Drug-Eluting Stents vs PTA for

Tibial Occlusive Disease

Khalil Qato PGY-2
Vascular Surgery Resident
Lenox Hill Hospital
 The case for Drug-Eluting Stents
• Background/Review of Pertinent Literature

• By end of presentation:
– Better patency (short and long term)
– Better Limb salvage
 Background – Critical Limb Ischemia
Incidence of CLI from 500-1,000/million per year, subset of PAD

Pathophysiology: Blood flow insufficient to meet tissue metabolic

demand

Risk Factors: DM, HTN, HLD, Smoking, ESRD

Clinical Presentation:
• Intractable foot, ankle or leg pain at rest
• Non-healing ischemic ulcerations or necrotic tissue

Up to 40% of patients will require limb amputation

Annual mortality exceeds 20%
Anatomy
Classification
 Treatment Options
1. Surgical Bypass
Ant. Tibial a.
2. Atherectomy
Post. 3. Percutaneous transluminal angioplasty
Tibial a (PTA) *
Peroneal a. 1. Laser/Cutting/Drug-
eluting/Cryoplasty

4. Stent (BMS/DES)*

5. Angioplasty + stent
 Treatment of Infrapopliteal Vessels -
Challenges
• Small Vessel Size

• Prevalence of diffuse calcific disease

• Fewer suitable target vessels for bypass

• Higher risk of restenosis, thrombosis and

amputation
 Why Endovascular over bypass?
• Decreased periop M & M

• Lack of proper vein conduit

• Increasing technical expertise and

advancements in technology
 Treatment Goals
• Improve patency rate (freedom from
restenosis >50%)

• Clinical Goals:
– Wound healing (need in-line flow)
– Prevent further ulceration
– Eliminate rest pain
 Current Treatment Guidelines
• Primary Angioplasty as Standard of Care
– Acceptable clinical outcome at a low procedural
cost
• Bail-out stenting in cases of sub-optimal
angioplasty or flow-limiting dissection
PTA Patency

Limb Salvage

Secondary
Patency

>50% Restenosis at
Primary Patency 1 yrs

Ramiti et al 1998
• 77 infrapopliteal lesions >80mm in length
• Treated with 80-120mm balloons
• Rutherford 4/5 pts.
• 3 months: 68.8% restenosis or reocclusion
– Clinical: 75.8% showed improved healing
• Conclusion: restenosis rate after PTA of extensive infrapopliteal
angioplasty is high and occurs early after treatment
 Stents
• Bare Metal or Drug-eluting
Drug-eluting: worked in coronaries…
• Contained within a slow-release polymer
• Sirolimus
– DNA arrest within SMC preventing SMC proliferation
– Inhibits collagen synthesis, SMC migration, and
inflammation
• Paclitaxel:
– Inhibits microtubule disassembly, arresting the cell
cycle in mitosis and prevents SMC proliferation
Stents and Restenosis
 Questions
• Do Drug-eluting stents work in tibial vessels?

• Are they safe?

• Are they better than standard of care (PTA)?

 DESTINY Trial – DES vs BMS:
Bosiers et al JVS 2012
• Industry-initiated Randomized Trial - Everolimus stent vs BMS
• 140 pts with CLI (Rutherford Category 4-5)
– 74 pts DES
– 66 pts BMS
• Max 2 focal lesions in 1 or more infrapopliteal a.
• Results
– Primary Patency (absence of >50% restenosis) at 12 mos
• DES 85.2%
• BMS 54% (p<0.0001)
– Target lesion revascularization
• DES – 8.7%
• BMS – 33.6%
– No Difference in limb salvage/pain relief
 YUKON – BTX:
Rastan et al JACC 2012
Randomised Double Blind • Limb Salvage (p>0.05)
– 82 pts: SES – SES: 98.7%
– 79 pts: BMS – BMS: 94.6%
• Mean lesion length: 31mm • Target Vessel Revascularization
(P>0.05)
3 year Results: – SES: 9.2%
– BMS: 20%
• Event Free Survival (p=.02)
– SES: 65.8%
• Rutherford Class Improvement:
(p=0.006)
– BMS: 44.6%
– SES: -2
• Primary Patency 1 yr: p<0 – BMS: -1
– SES: 81%
– BMS: 56%
• Target Limb Amputation (p=.03)
– SES: 97.4%
– BMS: 87.8%
 PaRADISE – Preventing Amputations
Using Drug-eluting Stents
• Non-randomised trial
• Cohort of 106 pts treated with 228 DES
• Primary endpoints: limb salvage, amputation,
major adverse events after 3 yrs f/u
– Amputation – 6% at 3 yrs
– 99% of non-amputated limbs had resolution of sx
– 93% with wound healing and relief of rest pain
– Target limb revascularization: 15%
– Binary Restenosis: 12%
 Questions
• Do Drug-eluting stents work in tibial vessels?
YES

• Are they safe? YES

• Are they better than standard of care (PTA)?

– ???
DES vs PTA
 Karnabatidis et al – DES vs PTA/BMS
• Prospective Study
• 2 Arms
– Primary drug eluting stent (Evorolimus)
– Primary PTA with BMS bailout stent
• 81 pts total
– DES: 47 pts, 51 CLI Limbs, 102 lesions
– PTA/BMS: 34 pts, 36 CLI Limbs, 72 lesions
 Karnabatidis et al – DES vs PTA/BMS
• Baseline demographics well-matched
• Median Rutherford classification
– DES: 4
– PTA/BMS: 5
• Avg total lesion length: 7.6cm BOTH
• Avg stented lesion length:
– DES: 7.7cm
– PTA/BMS: 4.2cm
Karnabatidis et al – DES vs PTA/BMS
 Karnabatidis Endpoints

DES DES
DES

PTA
PTA PTA

Better Patency
Better Survival
Better Limb Salvage
 Achilles Trial
• Design: prospective, randomized, multi-center
• Primary endpoint: in-segment binary
restenosis
• Secondary endpoints: technical success rates,
TLR, TVR, death, amputation, Rutherford
status, stent fracture, wound status
• F/U: 6 wks, 6 months, 12 months
• Sponsor: Cordis, Johnson & Johnson
 ACHILLES: Inclusion Criteria
• Symptomatic CLI (Rutherford 3-5)

• Target vessel diameter >2.5 and <3.5mm

• Target lesion stenosis >70%

• Max lesion length 120 mm

• Max 4 stents within 1 vessel

 ACHILLES Trial
• 200 pts
• Randomized to:
– SES (n=99 pts, 113 lesions)
– PTA (n=101 pts, 115 lesions)
• Average Lesion length: 26.9mm
– 81.3% of stented pts had 1 total occlusion
– 15% highly calcified lesions
ACHILLES - Demographics
ACHILLES - Results
ACHILLES – Clinical Endpoints
 ACHILLES – Clinical Endpoints
• Mean baseline Rutherford Class 4.1 (DES) vs
4.0 (PTA)
– At 1 yr: 76% of DES had improvement in
Rutherford category
• 67% of PTA (P=0.23)
 ACHILLES - Conclusions
• Better Primary Patency, especially in Diabetics

• Higher device-, lesion-, procedure based

success rates for stent arm

• Trend towards better clinical outcome

DES vs DEB
-- Rutherford 3-6, minimum lesion length 70mm
-- 50 pts DEB or Primary DES placement
• Post procedure stenosis: p<0.0001
– DES: 9.6%; DEB: 24.8%
• Restenosis: p=0.04
– DES: 28%; DEB 57.9%
• TLR: p =0.65
– DES: 7.7%; DEB: 13.6%
 Questions
• Do Drug-eluting stents work in tibial vessels?
YES

• Are they safe? YES

• Are they better than standard of care (PTA)?

– Better patency, Better Survival, Better Limb
Salvage