1. Current Results of Drug Coated Balloons for Infrapopliteal Disease
Kenneth Rosenfield, MD
Massachusetts General Hospital Boston, Massachusetts

2. Kenneth Rosenfield, MD
Consulting: Complete Conference Management, AngioDynamics, Inc.,
Bard Peripheral Vascular, Inc. and The Medicines Company.
Grant Support: Atrium Medical Corporation, Abbott Laboratories, Cordis Corporation, IDEV Technologies, Inc., Lutonix, Inc. and Bard Peripheral Vascular, Inc.
Honoraria: VIVA Physicians
Stocks, Stock Options, other ownership interest: VORTEX, ICON Interventional Systems, Medical Simulation Corporation, Contego and CardioMEMS, Inc Off-Label: May discuss off-label use of devices occasionally employed in carotid revasc.

3. The Implications of CLI
“We often see a man pass away by degrees, and limb by limb lose the sensation of life: first the toes of the feet grow livid, next die the feet and legs, afterwards over the other limbs go creeping the cold footsteps of death...”
-Leviticus (96-55 BC)

4. Infrapopliteal Intervention Indications
Treat Ischemic rest pain
Facilitate healing of ulcer/gangrene (where foot is salvageable
Lower level of amputation
Facilitate healing of amputation site
Treat severe claudication that interferes with ADL’s
“Less certain”
Treat moderate life-style limiting claudication
Provide better outflow to maintain proximal device patency

5. Infrapopliteal Intervention Defining success
Elimination of pain
Limb healing and salvage
Improved ambulation
Improved functional status
Improved quality of life
Reduced mortality
Relationship angiographic patency to above?

6. Infrapop Intervention Achieving goals and measuring outcome
Requirement for effective wound-healing (generally)
Establish continuous, pulsatile, “in-line” flow to the pedal vessels (at least one)
Patency must last at least long enough to achieve wound-healing

7. Is long term patency needed for ulcer healing ?
Optimal vascularisation
Patent
Vascularisation
Restenosis
Revascularisation
Metabolic need
Trauma
Time needed for healing
Vermassen F 2010

8. Special Technical Considerations (challenges) for Infrapop Intervention
Heavy plaque burden and diffuse nature of disease
Small diameter of vessels (diabetics)
Calcification
Prevalence of occlusions…often lengthy
Presence of collaterals (reducing flow in parent vessel)
Aggressive restenosis

9. For Certain Territories, No Matter How Good the Initial Result, Mechanical Treatments Alone Do Not Last
8 mos later – rest pain
Laser/PTA
Pre
Post

11. DCBs: Why All the Hype? Potential to fulfill unmet clinical needs…
Eliminate liability associated with permanent implant
Chronic inflammation, stimulus for hyperplasia & ISR
Issue of repeat access & subsequent intervention
Fracture
Treatment of “no-stent” zones
Reduce need for anti-platelet therapy (DAPT)
Simplicity? Cost reduction? Better safety profile?
More practical than stents & other devices for BTK

12. Drug-Coated Balloon Trials in SFA 6-Month Mean Late Lumen Loss Comparison
(median 0.2)
(median 1.1)
(median 0.3)
(median 0.8)
LEVANT I
THUNDER1
FemPac2
1 Tepe G, et al. N Engl J Med. 2008;358:689–699.
2 Werk M, et al. Circulation. 2008;118:1358 –13565.

13. DCB: Histopathology Studies
Endothelialization complete at 28 days
Sustained drug effects in deeper layers through 90 days
Little inflammation
Healing predominates b/n 90 & 180 days
No significance downstream effects
…Favorable safety profile!

16. DCB for BTK: CLI Indication Schmidt et al.
Clinical Status: Baseline vs. 1 year
109 limbs
176 +/- 88mm2
27.4% restenosis at 3 months (67% in historic control)
17.3%TLR at 12 months (50% in control)
Clinically improved 92%
Wound healed 74.2%
95.6% limb salvage
16% mortality
Restenosis  focal, when occurred
Schmidt, et al. JACC. 2011; 58:
Drachman

21. Drug-Device Combinations
Drug-coated balloons
Balloon alone
With cutting balloon
With stent
With atherectomy
Drug-eluting stents
Biodegradable stents (+/- drug)
Device-delivered cell therapy

22. Upcoming Trials: Atherectomy and Drug-Coated Balloon Angioplasty in Treatment of Long Infrapopliteal Lesions (ADCAT)
Sponsor:Herz-Zentrums Bad Krozingen (PI’s: Aljoscha Rastan Thomas Zeller)
Single-center, prospective, randomized study (Bad Krozingen, Germany)
80 subjects (ages 50-85) with long de-novo stenosis (≥6cm) and symptomatic peripheral artery disease (Rutherford 3, 4, or 5)
Randomized 1:1
drug-coated balloon angioplasty alone vs. atherectomy plus drug-coated balloon angioplasty
Primary endpoint: In-Segment Binary Restenosis, assessed by repeat angiography at 3 months
Secondary endpoints: TLR and change in Rutherford-Becker at 6 and 12 mos
Follow-up visits 3, 6, 12 months.

23. DCB for BTK: Conclusions
Proven “class” effect
Drug delivery to deep layers after single contact (dependent on good carrier)
Punctuated delivery sustained release
Appears to be safe…need more data
Many potential advantages
Reduce restenosis; no stent; avoid DAPT, etc.
Initial angiographic and clinical results promising
Adoption already high OUS
Cost unknown
Much more comparative data required