Latest Insights from the LEVANT II study and sub-group analysis Prof. Dr. med. Dierk Scheinert Division of Interventional Angiology University-Hospital Leipzig, Germany
Conflicts of Interest Advisory Board /Consultant: Abbott, Biotronik, Boston Scientific, Cook Medical, Cordis, CR Bard, Gardia Medical, Medtronic/Covidien, TriReme Medical, Trivascular, Upstream Peripheral Technologies 2
LEVANT 2 Study Design
Extensive Blinding Steps Taken to Reduce Bias Blinded Patient Core Labs Patient Core Labs DUS Tech Evaluating physician Patient Core Labs DUS Tech Evaluating physician Patient Core Labs DUS Tech Evaluating physician Randomization 30 days 6 months 12 months Not Blinded Treating Physician LEVANT 2 was designed to ensure blinding of the evaluating physician and DUS Tech at every phase including 30 days, 6 months, and 12 months
LEVANT 2 RCT (N=476) Primary Patency
Full Wall Apposition Showed Increased Primary Patency at 12 Months * LEVANT 2 Clinical Trial Average 0.9:1 Balloon to Artery Ratio LEVANT 2 Full Wall Apposition Sub Group 1.04: 1 Balloon to Artery Ratio A post-hoc subgroup analysis suggests the full wall apposition of the Lutonix 035 Drug Coated Balloon (minimum 1.04:1 balloon-to-artery ratio of the treatment device) showed increased primary patency of 79.9% (at 12 months Kaplan Meier, not pre-specified). Primary patency is defined as absence of binary restenosis defined by DUS PSVR 2.5 and freedom from Target Lesion Revascularization (TLR). Primary safety by treatment balloon / artery ratio <1 was 85.8% (DCB) and 82.1% (PTA). Primary safety by treatment balloon / artery ratio >1 was 79.3% (DCB) and 75.5% (PTA). Warning: Do not exceed Rated Burst Pressure. 6
Procedural Techniques for Optimal Drug Delivery Observations from LEVANT 2 suggest 12 month Primary Patency maybe positively influenced by Balloon Transit Time Balloon Inflation Pressure Balloon Inflation Time Final % Diameter Stenosis Indicators from Levant 2 Data Analysis
LEVANT 2 DCB Procedural Variable Analysis Final Residual Stenosis < 20% 74% 75% Inflation time 120 sec 65% 77% 79% n=28 82% 92% 84% n=22 n=19 n=12 85% n=27 62% 69% Pressure > 7 ATM 68% Post-hoc, sub-group analysis suggests that DCB 12 M Primary Patency may be: Improved with 3 variables Optimal with all 4 variables Transit time < 30 sec 65%
LEVANT 2 PTA Procedural Variable Analysis Final Residual Stenosis < 20% 59% Pressure > Levant 2 sub-group analysis n=29 7 ATM suggests that a similar effect was not observed with PTA 53% n=15 63% 44% n=32 n=45 Inflation time 120 sec
German Sub-Group Analysis
Angiographic Characteristics German vs. non-german Cohorts German Non-German Two Lesions Treated, % (n/n) 1.6% (2/126) 2.6% (9/350) DeNovo Target Vessel, % (n/n) 88.9% (112/126) 83.7% (293/350) Number of Patent Run-Off Vessels 1.7 ± 1.2 (126) 2.1 ± 0.9 (350) Reference Vessel Diameter (RVD), mm 4.8 ± 0.8 (126) 4.8 ± 0.8 (350) Lesion Length, mm 57.7 ± 41.0 (126) 64.7 ± 40.9 (349) Treated Length, mm 100.3 ± 45.5 (126) 110.6 ± 48.3 (350) Total Occlusions, % (n/n) 23.0% (29/126) 20.3% (71/350) Calcification, % (n/n) 60.3% (76/126) 58.3% (204/350) Severe Calcification, % (n/n) 11.1% (14/126) 9.1% (32/350) Most Distal Lesion Location, % (n/n) Proximal SFA 7.1% (9/126) 9.4% (33/350) Mid SFA 51.6% (65/126) 48.6% (170/350) Distal SFA 33.3% (42/126) 32.6% (114/350) Proximal Popliteal 2.4% (3/126) 5.4% (19/350) Mid Popliteal 4.8% (6/126) 3.1% (11/350) Distal Popliteal 0.8% (1/126) 0.9% (3/350)
Procedural Characteristics German vs. non-german Cohorts German Non-German Contralateral Access, % (n/n) 57.9% (73/126) 79.1% (277/350) Predilation Performed (All Lesions), % (n/n) 100.0% (126/126) 100.0% (350/350) Maximum %DS Post-Predilation, Pre-Treatment 41.8 ± 13.0 (121) 40.9 ± 13.1 (347) Total Paclitaxel on DCB Balloons Used per Subject (mg) 3.2 ± 1.6 (83) 3.7 ± 1.8 (233) Transit Time 21.8 ± 11.9 (105) 39.5 ± 29.3 (327) Inflation Time per Balloon (seconds) 129.8 ± 74.3 (157) 167.4 ± 91.7 (455) Max Pressure of Treatment Balloons (atm) 9.0 ± 2.2 (157) 7.7 ± 2.1 (455) Treatment Overstretch (inflated diameter/rvd) 0.9 ± 0.2 (106) 0.9 ± 0.2 (333) Dissections, % (n/n) Grade A 36.5% (46/126) 38.3% (133/347) Grade B 31.7% (40/126) 21.3% (74/347) Grade C 1.6% (2/126) 5.2% (18/347) Post-dilatation PTA, % (n/n) 17.5% (22/126) 22.3% (78/350) Provisional Bailout Stenting, % (n/n) 6.3% (8/126) 3.1% (11/350) Procedural Embolism, % (n/n) 1.6% (2/126) 0.9% (3/350) Diameter Stenosis (post-procedure), %DS 19.4 ± 10.4 (126) 21.5 ± 9.7 (349) Procedural Success (All Lesions), % (n/n) 90.5% (114/126) 87.4% (305/349)
Primary Patency (%) Primary Patency Kaplan Meier Efficacy, Primary Patency Lutonix DCB (N=83) Standard PTA (N=43) Difference P-value @365 days 79.4% 57.8% 21.6% 0.015 Time days Survival % Test DCB Events n at Risk n Survival % Control PTA Events n at Risk n log rank P 30 91.5% 7 74 88.1% 5 37 0.574 183 88.9% 9 68 76.2% 10 30 0.076 365 79.4% 16 50 57.8% 17 19 0.015
Freedom from TLR Kaplan Meier Efficacy, Primary Patency Lutonix DCB (N=83) Standard PTA (N=43) P-value @365 days 96.1% 82.0% 0.012 Time days Survival % Test DCB Events n at Risk n Survival % Control PTA Events n at Risk n log rank P 30 98.8% 1 80 100.0% 0 41 0.480 183 98.8% 1 76 92.6% 3 36 0.080 365 96.1% 3 63 82.0% 7 28 0.012
Global SFA Real-World Registry 12 Month Outcomes
Global SFA Registry Procedural Analysis Balloon Inflation Pressure * (ATM) Final % DS ** 20,9 9,7 7,8 14,6 LEVANT 2 (N=432) Global SFA (N=674) LEVANT 2 (N=316) Global SFA (N=680) * Maximum balloon pressure Mean ± sd (n) ** Maximum % DS Mean ± sd (n)
Lutonix Global SFA Real-World Registry 12 Month Results Measure Lutonix DCB % (n/n) Freedom from TLR 94.3% (595/631) 30 Day Safety 99.7% (677/678)
Lutonix Global SFA Real-World Registry Sub-group Analysis Long Lesions (140 500 mm)
Baseline Lesion Characteristics All Lesions vs Long Lesions (140 500 mm) All Lesions (23 500 mm) Long Lesions (140 500 mm) Total Lesion Length (mm) 101.2 ± 84.2 (685) 212.3 ± 65.3 (140) Treated Length (mm) 136.6 ± 89.7(685) 235.8 ± 74.0 (140) Calcification, % (n/n) 50.2% (238/474) 57.5% (46/80) Total Occlusion, % (n/n) 31.2% (214/686) 42.1% (59/140) Lesion Locations, % (n/n) SFA, % (n/n) 70% (483/690) 66.4% (93/140) Proximal Popliteal, % (n/n) 16.8% (116/690) 15.7% (22/140) Mid & Distal Popliteal, % (n/n) 13.1% (91/690) 17.9% (25/140) %DS post-treatment, % 14.6 ± 18.7 (680) 19.0 ± 21.0 (140) Bail-out Stenting, % (n/n) 25.3% (174/689) 35.7% (50/140) Dissection, % (n/n) 30.1% (135/448) 34.3% (48/140)
12 Month Results All Lesions vs Long Lesions (140 500 mm) Measure All Lesions % (n/n) Long Lesions % (n/n) Freedom from TLR 94.3% (595/631) 93.7% (119/127) 30 Day Safety 99.7% (677/679) 100.0% (138/138)
12 Month Sub-group Analysis All Lesions vs Long Lesions (140 500 mm) Sub-group All Lesions % (n/n) Freedom from TLR Long Lesions % (n/n) Calcification 95.9% (213/222) 97.6% (41/42) CTO 94.8% (184/194) 100.0% (51/51)
12 Month Sub-group Analysis Long Lesions >25cm Sub-Group Freedom from TLR Long Lesions % (n/n) Lesions >25cm 94.0% (47/50) Lesions >25cm - No Bailout Stent 96.0% (24/25) Lesions >25cm - With Bailout Stent 92.0% (23/25) 22
Summary LEVANT 2 post-hoc sub-group analysis suggests that DCB 12 M Primary Patency maybe influenced by balloon Transit time, Inflation Pressure, Inflation Time and Final % Diameter Stenosis LEVANT 2 German cohort suggest that good DCB procedures result in durable long term clinical benefits Global SFA Registry showed favorable Freedom from TLR of at 12 months, including in: females, calcified lesions and CTOs Long Lesions (140 500 mm) Global SFA Regisry interim data suggest sustained benefits at 24 months 23
Latest Insights from the LEVANT II study and sub-group analysis Prof. Dr. med. Dierk Scheinert Division of Interventional Angiology University-Hospital Leipzig, Germany