Outcomes of CLI RCTs and Registries: Key Take-Home Points · Bypass vs. Angioplasty in Severe Ischemia of the Leg (BASIL) Conclusion A bypass-surgery-first and a balloon-angioplasty-first
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Olive registry: 3-years outcome of BTK intervention in Japan
Osamu Iida, MD
Kansai Rosai Hospital
Amagasaki, Hyogo, Japan
What is the optimal treatment for the patient with critical limb ischemia (CLI)?
Recommendation 24. Optimal treatment for patients with CLI Revascularization is the optimal treatment for patients with CLI.
Transmetatarsal Amputation
Medical intervention for CLI patients who were not
candidates for revascularization (Learn from Circulase trial)
Brass EP, et al. J Vasc Surg. 2006;43:752-9.
Conclusion
Intensive treatment with lipo-ecraprost failed to modify the 6-month
amputation rate in patients with CLI who were not candidates for revascularization.
Days from the first dose
0 20 40 60 80 100 120 140 160 180 200 % o
f p
atie
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wit
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50
60
70
80
90
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Placebo
Lipo-ecraprost
Log-rank test p = 0.308
Event Placebo
(n =177) (%) Lipo-ecraprost (n = 179) (%)
P value
Major amputation 23 (13.0) 29 (16.2) N.S Death 10 (5.6) 18 (10.1) N.S
Composite (amputation or death) 31 (17.5) 43 (24.0) N.S
Pain free at 6 months 44 (24.3%) 40 (22.1%) N.S
Ulcer free at 6 months 25 (24.5%) 25 (23.2%) N.S
Bypass therapy (BSX) Endovascular therapy (EVT)
Revascularization for patients with critical limb ischemia
Amputation-free survival All-cause mortality
Surgery vs. Endovascular Therapy (EVT) Bypass vs. Angioplasty in Severe Ischemia of the Leg (BASIL)
Conclusion A bypass-surgery-first and a balloon-angioplasty-first strategy are associated with
broadly similar outcomes in terms of amputation-free survival, and in the short-term, surgery is more expensive than angioplasty.
Adam DJ, et al. Lancet. 2005;36:1925-34.
AFS (amputation-free survival) for patients undergoing bypass therapy (SVG vs. PTFE) and angioplasty (Sub vs. Intra)
AFS: Bypass (SVG) > Angioplasty (Sub=Intra)> Bypass (PTFE)
Analysis of AFS and Overall Survival by Treatment Received Bypass vs. Angioplasty in Severe Ischemia of the Leg (BASIL)
Bradbury AW, et al. J Vasc Surg 2010;51:18S-31S.
Results of BSX after failed BAP. The 37 patients who underwent BSX after first attempted failed angioplasty had poorer AFS (P=0.006, log-rank test) and somewhat poorer OS (P=0.06, log-rank test) than the 184 patients who underwent BSX as first treatment.
Analysis of AFS and Overall Survival by Treatment Received Bypass vs. Angioplasty in Severe Ischemia of the Leg (BASIL)
Amputation-free survival Overall survival
Bradbury AW, et al. J Vasc Surg 2010;51:18S-31S.
Life expectancy of >2 years with a usable autogenous vein
⇒ Bypass therapy first
Life expectancy of <2 years without an adequate vein
⇒ Endovascular therapy first
The predictors of 2-year mortality for patients with CLI have not been examined well.
Decision making for CLI treatment based on current AHA guidelines
Andrew WB, et al. J Vasc Surg. 2010;51:18S-31S.
Anderson JL, et al. Circulation. 2013;127:1425-43.
Factors Univariate analysis Multivariate analysis
Hazard ratio [95%CI] P-value Hazard ratio[95%CI] P-value
Age >75 1.63 [1.06-2.51] *0.024 1.74 [1.11-2.74] *0.015
Male 1.01 [0.64-1.58] 0.955 0.91 [0.57-1.44] 0.705
Rutherford classification
1.67 [1.15-2.43] *0.007 1.26 [0.84-1.90] 0.255
Nonambulatory status
7.08 [4.03-12.4] *<0.001 5.34 [3.01-9.46] *<0.001
BMI <18.5 2.04 [1.31-3.20] *0.001 1.41 [0.88-2.25] 0.145
Regular dialysis 2.58 [1.63-4.08] *<0.001 2.11 [1.28-3.49] *0.003
Ejection fraction <50 %
3.25 [2.05-5.15] *<0.001 2.23 [1.37-3.62] *0.001
CI, Confidence interval; BMI, Body mass index *: P <0.05
Predictive scoring model of mortality after surgical or endovascular revascularization in patients with CLI: multivariate analysis for 2-year mortality
Shiraki T, Iida O, et al. J Vasc Surg. 2014;60:383-9.
≥2 risks
≥1 risk
≥3 risks
≥4 risks AUC = 0.81
(95% CI: 0.76 – 0.86)
SCORE for critical limb ischemia
POINTS
Age >75 1
Nonambulatory status 1
Regular dialysis 1
LVEF <50% 1
LVEF: Left ventricular ejection fraction AUC: Area under the curve
Predictive scoring model of mortality after surgical or endovascular revascularization in patients with CLI: receiver operating characteristic curve
Shiraki T, Iida O, et al. J Vasc Surg. 2014;60:383-9.
AFS were 86±2%, 81±2%, 77±3%, and 74±3% at 3, 6, 9, and 12
months, respectively.
OLIVE (endOvascuLar treatment for Infrapopliteal Vessel):
1-year results
Variables HR (95%CI) P value
BMI <18.5 2.22(1.23-4.01) 0.008
Statin administration 0.59(0.30-1.13) 0.11
Anemia 1.80(0.97-3.32) 0.06
Heat failure 1.73(1.02-2.91) 0.04
Wound infection 1.89(1.07-3.32) 0.02
Primary Endpoint: Amputation-free survival
Iida O, et al. Circ Cardiovasc Interv. 2013;6:68-76.
Independent predictors for AFS
BMI <18.5 Wound infection Heat failure
75% Rutherford 5 25% Rutherford 6
Secondary Endpoint: Time to wound healing
The proportion of not-healed patients was 54±3%, 29±3%, 18±3%, and 14±3% at 3, 6, 9, and
12 months, respectively.
Median value was 97±10 days.
OLIVE (endOvascuLar treatment for Infrapopliteal Vessel):
1-year results
Variables HR (95%CI) P value
BMI <18.5 0.54(0.31-0.96) 0.03
Hemodialysis 0.79(0.58-1.09) 0.15
Wound infection 0.60(0.36-0.98) 0.04
Independent predictors for Time to wound healing
Iida O, et al. Circ Cardiovasc Interv. 2013;6:68-76.
BMI <18.5 Wound infection
0
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0 12 24 36
Am
pu
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-fre
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urv
ival
(%
)
Follow-up period (months)
0 12 24 36
No. at risk 312 204 165 94
Rate (%) 100 73.6 64.2 55.2
Factors
OLIVE (endOvascuLar treatment for Infrapopliteal Vessel):
1-year and 3-year results
Primary Endpoint: Amputation-free survival
BMI <18.5 Wound infection Heat failure BMI <18.5 Age Chronic Dialysis Rutherford 6
Risk factors for amputation-free survival in patients with critical limb ischemia
in short period
in short and long period
BMI <18.5 Wound infection Heat failure
BMI <18.5 Age Chronic Dialysis Rutherford 6
Stepwise analysis for recurrence of wound OR 95%CI Wald
Lower Upper p-value
ALL
Male Gender 1.61 0.74 3.52 0.23
Serum albumin<3.0g.dL 2.72 0.42 17.61 0.29
Diabetes mellitus 1.75 0.76 4.01 0.19
Hemodialysis 1.52 0.74 3.14 0.26
Isolated below-the knee lesions 4.54 2.20 9.37 <.0001
STEPWISE
Diabetes mellitus 2.05 0.94 4.45 0.07
Isolated below-the knee lesions 4.28 2.15 8.53 < 0.001
Recurrence of wound until 3 years: 43.9 %
OLIVE (endOvascuLar treatment for Infrapopliteal Vessel):
3-year results
Secondary Endpoint: Wound recurrence and its predictors
18,7%
28,5%
37,0%
7,6%
7,3%
7,8%
14,7%
9,4%
5,6%
58,9%
54,8%
49,6%
0% 20% 40% 60% 80% 100%
EVT after 1 year
EVT after 2 years
EVT after 3 years
Death Major amputation
Survive with wounds Survive without wounds
OLIVE (endOvascuLar treatment for Infrapopliteal Vessel):
3-year results
Secondary Endpoint: Time to wound healing
WIFI Classification System: Risk Stratification Based on Wound, Ischemia, and Foot Infection
Wound: extent and depth
Ischemia: perfusion/flow
Foot Infection: presence and extent
Based on existing validated systems or best available data with 4 point scales where:
0 = none, 1 = mild-moderate, 2 = moderate-severe, 3 = severe or advanced
Estimate risk of amputation at 1 year for each combination
Very low = VL , Low = L, Moderate = M, High = H
Mills JL Sr, et al. J Vasc Surg. 2014;59:220-34.
Representative case of CLI with concurrent R6 and wound infection
Case: 65 yrs, Male, Ambulatory status Risk factor: DM, hemodialysis Labo data: Alb 2.6 g/dL, CRP 37.4 mg/dL
Endovascular Therapy (EVT) Distal puncture and subintimal angioplasty
Proximal Distal
Final angiogram
Emergent debridement and minor amputation
Time course of wound healing
5 months Re-EVT: 3 times
Secondary infection due to limb wound infection during healing process
1 months late Post-sternotomy osteomyelitis ⇒Sternal resection and wire exclusion
5 months later Pacemaker lead infection
Differential impact of WIfI classification on wound healing rate after EVT for CLI with and without malnutrition status
WIfI classification was clinically useful in predicting wound healing rate after endovascular therapy. Differential impact of WIfI classification on wound healing rate after EVT for CLI with and without malnutrition status was observed.
3-Month Outcomes in J-BEAT Angio Registry
Iida O, et al. Eur J Vasc Endovasc Surg. 2012;44:425-31.
5%
32%
40%
73%
13% 15%
48%
82%
0%
20%
40%
60%
80%
100%
Mortality Without complete healingor recurrence of rest pain
Reintervention Restenosis per lesion
3 months 12 months
BTK lesion
1-year results from the ACHILLES trial: Comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease
Scheinert D, et al. J Am Coll Cardiol. 2012;60:2290-5.
Study design: Multicenter, randomized trial
Study subjects: SES (n=99) vs angioplasty (n=101)
Lesion length: 27±21mm vs 27±21mm
Stent: CYPHER SELECT stents (J&J)
Primary endpoint: Angiographic binary restenosis
Outcomes: Restenosis rate: 22% vs 42%
Freedom from death, TLR, bypass
amputation, and R≥4: 70% vs 50% Cypher stent
Angioplasty
VS.
SES implantation may offer a promising therapeutic alternative to PTA for treatment of infrapopliteal peripheral arterial disease.
Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): A randomized trial in diabetic patients with critical limb ischemia
Liistro F, et al. Circulation. 2013;128:615-21.
12m
* Time to wound healing 4.4±1.5 vs 5.2±1.6 months
Device: IN.PACT Amphirion, Medtronic
Average lesion length: 129±83mm (DCB) vs 131±79mm (PTA)
DEB compared with PTA strikingly reduces 1-year restenosis, target lesion revascularization, and target vessel occlusion in the treatment of BTK lesions in diabetic patients with CLI.
Prospective, multicenter, RCT, Independent, angiographic and wound core lab
358 patients randomized 2:1 DEB:PTA (lesion length: 10.2±9.1 vs. 12.9±9.5 cm)
Randomized trial of IN.PACT Amphirion DEB vs. PTA for infrapopliteal revascularization in CLI: 12-month results
Zeller T, et al. J Am Coll Cardiol. 2014;64:1568-76.
Primary Efficacy DEB PTA p
12-month LLL (mm) 0.61 ± 0.78 0.62 ± 0.78 0.95
12-month CD-TLR 9.2% (18/196) 13.1% (14/107) 0.291
Primary Safety DEB PTA p
6-month death, major amputation or CD-TLR
17.7% (41/232)
15.8% (18/114)
0.021 (noninferiority) 0.662 (superiority)
IN.PACT DEEP did not meet either 1⁰ efficacy endpoint.
IN.PACT DEEP Trial met the noninferiority primary safety endpoint.
Primary Outcomes
Take-Home Messages
Revascularization is the optimal treatment for patients with CLI.
BASIL finally concluded that beyond 2 years after revascularization there appeared to be a benefit for open bypass therapy (BSX).
Long-term clinical outcomes were acceptable after EVT for patients with CLI due to infrainguinal lesions.
DEBATE-BTK shows that DEB compared with PTA strikingly reduces 1-year restenosis in the treatment of BTK lesions in diabetic patients with CLI, whereas IN.PACT DEEP did not meet 1⁰ efficacy endpoint.
Olive registry: 3-years outcome of BTK intervention in Japan
Osamu Iida, MD
Kansai Rosai Hospital
Amagasaki, Hyogo, Japan
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