Drug coated/eluting balloons (DCB/DEB) in Coronary and peripheral intervention with a review of evidence and guidelines.

1. DRUG ELUTING BALLOONS
SATYAM RAJVANSHI
Dept. of Cardiology
PGIMER & RML, New Delhi

2. Revolutions in Coronary Intervention – 1st

3. Intimal dissection following ‘POBA’

4. BARE METAL STENT

5. Revolutions in Coronary Intervention – 2nd

6. Restenosis post BMS / DAPT – 4 weeks

7. DRUG ELUTING STENTS

8. Revolutions in Coronary Intervention – 3rd

9. Restenosis post DES

10. But DAPT – 6(?3) to 12 months

11. Revolutions in Coronary Intervention – 4th
BVSDEB

12. What is a ‘DEB’?
• Conventional semi-compliant angioplasty balloons
• Covered with an anti-proliferative drug which is released into the
vessel wall during inflation of the balloon
• Inflation usually at nominal pressures with a specific minimal
inflation time
• Active substance on the DEB is lipophilic with high absorption rate
through vessel wall (to compensate for the short period of contact
between the inflated balloon and the vessel wall)

13. Components of DEB

14. Drug distribution

15. Why Paclitaxel?
• Highly lipophilic – Rapid intracellular uptake and retention in vessel wall for
nearly a week
• Acts by irreversible binding to microtubules, inhibiting cell division and
migration - structural intracellular changes cause long-lasting effects
• Short incubation time (3 minutes) with paclitaxel almost completely inhibits
vascular smooth muscle cell proliferation for up to 12-14 days
• Zotarolimus – Also lipophilic, potential candidate for DCB applications

16. Why this concentration?
• Concentration of paclitaxel on DEB – 3 μg/mm2 – 3x higher compared with paclitaxel-
eluting stents (PES)
• This specific dose is the same for all DEB - based on in vitro studies
• 10% of the dose lost while catheter is advanced through haemostatic valve and guiding catheter
• 70-80% dose released at the target site is washed away in the blood stream during inflation
• Only 10 to 20% of the paclitaxel transferred from balloon surface to the vessel wall
• Thus, PCB delivers a dose to target in a very short time that is higher than total dose
released by DES over many weeks
• With this immediate drug release - no need for a polymer for drug administration -
thus avoiding chronic inflammation and late thrombosis

17. 1st generation DEBs
• Paccocath (Bayer, Germany)
• Sequent Please (Braun, Germany)
• Paclitaxel (3 ug/mm2) mixed with Drug carrier applied on balloon
surface, an iodinated hydrophilic contrast – IOPROMIDE - increases drug
solubility and speeds uptake
• Paclitaxel maximum concentration in IOPROMIDE – 20x than in saline

18. 2nd generation DEBs
• In.Pact Falcon (Invatec, Italy) - Paclitaxel (3 ug/mm2) mixed with Hydrophilic
spacer molecule covering balloon – UREA
• Dior II (Eurocor, Germany) - Paclitaxel (3 ug/mm2) mixed with a hydrophilic
resin ‘SHELLAC’ that opens its structure when in contact with the tissue on
balloon inflation, allowing quick release
• Pantera Lux (Biotronik, Germany); Danubio (Minvasys, France) - Paclitaxel (3
ug/mm2) mixed with BTHC (Butyry trihexyl citrate) – breaks the crystalline
paclitaxel structure – rapid absorption

19. 3rd generation DEBs
No carrier PEBs!
• Elutax (Aachen Resonance, Germany) – Paclitaxel 2 ug/mm2 inside hydrogel
coat which sticks to intima on deflation and decreases systemic washoff
• Protégé (Blue Medical, Netherlands) – No carrier – Very tight bound
paclitaxel in between balloon folds

22. Practical points before DEB use
• Proper vessel preparation with predilation balloon 0.5-1.0 mm smaller than
intended DEB
• Ensure adequate 1:1 sizing between vessel and DEB (IVUS in coronaries,
EVUS in peripherals)
• Shorten transfer time from access sheath to DEB inflation
• Single prolonged inflation for complete drug release till manufacturer’s
recommended time (60 or 30 sec) – if not tolerated, fractional release in
quick intermittent inflations till recommended time is complete

23. DEB in CAD

24. INDICATIONS and EVIDENCE
1. In-stent restenosis - BMS

25. INDICATIONS and EVIDENCE
1. In-stent restenosis - DES

26. INDICATIONS and EVIDENCE
1. In-stent restenosis - DES

27. INDICATIONS and EVIDENCE
1. In-stent restenosis - DES

28. INDICATIONS and EVIDENCE
1. In-stent restenosis
ESC guidelines on myocardial revascularization
2014

29. INDICATIONS and EVIDENCE
2. De Novo lesions: Small vessels

30. INDICATIONS and EVIDENCE
2. De Novo lesions: Small vessels

31. INDICATIONS and EVIDENCE
3. De Novo lesions: Bifurcation
• 2 strategies
i. Sequential DEB treatment of the bifurcation branches followed by BMS
implantation in the MB – RCT available
ii. Simple MV stenting followed by kissing DEB – Recent with sparse evidence

32. INDICATIONS and EVIDENCE
3. De Novo lesions: Bifurcation

33. INDICATIONS and EVIDENCE
3. De Novo lesions: Bifurcation

34. • Sequential application of DCB (and not pre-mounted BMS) for
treatment of de novo coronary lesions resulted in efficient
inhibition of neointimal hyperplasia.
• The sequence of application (DCB first vs. BMS first) did not seem
to influence the outcome (6 months late loss 0.45±0.57 mm vs.
0.53±0.52 mm, p=0.83), except for better apposition in BMS first
(p=0.013).
INDICATIONS and EVIDENCE
4. De Novo lesions: DEB + BMS

35. INDICATIONS and EVIDENCE
4. De Novo lesions: DEB + BMS

36. INDICATIONS and EVIDENCE
4. De Novo lesions: DEB + BMS

37. ESC guidelines on myocardial revascularization
2014
For small vessel PCI or Bifurcation PCI with DEB
- No level of recommendation given!
Use of DEB in any other coronary indication than ISR
- No level of recommendation given!
INDICATIONS and EVIDENCE
De Novo lesions

38. Most promising indications for DEB in CAD
• ISR in BMS/DES
• De novo lesion in small vessels (<2.5 mm)
• In patients with contraindication(s) to prolonged DAPT

39. DEB in PAD

40. Current scenario in PAD intervention
• Surgical bypass is still gold standard – but endovascular
innovations like DEB, DES, Endografts are fast developing
• Endovascular Rx advantages are shorter hospital stay, less wound
infection and lower peri-op mortality compared with open surgery
• But Late clinical failure due to restenosis, neo-intimal hyperplasia,
and stent fracture still a major problem

41. POBA
• POBA 1st line treatment for femoro-popliteal disease
• Stenting only for poor outcome – high rate of re-stenosis despite
initial technical success rate of 95% even with stenting 1 year
restenosis rates have varied between 20-50% depending on an
increasing with length of lesion
• Balloon angioplasty for shorter lesions(<4cm)
• Primary stenting in longer lesions
• Secondary stenting if residual stenosis/dissection

42. DEB
• Similar rationale and technology
• Same drug concentration
• Somewhat longer inflation times (upto 180 sec)

43. DEB in FEMORO-POPLITEAL DISEASE
• Many RCT showing favourable results vs POBA (upto 2 yrs)
• But have short follow up, industry driven
• Secondary stent implantation: 4-21% in DEB; 14-36% in POBA
• IN.PACT Admiral (Medtronic, USA) platform demonstrates greater
efficacy

45. DEB in INFRA-POPLITEAL DISEASE
IDEAS RCT
• DCB vs DES
• Binary restenosis in DES 28% vs DCB 57.9% at 6 months
IN.PACT DEEP Trial
• DEB vs POBA
• Comparable efficacy but trend towards higher amputation rate in DEB.
Balloon withdrawn (IN.PACT Amphirion – Medtronic)

46. General guideline

47. Conclusions

48. Conclusions
• DEB is a promising technology in both coronary and peripheral
artery disease
• NOT suitable for all - For technical success, requires proper
patient selection – clinical and angiographic characteristics,
proper preparation of vessel before use

49. References
• Textbook of interventional cardiology 7th Ed. By Topol and Terstein. 2015
• Rafael Sant’Anna Athayde G et al. Applications of the Drug-Eluting
Balloon in Coronary Artery Disease. Rev Bras Cardiol Invasiva.
2014;22:293-9.
• Vaquerizo B etal. Update on drug-eluting balloons for percutaneous
coronary interventions. EMJ Int Cardiol. 2013;1:80-90.
• Colombo A. Drug eluting balloons for femoro-popliteal artery disease:
Emerging research. ESC E journal cardiology practice 2014;13.
• Siablis D et al. JACC INTV 2014;7:1048-56.