DRUG ELUTING BALLOONS

SATYAM RAJVANSHIDept. of Cardiology

PGIMER & RML, New Delhi

Revolutions in Coronary Intervention – 1st

Intimal dissection following ‘POBA’

BARE METAL STENT

Revolutions in Coronary Intervention – 2nd

Restenosis post BMS / DAPT – 4 weeks

DRUG ELUTING STENTS

Revolutions in Coronary Intervention – 3rd

Restenosis post DES

But DAPT – 6(?3) to 12 months

Revolutions in Coronary Intervention – 4th

BVSDEB

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)

Components of DEB

Drug distribution

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

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

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

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

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

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

DEB in CAD

INDICATIONS and EVIDENCE1. In-stent restenosis - BMS

INDICATIONS and EVIDENCE1. In-stent restenosis - DES

INDICATIONS and EVIDENCE1. In-stent restenosis - DES

INDICATIONS and EVIDENCE1. In-stent restenosis - DES

INDICATIONS and EVIDENCE1. In-stent restenosis

ESC guidelines on myocardial revascularization 2014

INDICATIONS and EVIDENCE2. De Novo lesions: Small vessels

INDICATIONS and EVIDENCE2. De Novo lesions: Small vessels

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

INDICATIONS and EVIDENCE 3. De Novo lesions: Bifurcation

INDICATIONS and EVIDENCE 3. De Novo lesions: Bifurcation

• 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 EVIDENCE4. De Novo lesions: DEB + BMS

INDICATIONS and EVIDENCE4. De Novo lesions: DEB + BMS

INDICATIONS and EVIDENCE4. De Novo lesions: DEB + BMS

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 EVIDENCEDe Novo lesions

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

DEB in PAD

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

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

DEB

• Similar rationale and technology

• Same drug concentration

• Somewhat longer inflation times (upto 180 sec)

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

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)

General guideline

Conclusions

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

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.