LIBERTY 360 Study: Procedural and 30-day Outcomes of Endovascular
Interventions in Patients with Symptomatic Lower Extremity Peripheral
Arterial Disease
Jihad A. Mustapha, MD, FACC, FSCAIMetro Health Hospital
Wyoming, MI
On behalf of the LIBERTY Investigators
Disclosures
Consultant to:
• Abbott Vascular
• Bard Peripheral Vascular
• Boston Scientific
• Cardiovascular Systems, Inc.
• Cook Medical
• Medtronic
• Spectranetics
• Terumo
PAD and CLI
1. Fowkes FG, et al. Lancet. 2013;382:1329-1340.
2. Hankey GJ, et al. JAMA. 2006;295:547-553.
3. Eggers PW, et al. Kidney Int. 1999;56:1524–1533.
4. Abu Dabrh AM, et al. J Vasc Surg. 2015;62:1642–1651.e3.
5. Allie DE, et al. EuroIntervention. 2005;1:75–84.
6. Henry AJ, et al. J Vasc Surg. 2011;53:330–339.e1.
7. Abou-Zamzam AM, et al. Ann Vasc Surg. 2007;21:458–463.
8. Baser O, et al. Vasc Dis Manag. 2013;10:E26–E36.
9. Goodney PP, et al. Circ Cardiovasc Qual Outcomes 2012;5:94–102.
10. Jindeel A & Narahara KA. Int J Low Extrem Wounds. 2012;11:177–179.
11. Dillingham TR, et al. Arch Phys Med Rehabil. 2005;86:480–486.
12. Pasquina PF, et al. Curr Phys Med Rehabil Rep. 2014;2:273–289.
13. Schofield CJ, et al. Diabetes Care. 2006;29:2252–2256.
14. Tentolouris N, et al. Diabetes Care. 2004;27:1598–1604.
15. Faglia E, et al. Eur J Vasc. Endovasc Surg. 2006;32:484–490.
Mustapha et al., LIBERTY 360° Study Presentation at AMP 2016 Reveals Hope for Rutherford-6 CLI Patients
Cath Lab Digest. Volume 24 - Issue 10 - October 2016
>200 million people have PAD worldwide1
27 million persons suffer from CLI in North America and Europe2
CLI is highly prevalent in older patients with DM and/or ESRD3, and is associated with high risk of amputation and mortality4
Primary amputation continues to be first-line therapy in up to 67% of CLI patients4-8
73%6 had no diagnostic angiogram and 54%9 received no vascular procedure prior to the amputation
The results following the primary amputation can be devastating
27% of the patients will have one or more re-amputation(s) within 1 year10
35% will have a higher level of limb loss11
55% will get the other limb amputated within 2-3 years12
The mortality rates after primary amputation are very high 1-year mortality rates ranging from 9% to 33%10,11,13,14
5-year mortality rates ranging from 26% to 82%10,13–15
LIBERTY 360° Study• LIBERTY is a prospective, observational, multi-center study to evaluate
procedural and long-term clinical and economic outcomes of endovascular device interventions in patients with symptomatic lower extremity PAD
• The LIBERTY study includes any FDA-approved technologies to treat claudication and CLI
• 4 core laboratories were utilized for independent analysis
• 1,204 subjects were enrolled at 51 sites and will be followed up to 5 years
• Endpoints include: Procedural and lesion success, Major Adverse Events (MAEs), Duplex ultrasound, Quality of life (QoL), Six-minute walk test (6MWT), Economic analysis
Adams et al. Am Heart J. 2012; 2016;174:14-21.
ClinicalTrials.gov NCT01855412
LIBERTY Enrollment and 30-day Follow-up
1,204 Subjects Enrolled at 51 sites
All Comers / All Treatments
Rutherford 2-3500 Subjects*
Rutherford 4-5589 Subjects*
Rutherford 6100 Subjects
3.0% withdrawal/lost to follow-up
2.4% missed 30-day visit
5.5% withdrawal/lost to follow-up
5.8% missed 30-day visit
7.0% withdrawal/lost to follow-up
10.0% missed 30-day visit
Rutherford 2-3474 Subjects
Rutherford 4-5535 Subjects
Rutherford 683 Subjects
30-day Follow-up
*Due to site closure and lack of PI signature, baseline & procedure data from 15 subjects were excluded.
Rutherford 2, N=97; Rutherford 3, N=403; Rutherford 4, N=285; Rutherford 5, N=304
Core Lab reported lesions.
595 Lesions 744 Lesions 146 Lesions
LIBERTY Device Usage by LesionBalloon and/or atherectomy were preferred devices
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Balloon Atherectomy Stent Bailout stent*
Rutherford 2-3 (N=595)
Rutherford 4-5 (N=744)
Rutherford 6 (N=146)
*Bailout stent group is a subset of Stent group
Core Lab reported lesions.
Lesions with reported values may be less than total number of lesions treated in each arm.
Comparison between Rutherford
categories significant (p<0.05)
29.5%33.7% 34.8%
Mean final post-procedure percent stenosis
80.6%83.6%
80.5%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Mean pre-procedure percent stenosis
LIBERTY Target Lesion Percent StenosisHigh mean pre-procedure stenosis across all Rutherford Classes and approximately 30% final percent stenosis post-PVI across all
groups
Core Lab reported lesions.
Lesions with reported values may be less than total number of lesions treated in each arm.
Comparison between Rutherford
categories significant (p<0.05)
Rutherford 2-3 (N=595)
Rutherford 4-5 (N=744)
Rutherford 6 (N=146)
Core Lab Reported Lesions.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Worsened No Change Improved
Difference post-treatment vs. pre-treatment
Rutherford 2-3 Rutherford 4-5 Rutherford 6
LIBERTY Runoff VesselsNumber of runoff vessels increased post-PVI with significant improvement seen in RC4-5 and RC6 compared to RC2-3,
showing the utility of PVI for even the most difficult patients.
0%
10%
20%
30%
40%
50%
3 2 1 0
# patent runoff vessels pre-treatment
0%
10%
20%
30%
40%
50%
3 2 1 0
# patent runoff vessels post-treatment
Comparison between Rutherford
categories significant (p<0.05)
Procedural Success EndpointIn RC6 group, <50% residual stenosis in 77.7% of the subjects, and no angiographic complications in 86.7% of subjects.
84
.5%
77
.5%
70
.5%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Procedural Success(<50% RS)
90
.8%
92
.9%
84
.2% 90
.1%
77
.7% 8
6.7
%
Final Percent Stenosis <50% No Severe AngiographicComplications
Core Lab reported lesions. Severe angiographic complications include: Perforation, Dissection C-F, Distal Embolization, and Acute Vessel ClosureP-Values from Fisher’s Exact Test.
Comparison between Rutherford
categories significant (p<0.05)
Rutherford 2-3 (N=478)
Rutherford 4-5 (N=550)
Rutherford 6 (N=95)
Duplex Ultrasound (DUS): 30-daysHigh patency rate in RC2-3 subjects
• Core Lab Analyzed (VasCore)
• Collected only for Rutherford 2-3 Subjects
95.5% (n=336/352) of the RC2-3 subjects
had a Target Lesion Peak Systolic
Velocity Ratio (PSVR) ≤ 2.4
90% 95% 100%
30-Day Freedom from MAE ComponentsHigh freedom from TVR was reported across all Rutherford Classes (99.4% in R2-3, 96.9% in R4-5, and 97.9% in R6).
More than 95% of the RC6 subjects were free from death and major amputation at 30-days, respectively. PVI may be the considered as the primary option for RC6 patients, not primary amputation.
90% 95% 100% 90% 95% 100%
Death Major Amputation TVR
95.9%
99.7%
99.6%
95.8%
98.8%
100.0%
97.9%
96.9%
99.4%
Kaplan-Meier method used to obtain estimate of freedom from MAE.
Greenwood’s method used to obtain the 95% confidence interval for the estimate.
(Point Estimate and 95% Confidence Intervals)
RC 2-3 RC 4-5 RC 6
At risk 475 566 91
Events 2 2 4
Censored 22 21 4
RC 2-3 RC 4-5 RC 6
At risk 473 548 89
Events 3 18 2
Censored 23 23 8
RC 2-3 RC 4-5 RC 6
At risk 475 560 88
Events 0 7 4
Censored 24 22 7
RC 2-3
RC 4-5
RC 6
Rutherford 2-3 (N=500) Rutherford 4-5 (N=589) Rutherford 6 (N=100)
Discharged to home
Rutherford 2-3 Rutherford 4-5 Rutherford 6
LIBERTY Discharge SummaryProcedural complications rarely (0.8%-2.0%) resulted in post-procedural hospitalization in all Rutherford Classes and
78% of RC6 subjects were discharged to home.
0%
20%
40%
60%
80%
100%
Rutherford 2-3 Rutherford 4-5 Rutherford 6
with additional therapy due to complications
Hospitalization post index procedure Discharged to home
Patients with reported values may be less than total number of patients enrolled in each arm.
Comparison between Rutherford
categories significant (p<0.05)
Quality of Life: VascuQoLQuality of life improved from baseline at 30-days across all Rutherford Classes
Vascular Quality of Life Questionnaire; a PAD-specific health-related quality of life instrument
Higher subdomain scores indicate better rating of health.
Activity subdomain: Significance noted (p<0.05) in change from baseline in 2-3 vs. 4-5.
Pain subdomain: Significance noted (p<0.05) in change from baseline in 2-3 vs. 6.
1234567
Baseline 30-Day
SocialSubdomain Score
1234567
Baseline 30-Day
Physical Activity Subdomain Score
1234567
Baseline 30-Day
PainSubdomain Score
1234567
Baseline 30-Day
EmotionalSubdomain Score
1234567
Baseline 30-Day
SymptomSubdomain Score
1234567
Baseline 30-Day
TotalScore
67%
35%
43%
24%
33%
22%
21%
4.2%
0% 10% 20% 30% 40% 50% 60% 70% 80%
Allie et al., 2005
Hynes et al., 2005
Abou-Zamzam et al., 2007
Henry et al., 2011
Baser et al., 2013
Abu et al., 2015
Reinecke et al., 2015
Liberty 360
Primary Amputation as a First Line of Treatment CLI Patients without Endovascular Treatment vs. LIBERTY 360° R6 CLI Patients
1. Abou-Zamzam AM, et al. Ann Vasc Surg. 2007;21:458–463.
2. Abu Dabrh AM, et al. J Vasc Surg. 2015;62:1642–1651.e3.
3. Allie DE, et al. EuroIntervention. 2005;1:75–84.
4. Baser O, et al. Vasc Dis Manag. 2013;10:E26–E36.
5. Henry AJ, et al. J Vasc Surg. 2011;53:330–339.e1.
6. Hynes N, et al. Eur J Vasc Endovasc Surg. 2005;30:291-299.
7. Reinecke H, et al. Eur Heart J. 2015;36:932-938.
Mustapha et al., LIBERTY 360° Study Presentation at AMP 2016 Reveals Hope for Rutherford-6 CLI Patients
Cath Lab Digest. Volume 24 - Issue 10 - October 2016
30-day
This summary graph shows the primary amputation
rates presented in the literature, but it is not a head-to-
head comparison since the analyses described vary in
design/method/etc.
• High freedom from 30-Day Major Adverse Events (MAE: TVR, death, and major amputation) seen across all Rutherford Classes.
• Procedural complications rarely (0.8%-2.0%) resulted in post-procedural hospitalization in all Rutherford Classes and 78% of RC6 subjects were discharged to home.
• The LIBERTY 360 clinical data through 30 days demonstrated that on average PAD patients (Rutherford Class 2-6) post-PVI had favorable outcomes and improved quality of life.
• The early findings in this novel all-comers PAD study suggest that “watchful waiting” in RC2-3 and “primary amputation” in RC6 may not be necessary—PVI can be successful in this patient population as well.
Conclusions
LIBERTY 360 Study: Procedural and 30-day Outcomes of Endovascular Interventions in Patients with
Symptomatic Lower Extremity Peripheral Arterial Disease
Jihad A. Mustapha, MD, FACC, FSCAIMetro Health Hospital
Wyoming, MI
On behalf of the LIBERTY Investigators
