citation34	2010–2011	60 patients randomized 1:1 DCB vs PTA	Passeo 18- Lux Balloon (3 mg/mm^2 balloon surface) with BTHC excipient	RC 2–5, >70% stenosis of SFA/Pop, 3–20 cm lesion length	Thrombus present, <1 patent infrapopliteal vessel, prior stent at target lesion, prior bypass graft, severe calcification	6-month angiogram. 6 and 12-month clinical follow-up	Primary – LLL at 6 months Secondary –BR and CD-TLR at 6 and 12 months	RC 2/3/4/5; DCB 23/57/13/7; PTA 30/57/7/7	38.2% of entire cohort	DCB 51.4±47.2 mm; PTA 68.5±57.0 mm; P=0.31	DCB 6.7%; PTA 26.7%; P=0.038

Note: Primary patency, freedom from binary restenosis by US or TLR.

Abbreviations: BMS, bare metal stent; BR, binary restenosis; BTHC, n-butyryl-tri-n-hexyl citrate; CD-TLR, clinically driven target lesion revascularization; DCB, drug-coated balloon; LLL, late lumen loss; MAE, major adverse event; Pop, popliteal artery; PSV, peak systolic velocity; PTA, percutaneous transluminal angioplasty; RC, Rutherford classification; SFA, superficial femoral artery; TLR, target lesion revascularization; US, ultrasound.

Table 2 Primary and secondary outcomes for femoropopliteal studies

Trial	Primary patency	LLL	RC improvement at follow-up	ABI change	BR	TLR	MAE
THUNDER^Citation24	NA	DCB 0.4±1.2 mm; PTA 1.7±1.8 mm; P<0.001	DCB 1.2; PTA 1.6; P=0.92	DCB 0.9; PTA 0.8; P=0.79	DCB 17%; PTA 44%; P=0.01	12/24 months; DCB 10%/15%; PTA 48%/52%; P<0.001/0.001	None
THUNDER 5 years^Citation25	NA	DCB 0.7+1.5 mm; PTA 1.5±1.3 mm; P=0.54	NA	NA	DCB 17%; PTA 54%; P=0.04	DCB 21%; PTA 56%; P<0.0005	None
LEVANT1^Citation27	NA	DCB 0.46 mm; PTA 1.09 mm; P=0.016	6/12/24 months; DCB 1.7/1.6/2.1; PTA 1.6/2.1/1.8	6/12/24 months; DCB 0.2/0.18/0.2; PTA 0.22/0.2/0.18	NA	6/12/24 months; DCB 13%/29%/36%; PTA 24%/37%/51%; P=0.23	No difference between groups
LEVANT2^Citation28	DCB 65.2%; PTA 52.6%; P=0.02	NA	12 months; DCB 1.9; PTA 1.7; P=NS	12 months; DCB 0.17; PTA 0.18; P=NS	DCB 62%; PTA 65%; P=NS	12 months; DCB 38%; PTA 37.5%; P=NS	DCB 16%; PTA 21%; P=NS
DEBATE- SFA^Citation31	NA	DCB 0.86 mm; PTA 1.68 mm; P<0.001	RC delta ≥2; DCB 81.8%; PTA 54.5%; P=0.02	NA	DCB 17%; PTA 47.3%; P=0.008	12 months; DCB 17%; PTA 33.3%; P=0.07	None
PACIFIER^Citation29	NA	DCB −0.01 mm; PTA 0.65 mm; P=0.001	Improvement in RC >1; DCB 80%; PTA 68%	NA	DCB 8.6%; PTA 32.4%; P=0.01	6/12 months; DCB 7.1%/7.1%; PTA 26.2%/34.9%; P=0.01/0.01	Death, amputation, TLR; DCB 7.1%; PTA 34.9%; P=0.003
IN.PACT SFA^Citation33	DCB 82.2%; PTA 52.4%; P<0.001	NA	Sustained clinical improvement; DCB 85%; PTA 67%; P<0.001	DCB 0.95; PTA 0.89; P=0.002	NA	DCB 2.4%; PTA 20.6%; P<0.001	No difference
IN.PACT SFA 2 years^Citation32	DCB 78.9%; PTA 50.1%; P<0.001	NA	Sustained clinical improvement; DCB 77%; PTA 59%; P=0.003	DCB 0.92; PTA 0.94; P=0.611	DCB 19.8%; PTA 46.9%; P<0.01	DCB 9.1%; PTA 28.3%; P<0.001	Safety composite: DCB 87.4%; PTA 69.4%; P<0.001; MAE: DCB 19.2%; PTA 31.1%; P=0.02
BIOLUX-P1^Citation34	NA	DCB 0.51±0.72 mm; PTA 1.04±1.00 mm; P=0.033	RC improvement >1; DCB 72%; PTA 65.2%; P=NS	DCB 0.9±0.2; PTA 1.0±0.2	DCB 11.5%; PTA 34.6%; P=0.048	DCB 15.4%; PTA 41.7%; P=0.06	DCB 19.2%; PTA 41.2%; P=0.14

Note: Primary patency, freedom from binary restenosis by US or TLR.

Abbreviations: ABI, ankle–brachial index; BR, binary restenosis; DCB, drug-coated balloon; LLL, late lumen loss; MAE, major adverse event; NA, not available; NS, not significant; PTA, percutaneous transluminal angioplasty; RC, Rutherford classification; SFA, superficial femoral artery; TLR, target lesion revascularization; US, ultrasound.

Table 3 Baseline clinical and angiographic measures for BTK studies

Trial	Enrollment period	No of patients randomized	DCB	Inclusion criteria (all CLI)	Exclusion criteria	Follow-up period	Outcomes measured	Baseline RC	Total occlusions	Lesion length (mm)
Schmidt et al^Citation46	2009–2010	Nonrandomized, 104 patients	IN.PACT Amphirion (FreePac coating) (3 mg/mm^2 balloon surface, urea excipient)	Tibial vessel(s) with >70% stenosis, >8 cm length	NA, not listed	3-month angiographic; 3- and 12-month clinical	BR and clinical improvement (≥50% ulcer reduction or increase of at least one RC	4.5	61.90%	173±87
Debate BTK^Citation47	2010–2011	132 randomized l:l to DCB vs PTA	IN.PACT Amphirion (FreePac coating) (3 mg/mm^2 balloon surface, urea excipient)	Diabetes, tibial vessel(s) with >70% stenosis, >4 cm length, with distal runoffa	Allergy to paclitaxel, planned major amputation, life expectancy <1 year	12-month clinical and angiographic (or DUS)	BR, CD-TLR, amputation, and TVO	DCB 5.15; PTA 5.09	DCB 77.5%; PTA 82.1%	DCB 129±83; PTA 131±79
IN. PACT DEEP^Citation48	2009–2012	358 randomized 2:1 to DCB vs PTA (all clinical cohort, 167 angiographic cohort)	IN.PACT Amphirion (FreePac coating) (3 mg/mm^2 balloon surface, urea excipient)	Tibial vessel(s) >70% stenosis any length, with distal runoff.a Angiogram cohort lesion <10 cm.	Inflow lesion >15 cm length, failure to cross TL with 0.014′ wire, planned major amputation, failure to obtain <30% postprocedure residual stenosis	1, 6, and 12-month clinical follow-up; ±12-month angiography	CD-TLR, LLL, primary safety composite	DCB 4.87; PTA 4.85	DCB 38.6%; PTA 45.9%	DCB 102±91; PTA 129±95; angiogram cohort: DCB 59.1±41.7; PTA 79.7±74.6
BIOLUX P-II^Citation50	2012–2014	72 randomized 1:1 to DCB vs PTA	Passeo-18 Lux DEB (3 mg/mm^2 balloon surface, BTHC excipient)	Tibial vessel(s) with >70% stenosis, >3 cm, with distal runoffa	Need for stent postprediction angioplasty	1, 6, and 12-month clinical follow-up; 6-month angiography	Primary safety composite and 6-month target lesion primary patency	DCB 4.5; PTA 4.4	Not reported	DCB 113.1±88.1; PTA 115.0±86.9

Notes:

a Distal runoff: at least one tibial vessel with runoff to the foot. Target vessel may have direct or collateral runoff.

Abbreviations: BR, binary restenosis; BTHC, n-butyryl tri-n-hexyl citrate; BTK, below the knee; CLI, critical limb ischemia; CD-TLR, clinically driven target lesion revascularization; DCB, drug-coated balloon; LLL, late lumen loss; NA, not available; PTA, percutaneous transluminal angioplasty; RC, Rutherford classification; TL, target lesion; TVO, target vessel occlusion; DUS, Doppler ultrasound.

Table 4 Primary and secondary outcomes for BTK studies

Trial	Primary patency	LLL (mm)	BR	Clinical improvement or RC at follow-up	ABI	TLR	MAEs
Schmidt et al^Citation46 (Single Center Leipzig Registry)	3 months: 72.6%	NA	27.4%: 19.1% restenosis and 8.3% target vessel occlusion	Clinical improvement 91.2%, complete wound healing 74.2% of RC 5 patients	NA	17.3%	Four amputations (two major, two minor)
Debate BTK^Citation47	NA	NA	DCB: 27.0%; PTA: 74.3% (P<0.001)	DCB: 0.90±1.8; PTA: 2.0±2.3 (P<0.004)	DCB: 0.78±0.22; PTA: 0.47±0.28	DCB: 18%; PTA: 43% (P=0.002); TVO–DCB: 17%; PTA: 55% (P<0.001)	DCB: 31%; PTA: 51% (P=0.02) – driven by TLR and wound healing, amputation–DCB: 0%; PTA: 1.5% (P=0.0005)
IN.PACT DEEP^Citation48	NA	DCB: 0.61±0.78 mm; PTA: 0.62±0.78 mm (P=0.950)	DCB: 41.0%; PTA: 35.5% (P=0.609)	NA	NA	CD-TLR; DCB: 9.2%; PTA: 13.1% (P=0.291)	6-month primary safety composite – DCB: 17.7%; PTA: 15.8%; 12-month major amputation – DCB: 8.8%; PTA: 3.6%
BIOLUX P-II^Citation50	DCB 65.2%; POBA 52.6%; P=0.02	DCB: 0.56±0.65 mm; PTA: 0.54±0.66 mm (P=0.913)	DCB: 53.1%; PTA: 41.4% (P=0.359)	DCB: 2.3±2.3; PTA: 2.7±2.4 (P>0.05)	12-month DCB: 1.0±0.2; PTA: 0.9±0.2 (P=0.327)	CD-TLR; DCB: 31.3%; PTA: 26.9% (P=0.805)	12-month MAE composite; DCB: 41.1%; PTA: 39.1% (P=0.957)

Abbreviations: ABI, ankle–brachial index; BR, binary restenosis; BTK, below-the-knee; CD-TLR, clinically driven target lesion revascularization; DCB, drug-coated balloon; LLL, late lumen loss; MAE, major adverse event; NA, not available; POBA, plain old balloon angioplasty; PTA, percutaneous transluminal angioplasty; RC, Rutherford classification; TLR, target lesion revascularization; TVO, target vessel occlusion.

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