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Insights from the IN.PACT Global Study 3-year Data: Does Lesion
Complexity Affect Results?
Jos van den Berg, MD
Ospedale Civico Lugano
Lugano, Switzerland
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Speaker name:
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I have the following potential conflicts of interest to report:
Receipt of grants/research support
Receipt of honoraria and travel support
Participation in a company sponsored speakers‘ bureau
Employment in industry
Shareholder in a healthcare company
Owner of a healthcare company
I do not have any potential conflict of interest
Disclosure
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x
Background Randomized trials report superior safety and effectiveness of drug-coated
balloons (DCB) over percutaneous angioplasty (PTA),1-4 however the inclusion criteria for these IDE trials are not representative of the more complex lesions typically found in the treatment of femoropopliteal disease
Global DCB studies and registries report outcomes for the use of DCB in more complex, real-world populations5-10 and one study has reported 3 year outcomes11
Previous 1 year results of the IN.PACT Global Standard vs. Broader use analysis of the IN.PACT Admiral DCB reported safe and effective in more complex lesions typically excluded form randomized trials12 however, longer term outcomes from Global Studies are needed.
1. Tepe G. et al. Circulation. 20152. Laird J. et al. JACC. 20153. Schneider P. et al. Circ-CI. 20184. Rosenfield K. et al. NEJM. 20155. Thieme M. JACC-CI. 20176. Schroe H. et al. CCI. 2018
7. Scheinert D, et al. Circ-CI. 20188. Tepe G, CX London, UK 20169. Brodmann M, et al. JACC-CI. 201710. Micari A, et al. JACC-CI. 201811. Tepe G. CIRSE 201812. Ansel G. et al. JEVT. 2018
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Ansel G. et al. JEVT. 2018
https://doi.org/10.1177/1526602818803
IN.PACT Global Study
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IN.PACT Global Study Architecture
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1Y T. Zeller Circ-CI 2019
3Y CIRSE 2018 G. Tepe
IN.PACT Global Study: Primary Endpoints
Efficacy
• 12-month Freedom from clinically-driven TLR − Any re-intervention within the target lesion(s) due to symptoms
or drop of ABI of ≥ 20% or > 0.15 when compared to post-index procedure baseline ABI
• Composite− 30-day freedom from device- and procedure-related mortality and
12-month freedom from major target limb amputation and clinically-driven TVR
Safety
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IN.PACT Global Study: Standard vs. Broader Use
Objective: Substantiate consistent and durable performance of the IN.PACT AdmiralDCB in a real-world population with complex lesions by comparing results from an ad-hoc analysis of IN.PACT Global Clinical Cohort Standard DCB use vs Broader DCB use.
Defined as complex patients and lesions, typically excluded from pivotal trials, including:
• Bilateral lesions• Multiple lesions• Calcium (moderate to
severe)• All subjects that do not
meet the “Standard Use” criteria
Standard DCB Use
Defined as IDE-like patients and lesions typical of pivotal trials, including:
• Simple de novo lesions, lesion length ≤ 18 cm
• Single lesion• Total occlusions ≤ 10 cm• Calcium (none to mild)• Excluding In-stent
restenosis
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Broader DCB Use
vs
IN.PACT Global Study: Standard vs. Broader UseBaseline Clinical Characteristics
CharacteristicsIN.PACT Global
Standard Use DCB N= 281 Subjects
IN.PACT Global Broader Use DCBN= 1125 Subjects
P-value
Age (Y, Mean ± SD) 67.2 ± 10.4 68.9 ± 10.0 0.012
Male (%) 63.3% (178/281) 68.9% (775/1125) 0.087
Diabetes (%) 36.6% (102/279) 40.8% (458/1123) 0.219
Hypertension (%) 76.7% (214/279) 85.1% (955/1122) 0.001
Hyperlipidemia (%) 68.8% (185/269) 70.9% (775/1093) 0.502
Current Smoker (%) 38.1% (107/281) 30.2% (340/1125) 0.012
Obesity (BMI ≥ 30 kg/m², %) 18.6% (52/279) 21.0% (233/1112) 0.408
Coronary Heart Disease (%) 33.1% (87/263) 42.4% (453/1069) 0.006
Carotid Artery Disease (%) 17.2% (41/238) 20.9% (200/958) 0.240
Renal Insufficiency1 (%) 8.6% (21/245) 11.8% (115/972) 0.173
Previous Peripheral Revasc (%) 37.7% (106/281) 56.1% (631/1125) < 0.001
Concomitant BTK Disease (%) 42.4% (108/255) 46.1% (486/1055) 0.294
ABI2 (Mean ± SD) 0.695 ± 0.229 0.674 ± 0.215 0.157
1. Baseline serum creatinine ≥1.5 mg/dL.2. ABI for all target limbs treated during the 1st index procedure are included (can be bilateral) 9
IN.PACT Global Study: Standard vs. Broader UseRutherford Clinical Category
38%
54%
8%
IN.PACT Global Standard Use DCB
RCC 2 RCC 3 RCC 4
29%
59%
9%3%
IN.PACT GlobalBroader Use DCB
RCC 1 RCC 2 RCC 3
RCC 4 RCC 5
P-value = 0.002
*
*
* Protocol Deviation
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IN.PACT Global Study: Standard vs. Broader UseBaseline Lesion Characteristics
IN.PACT Global Standard Use DCB
N= 281 SubjectsN= 281 Lesions
IN.PACT Global Broader Use DCB
N= 1125 SubjectsN= 1492 Lesions
P-value
Lesion Type: % (n)De novo
Restenotic (non-stented)In-stent Restenosis
92.5% (260/281)7.5% (21/281)0.0% (0/281)
70.8% (1057/1492)7.7% (115/1492)
21.4% (320/1492)< 0.001
Lesion Length (cm ± SD)Range (Min, Max cm)
7.86 ± 4.531.0 – 18.0
12.88 ± 10.010.5 – 54.0
< 0.001
Total Occlusions % (n) 34.2% (96/281) 35.7% (533/1492) 0.635
Calcification % (n)Severe1 % (n)
54.8% (154/281)0.0% (0/281)
71.3% (1063/1490)12.1% (181/1490)
< 0.001
RVD (mm ± SD) 5.157 ± 0.656 5.191 ± 0.686 0.440
Diameter Stenosis (% ± SD) 89.1 ± 11.2 88.7 ± 12.5 0.590
Dissections:none
A-CD-F
49.1% (138/281)41.6% (117/281)
9.3% (26/281)
58.2% (868/1491)34.2% (510/1491)7.6% (113/1491)
0.035
111. Severe calcium definition used by study sites and core laboratory is bilateral calcium at the same location (also measured in sections), ≥ half of the total lesion length,
≥180◦ (both sides of the vessel at the same location). Dattilo, R; J Invasive Cardiol 2014;26(8):355360
IN.PACT Global Study: Standard vs. Broader UseProcedural Characteristics
IN.PACT Global Standard Use DCB
N= 281 SubjectsN= 281 Lesions
IN.PACT Global Broader Use DCB
N= 1125 SubjectsN= 1492 Lesions
P-value
Device Success1 % (n) 100.0% (353/353) 99.3% (2631/2649) 0.257
Procedure Success2 % (n) 100.0% (279/279) 99.1% (1107/1117) 0.227
Clinical Success3 % (n) 99.6% (278/279) 98.6% (1101/1117) 0.221
Guidewire ApproachTrue lumenSub-intimal
91.8% (258/281)8.2% (23/281)
85.7% (1279/1492)14.3% (213/1492)
0.005
Pre-dilatation % (n)Post-dilatation % (n)
69.4% (195/281)30.0% (84/280)
80.2% (902/1125)36.4% (407/1117)
< 0.0010.050
Provisional Stent % (n) 16.1% (45/280) 27.6% (308/1117) < 0.001
1. Device success defined as successful delivery, inflation, deflation and retrieval of the intact study balloon device without burst below the RBP.2. Procedure success defined as residual stenosis of ≤ 50% (non-stented subjects) or ≤ 30% (stented subjects) by core lab (if core lab was not available then the site-reported
estimate was used). 3. Clinical success defined as procedural success without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or TVR) prior to
discharge.
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IN.PACT Global Study: Standard vs. Broader UseFreedom From CD-TLR Through 3 Years
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IN.PACT Global Study: Standard vs. Broader UseAdditional 3-Year Effectiveness Outcomes
36 month outcomes Standard Use DCBN= 281 Subjects
Broader Use DCBN= 1125 Subjects
P-value
Clinically – Driven TLR1 14.7% (37/251) 25.7% (252/979) < 0.001
Any TLR2 15.1% (38/251) 26.3% (257/979) < 0.001
Time to first CD-TLR (days) 541.4 ± 267.2 465.8 ± 288.5 0.134
1. Any re-intervention within the target lesion(s) due to symptoms or drop of ABI of ≥ 20% or > 0.15 when compared to post-index procedure baseline ABI. Any TLR includes clinically-driven and incidental or duplex driven TLR
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IN.PACT Global Study: Standard vs. Broader UseSafety Outcomes Through 3 Years
36 month outcomesIN.PACT Global Standard Use
N= 281 Subjects
IN.PACT Global Broader Use
N= 1125 SubjectsP-value
Primary Safety Endpoint 1 83.3% (209/251) 72.9% (714/979) < 0.001
Major Adverse Events 2 24.3% (61/251) 34.8% (341/979) 0.002
Death (all-cause) 7.2% (18/251) 8.6% (84/979) 0.523
Major Target Limb Amputation
0.0% (0/251) 1.0% (10/979) 0.228
Thrombosis 3.6% (9/251) 6.3% (62/979) 0.128
1. Composite of 30-day freedom from device- and procedure-related mortality and freedom from major target limb amputation and clinically-driven TVR within 36 months.2. Major Adverse Events: Composite of death, major target limb amputation, clinically-driven TVR, and thrombosis.
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Outcomes Across IN.PACT Clinical StudiesThrough 3 Years
IN.PACT SFA3 Yr1
(DCB ARM)(N=220)
IN.PACT Japan3 Yr2
(DCB ARM)(N=68)
IN.PACT Global 3 Yr
Standard Use (N= 281)
IN.PACT GlobalClinical Cohort
3 Yr3
(N=1406)
IN.PACT Global 3 Yr
Broader Use (N= 1125)
Lesion Length (Mean ± SD, cm)
8.94 ± 4.89 9.15 ± 5.85 7.86 ± 4.53 12.09 ± 9.54 12.88 ± 10.01
In-stent Restenosis (ISR) %
0.0% -- 0.0% 18.0% 21.4%
Chronic Total Occlusion (CTO) %
25.8% 16.2% 34.2% 35.5% 35.7%
CD-TLR 15.2% 14.9% 14.7% 23.5% 25.7%
Thrombosis 2.0% 1.4% 3.6% 5.8% 6.3%
Major Amputation Target Limb
0.0% 0.0% 0.0% 0.8% 1.0%
All –Cause Death 10.7% 6.0% 7.2% 8.3% 8.6%
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1. Schneider P. et al. Circ-CI. 2017
2. Iida O. as presented LINC Leipzig 2019
3. Tepe G. as presented CIRSE Lisbon 2018
IN.PACT Global Study: Standard vs. Broader UseSummary
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• The IN.PACT Global Study remains the largest, adjudicated, real-world DCB study reporting 3-year outcomes in complex femoropopliteal lesions
• This analysis comparing standard IN.PACT Admiral DCB use to a broader IN.PACT Admiral DCB use in complex lesions demonstrates durable and consistent performance through 3 years
– Standard DCB use outcomes are consistent with other 3-year outcomes from IN.PACT IDE-like trials (IN.PACT SFA, IN.PACT Japan)
– Broader DCB use outcomes are consistent with the IN.PACT Global Study results
Insights from the IN.PACT Global Study 3-year Data: Does Lesion
Complexity Affect Results?
Jos van den Berg, MD
Ospedale Civico Lugano
Lugano, Switzerland
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