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In-Stent Restenosis: The Tail IS Wagging the Dog

Michael S. Conte MDDivision of Vascular and Endovascular Surgery

UCSF Heart and Vascular CenterUCSF Vascular Symposium 2016

Disclosures

•NONE

IF YOU WERE A PAD PATIENT:What is the minimum efficacy threshold you would accept for an invasive treatment strategy for life-style limiting claudication?

1. >50% likelihood of improvement for at least one year

2. >50% likelihood of improvement for at least two years

3. >50% likelihood of improvement for at least three years

PAYOR Restenosis: The Continuing Challenge for Peripheral Vascular Intervention

• Most severe in the infrainguinalvessels

• Limited Current Strategies– Cutting balloons– Covered stents– Brachytherapy– Atherectomy– Drug-eluting stents, balloons

• Promising data in early studies– Gene and cell-based therapies

• Remains the greatest unmet need in Vascular Intervention

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Risk Factors for Restenosis

• Female gender• Long-segment disease (>15 cm)• Small caliber artery (≤5 mm)• Extensive calcification • Stent fracture• Poor runoff• Systemic inflammation (e.g. elevated hsCRP)• Diabetes (?)

Strongest Predictors of Endovascular Treatment

Failure in PAD

• POOR SELECTION

• OVERUTILIZATION OF INTERVENTIONS-ESPECIALLY IN CLAUDICATION

TASC A-Endo Rx of choice

TASC D- Surgery Rx of choice

TASC B- Endo preferred

TASC C- Surgery preferred

Relevant in 2015??

Needed to address current limitations– Atherosclerotic burden, calcification– High rates of restenosis– High prevalence of permanent implants; challenges of ISR

Evolution of Balloon Angioplasty for PVI– Improve lumen gain– Reduce dissection– Reduce Restenosis rates

Improvements in stents for femoropopliteal disease– Drug elution to reduce restenosis– Woven nitinol design to increase flexibility and reduce

fracture in highly mobile vessels

Improving Technology for PVI

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no control

no contol

p=.0001

p=.84

p=.01

p=.377

p=.028

p=.01

p=.035

p=.01

p=.227

p=.491

no contol

p=.001

0 20 40 60 80 100 120

Durability I

Durability II

Resilient

Super

ABSOLUTE

FAST

ASTRON

**Thunder

**Fempac

**PACIFIER

**SIROCCO I

**SIROCCO II

STRIDES

Zilver PTX

BMS

DCB

DES

ControlIntervention

Improving Technology for SFA Disease

Lesions in the Regulatory Trials Generally <10 cm (TASC A/B)

Options for TASC C/D SFA Disease

Estimated 2-yr Patency (%)

POBA

PTA+ BMS (or DES)

Atherectomy +/- adjunct

Endoluminal stent graft

Fem-Pop Bypass GraftingVein (AK or BK)

Prosthetic (AK)

Prosthetic (BK)

20-30

30-60

30-50

40-60

70-80

65-80

40-60

CLAUDICATION MATH for Bilateral TASC C/D Disease:

Endo patency 1st limb at 2 years= 0.4-0.6Endo patency 2nd limb at 2 years = 0.4-0.6

Likelihood of Clinical Success at 2 years:Probability of anatomic success in two legs= 0.16-0.36

�150mm FP lesions�50% SES failure

at 1 yr

J Vasc Surg 2012;55:1001-7.

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Armstrong Ej et al Cath Cardiovasc Interv 2013; 82:1168-74

In-Stent Restenosis: The Ongoing Challenge for Vascular Intervention

4% 6%9%

8% 10% 10%12%

17%

10%

18%

23%21% 23% 19% 21%

26%

27%

28%

0%

10%

20%

30%

40%

50%

2003 2004 2005 2006 2007 2008 2009 2010 2011

Critical Limb Ischemia

Claudication

22%

29% 29% 30% 31%

38%

43%

38%

Proportion of all LEB (N=3,504) performed as secondary procedures, By indication and year

72% increase, p<.001

RESTENOSIS IS THE NEW VASCULAR EPIDEMIC

Growing impact of restenosis on the surgical treatm ent of peripheral arterial disease. Jones D et al; JAHA 2013

Impact of Treatment Failure on Surgical Options in PAD

• Many advocate “endovascular first” treatment strategieso Presumed harmless as long as bypass targets

remain intact

o Stakes may increase with each PVI

• However, prior work has suggested that bypass following a failed prior peripheral endovascular intervention (PVI) is associated with poorer outcomeso BASIL trial, Bradbury AW, et al, J Vasc Surg, 2010o Nolan BW, et al, J Vasc Surg, 2011

o Simons JP, et al, J Vasc Surg, 2012

Growing impact of restenosis on the surgical treatm ent of peripheral arterial disease. Jones D et al; JAHA 2013

Propensity score adjustment included approximately 20 patient-level, anatomic and surgical variables

The difference in outcomes is increasing with observation time

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What are the potential explanations for inferior bypass outcomes after

PVI failure?• Systemic Factors (i.e. Bad Patient)

• Being a poor surgical candidate associates with “pushing the envelope” in PVI

• Change in DANA to more distal target

• Embolization of runoff vessels in calf and foot

• Target artery inflammation/injury from catheter and wire manipulations

• Delay in effective revascularization for CLI–further tissue loss, infection worsens limb stage

End of nitinolstent

Fem-tib for limb salvage after failed full metal jacket for claudication(fortunately, did OK)

Was a “bridge burned”? Would 100 of these bypass grafts do as well as 100 fem-pop BPGs?

Is treatment failure worse than the natural progression of disease?

Everything we do has the potential for negative, unintended consequences

Those who don’t manage those consequences may lack full perspective

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In treating lifestyle limiting claudication, shared decision-making should include honest discussions about the durability of the intervention and the likelihood of sustained functional improvement, as well as the possible negative sequelae of treatment failure

Vascular SpecialistsIndustry Professional Societies

Evidence-Based Practice in PAD?

We are going to have to become MORE SELECTIVE about who we treat, and how

we treat them, to demonstrate EFFECTIVENESS and VALUE

[Fewer Procedures, Better Outcomes]