No Mortality Signal With Stellarex Low-Dose Paclitaxel DCB: ILLUMENATE Pivotal 4-Year Outcomes.

BACKGROUND: Paclitaxel-coated balloons have shown safety and efficacy in the short- to intermediate-term; however, long-term data remain limited. OBJECTIVES: To report late safety and efficacy outcomes for a low-dose paclitaxel drug-coated balloon (DCB) compared with percutaneous transluminal angioplasty (PTA) in femoropopliteal lesions from a large randomized controlled trial (RCT). METHODS: ILLUMENATE Pivotal is a multicenter, single-blind RCT conducted across 43 US and EU centers to examine the safety and efficacy of the Stellarex DCB for the treatment of femoropopliteal disease. Assessments were recorded for all active patients at 36 and 48 months. Vital status of patients formally exited from the study was also collected. RESULTS: Primary patency through 36 months for patients treated with DCB was significantly higher compared with PTA (p=0.016). The primary safety endpoint through 36 months was 77.4% and 72.4%, respectively (p=0.377). Kaplan-Meier analysis indicated that a higher proportion of DCB subjects were event-free compared with PTA at all study visits. The rate of major adverse event (MAE) through 48 months was 32.9% in the DCB group and 37.9% in the PTA group (p=0.428). No differences in the rate of mortality were evident through 48 months of follow-up with 15.6% in the DCB group and 15.2% in the PTA group (p=0.929). CONCLUSIONS: Stellarex DCB was associated with significantly higher patency compared with PTA through 3 years with no mortality difference detected through 4 years. The data from the ILLUMENATE Pivotal RCT support the long-term safety and efficacy of the low-dose Stellarex DCB.

The RANGER II superficial femoral artery trial: 1-year results of the long lesion cohort.

BACKGROUND: The objective of the RANGER II SFA long lesion cohort analysis was to evaluate the safety and effectiveness of the Ranger drug-coated balloon (DCB) in patients with lesion lengths greater than 100 mm. METHODS: Patients from the RANGER II SFA randomized controlled trial and long balloon sub-study were included in the long lesion cohort if their baseline lesion measurement was > 100 mm and if they had been treated with a RANGER DCB. Patients had symptomatic lower limb peripheral artery disease and Rutherford classification 2-4 symptomatology. The endpoints of interest included the 12-month target lesion primary patency and freedom from major adverse events (MAEs).Additional patient outcomes including changes in Rutherford classification were also evaluated. RESULTS: A total of 129 patients met the inclusion criteria and were included in the long lesion cohort. Mean lesion length was 144.5 ± 31.7 mm. Seventy-five lesions had Peripheral Arterial Calcium Scoring System (PACSS) grades 3 (33.3%, 43/129) and 4 (24.8%, 32/129). The Kaplan-Meier estimate of the primary patency rate at 12 months was 88.0%. The rate of freedom from MAEs at 12 months was 95.1% (117/123; 95% CI: 89.7%, 98.2%); all MAEs were clinically driven target lesion revascularization (4.9%, 6/123). The 12-month mortality rate was 2.4% (3/125). CONCLUSIONS: Patients with lesions > 100 mm treated with Ranger DCBs demonstrated excellent 1-year safety and efficacy results, comparable to those of the overall RANGER II SFA randomized clinical trial. This suggests that the Ranger DCB can provide consistent results regardless of lesion length. (ClinicalTrials.gov Identifier: NCT03064126).

Directional atherectomy before paclitaxel coated balloon angioplasty in complex femoropopliteal disease: The VIVA REALITY study.

BACKGROUND: Drug coated balloon (DCB) angioplasty significantly reduces reintervention rates in patients with symptomatic femoropopliteal peripheral artery disease (PAD). However, stand-alone DCB use in long, severely calcified lesions is frequently associated with vessel recoil and/or high-grade dissections necessitating provisional stent implantation. OBJECTIVES: Assess the safety and effectiveness of a vessel preparation strategy with directional atherectomy (DA) prior to DCB angioplasty in patients with symptomatic severely calcified femoropopliteal PAD. METHODS: REALITY (NCT02850107) prospectively enrolled subjects at 13 multinational centers with 8-36 cm femoropopliteal stenoses or occlusions with bilateral vessel wall calcification treated with DA prior to DCB angioplasty. The primary effectiveness endpoint was 12-month primary patency, and the primary safety endpoint was freedom from major adverse events through 30 days. Independent angiographic and duplex core laboratories assessed outcomes and a Clinical Events Committee adjudicated events. RESULTS: A total of 102 subjects were enrolled; one lesion was treated per subject. The mean lesion length was 17.9 ± 8.1 cm, 39.0% were chronic total occlusions (mean lesion length 22.6 ± 8.6 cm); 86.2% of lesions exhibited moderate to severe bilateral calcification. Provisional stents were implanted in 8.8% (9/102) of subjects. Twelve-month primary patency rate was 76.7% (66/86) and freedom from CD-TLR rate was 92.6% (87/94). No device or procedure related deaths and one index-limb major amputation were reported. CONCLUSIONS: Plaque excision with DA in patients with symptomatic severely calcified femoropopliteal arterial disease prior to DCB angioplasty is a safe and effective treatment strategy with a low provisional stent rate.

Stellarex Drug-Coated Balloon for Treatment of Femoropopliteal Disease: Twelve-Month Outcomes From the Randomized ILLUMENATE Pivotal and Pharmacokinetic Studies.

BACKGROUND: Drug-coated balloons (DCBs) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Because of the differences in excipients, paclitaxel dose, and coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of 2 studies investigating the pharmacokinetic and clinical outcomes of a new DCB to treat femoropopliteal disease. METHODS: In the ILLUMENATE Pivotal Study (Prospective, Randomized, Single-Blind, U.S. Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon), 300 symptomatic patients (Rutherford class 2-4) were randomly assigned to DCB (n=200) or standard angioplasty (percutaneous transluminal angioplasty [PTA]) (n=100). The primary safety end point was freedom from device- and procedure-related death through 30 days, and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months. The primary effectiveness end point was primary patency through 12 months. In the ILLUMENATE PK study (Pharmacokinetic Study of the Stellarex Drug-Coated Angioplasty Balloon), paclitaxel plasma concentrations were measured after last DCB deployment and at prespecified times (at 1, 4, 24 hours and at 7 and 14 days postprocedure) until no longer detectable. RESULTS: In the ILLUMENATE Pivotal Study, baseline characteristics were similar between groups: 50% had diabetes mellitus, 41% were women, mean lesion length was 8.3 cm, and 44% were severely calcified. The primary safety end point was met (92.1% for DCB versus 83.2% for PTA, P=0.025 for superiority) and the primary patency rate was significantly higher with DCB (76.3% for DCB versus 57.6% for PTA, P=0.003). Primary patency per Kaplan-Meier estimates at day 365 was 82.3% for DCB versus 70.9% for PTA (P=0.002). The rate of clinically driven target lesion revascularization was significantly lower in the DCB cohort (7.9% versus 16.8%, P=0.023). Improvements in ankle-brachial index, Rutherford class, and quality of life were comparable, but the PTA cohort required twice as many revascularizations. Pharmacokinetic outcomes showed that all patients had detectable paclitaxel levels after DCB deployment that declined within the first hour (54.4±116.9 ng/mL to 1.4±1.0 ng/mL). CONCLUSIONS: The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA, and plasma levels of paclitaxel fall to low levels within 1 hour. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifiers: NCT01858428 and NCT01912937.

Determinants of Drug-Coated Balloon Failure in Patients Undergoing Femoropopliteal Arterial Intervention.

BACKGROUND: Drug-coated balloons (DCB) are frequently used to treat femoropopliteal artery disease. However, patency loss occurs in ≥10% of patients within 12 months posttreatment with poor understanding of the underlying mechanisms. OBJECTIVES: The authors sought to investigate the determinants of DCB failure in femoropopliteal disease. METHODS: Data from randomized clinical trials (IN.PACT SFA, MDT-2113 SFA Japan) and 2 prespecified imaging cohorts of the IN.PACT Global Clinical Study were included. Influential procedural characteristics were evaluated by an independent angiographic core laboratory. The primary endpoint was DCB failure (patency loss during follow-up). Additional endpoints were binary restenosis and clinically driven target lesion revascularization. Multivariable analyses evaluated the clinical, anatomical, and procedural predictors of DCB failure. RESULTS: Included were 557 participants with single lesions and 12-month core laboratory-adjudicated duplex ultrasonography. Key clinical characteristics were as follows: mean age 68.8 years, 67.5% male, 87.6% with hypertension, 76.9% with hyperlipidemia, 40.5% with diabetes mellitus, 90.5% in Rutherford Classification Category (RCC) 2 to 3, and 9.5% in RCC 4 to 5. Average length and reference vessel diameter (RVD) were 16.37 cm and 4.66 mm, respectively; 49.7% of lesions were totally occluded. In multivariable analysis, only residual stenosis >30% was associated with patency loss, whereas residual stenosis >30% and smaller preprocedure RVD were associated with increased binary restenosis risk. RCC >3 and residual stenosis >30% were associated with increased 12-month clinically driven target lesion revascularization risk. CONCLUSIONS: Patency loss after DCB treatment was influenced by procedural and clinical factors. Residual stenosis >30%, smaller preprocedure RVD, and higher RCC may be considered predictors of increased risk of DCB failure and its components in femoropopliteal artery disease. (Randomized Trial of IN.PACT Admiral® Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I]; NCT01175850; IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II]; NCT01566461; MDT-2113 Drug-Eluting Balloon vs. Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery [MDT-2113 SFA]; NCT01947478; IN.PACT Global Clinical Study; NCT01609296).

1-Year Results From the RANGER II SFA Randomized Trial of the Ranger Drug-Coated Balloon.

OBJECTIVES: This study sought to evaluate the safety and effectiveness of the Ranger drug-coated balloon (DCB) (paclitaxel dose density 2 µg/mm2) for treating superficial femoral artery or proximal popliteal artery lesions. BACKGROUND: Paclitaxel-coated balloon treatment prevents reinterventions, but dose and coating characteristics differ among balloons and necessitate discrete confirmation of safety and effectiveness. METHODS: Patients with symptomatic lower limb ischemia (Rutherford classification 2 to 4) were randomized 3:1 to treatment with the Ranger DCB or standard percutaneous transluminal angioplasty (PTA). Twelve-month primary target lesion patency, freedom from major adverse events (i.e., target lesion revascularization, major amputations, death within 1 month of the index procedure), and patient outcomes were analyzed. RESULTS: Mean lesion length was 82.5 ± 48.9 mm for the Ranger DCB group (n = 278) and 79.9 ± 49.3 mm for the control group (n = 98). Ranger DCB was superior to PTA (82.9% [n = 194 of 234] vs. 66.3% [n = 57 of 86]) with observed 12-month primary patency rates yielding a difference of 16.6% (95% confidence interval: 5.5% to 27.7%; p = 0.0013). Noninferior freedom from major adverse events (94.1% [n = 241 of 256] vs. 83.5% [n = 76 of 91]) was demonstrated with a difference of 10.6% (95% confidence interval: 2.5% to 18.8%; noninferiority p < 0.0001). Primary patency rate curves showed significant separation by Kaplan-Meier analysis (log-rank p = 0.0005), with rates of 89.8% and 74.0% estimated at day 365 for the Ranger DCB and PTA cohorts, respectively. CONCLUSIONS: The low-dose Ranger DCB demonstrated significantly better effectiveness than standard PTA through 1 year and a good safety profile. (Ranger™ Paclitaxel Coated Balloon vs Standard Balloon Angioplasty [RANGER II SFA]; NCT03064126).

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.

BACKGROUND: Randomized controlled trials have reported favorable 1-year outcomes with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral arterial disease when compared with standard percutaneous transluminal angioplasty (PTA). Evidence remains limited on the durability of the treatment effect with DCBs in the longer term. METHODS AND RESULTS: IN.PACT SFA is a single-blind, randomized trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 patients with symptomatic (Rutherford 2-4) femoropopliteal lesions up to 18 cm in length. Patients were randomized 2:1 to receive treatment with DCB or PTA. The 36-month assessments included primary patency, freedom from clinically driven target lesion revascularization, major adverse events, and functional outcomes. At 36 months, primary patency remained significantly higher among patients treated with DCB compared with PTA (69.5% versus 45.1%; log rank P<0.001). The rates of clinically driven target lesion revascularization were 15.2% and 31.1% (P=0.002) for the DCB and PTA groups, respectively. Functional outcomes were similarly improved between treatment groups even though subjects in the DCB group required significantly fewer reinterventions versus those in the PTA group (P<0.001 for target lesion revascularization, P=0.001 for target vessel revascularization). There were no device- or procedure-related deaths as adjudicated by an independent Clinical Events Committee. CONCLUSIONS: Three-year results demonstrate a durable and superior treatment effect among patients treated with DCB versus standard PTA, with significantly higher primary patency and lower clinically driven target lesion revascularization, resulting in similar functional improvements with reduced need for repeat interventions. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01175850 for IN.PACT SFA phase I in the European Union and NCT01566461 for IN.PACT SFA phase II in the United States.