DRUG COATED BALLOONS.pptx

1. DRUG
COATED
BALLOONS
BY:
DR. PARAG GUPTA

2. DCB Concept
Drug coated balloons (DCBs) –
Fast and homogenous transfer
of antiproliferative drugs into
vessel wall during single
balloon inflation by means of
lipophilic matrix
DCB-only PCI is the concept of
treating coronary stenoses
while limiting need for
permanent/semipermanent
implants
Potentially every PCI should
aim at using the DCB-only
strategy
"Leave nothing behind"

3. DCB Concept
OCT studies have shown 40 – 56% lesions treated with DCB had late
luminal enlargement at 6 – 8 month follow-up.
DCB: A balloon catheter, a highly lipophilic drug, and a coating matrix
that regulates local drug delivery to the vessel wall.
Requirements of successful non-stent-based approaches for local drug
delivery:Rapid drug uptake by the tissue.
Drug persistence in the vessel wall to compensate for short contact
time.

4. Drugs Used for Suppression of Neointimal
Proliferation
1. Taxane compounds like protaxel and paclitaxel
• Absorbs quickly
• Localizes in subintimal space
• Partitions significantly in adventitia
2. Rapamycin derivatives like sirolimus and zotarolimus
• Limitations:
• Poorer transfer rate compared to paclitaxel rapid decrease of tissue
→
concentrations
• Reversible binding to rapamycin receptor shorter duration of action
→

5. Drugs Used for Suppression of Neointimal
Proliferation
Advances in Rapamycin Derivatives:
1.Sirolimus in liquid formulation delivered by a porous balloon (SABRE trial)
2.Encapsulation of sirolimus in phospholipids
3.Crystalline Sirolimus coating with butylated Hydroxytoluene as excipient
4.Microreservoirs using biodegradable polymer
5.Nanoparticles using biodegradable polyester-based polymers

6. No Class Effect!
Significant
differences in
antiproliferative
drugs:
Dose Release kinetics
Coating used
Tissue
concentrations
Cannot expect a
class effect among
various DCB
technologies.

7. Commercially available or under investigation DCBs for CAD
Device Company Drug Dose (µg/mm²) Additive
SeQuent Please Neo B. Braun Paclitaxel 3.0 Iopromide
Agent Boston Scientific Paclitaxel 2.0 Acetyl tributyl citrate
Prevail Medtronic Paclitaxel 3.5 Urea
Pantera Lux Biotronik Paclitaxel 3.0 n-Butyryl citrate
RESTORE Cardionovum Paclitaxel 3.0 Shellac
Elutax SV Aachen Resonance Paclitaxel 2.2 None
Magic Touch Concept Medical Sirolimus 1.3 Phospholipid
Selution Med Alliance Sirolimus 1.0 Micro-reservoirs
Virtue Caliber Therapeutics Sirolimus N/A Nanoparticles
SeQuent SCB B. Braun Sirolimus 4.0 Crystalline

8. Indications for DCB
• Instent Restenosis
• Small vessel disease
1. Approved:
• Tortuous vessel
• Bifurcation lesions
• Large vessel de novo lesions
• Diffuse long lesions
• Calcified lesions
• Acute Coronary Syndrome
• High bleeding risk
2. Prospective:

9. DCB for In-Stent Restenosis
• Avoids multiple layers of metallic stents
• Class of Recommendation I, Level of Evidence A
Types of ISR:
• BMS-ISR: Characterized by excessive neointimal proliferation (i.e.,
hyperplasia)
• DES-ISR: Characterized by neoatherosclerosis due to insufficient effect or
failure of antiproliferative drugs
• Intracoronary imaging, preferably OCT, is recommended to identify
underlying causes of ISR

10. RCTs Comparing DCB and DES for ISR
Trial (Year)
Comparator
(N)
Primary Endpoint F/U (Months) Results
BMS-ISR
RIBS V (2014) EES (189) MLD at 9 months (angio) 12
MLD: DCB 2.01 mm vs. EES 2.36 mm (p < 0.01)
MACE: DCB 9% vs. EES 6% (p = 0.65)
SEDUCE (2014) EES (50)
Uncovered strut (%) at 9 months
(OCT)
12
DCB 1.4% vs. EES 3.1% (p = 0.03)
Binary restenosis: DCB 9.1% vs. EES 0% (p =
0.15)
DES-ISR
RIBS IV (2015) EES (309) MLD at 9 months (angio) 12
MLD: DCB 2.03 mm vs. EES 1.80 mm (p < 0.01)
MACE: DCB 20.1% vs. EES 12.3% (p = 0.04)
RESTORE (2018) EES (172) In-segment LLL (angio) 12
MLD: DCB 0.15 mm vs. EES 0.19 mm (p = 0.54)
MACE: DCB 7.0% vs. EES 4.7% (p = 0.51)
Mixed-ISR

11. DCB in Small Vessels
• Definition: Small vessel disease is defined as < 3.0 mm in reference vessel diameter.
• Impact:
• Late lumen loss occupies a greater percentage of the respective vessel diameter.
• Leads to higher rates of ISR (in-stent restenosis) and adverse events.
Key Trials & Findings
• BASKET – SMALL 2 Trial
• Showed paclitaxel-iopromide-coated stents were non-inferior to 2nd Gen DES.
• RESTORE-SVD (China) Trial
• Showed DCB non-inferior to Resolute Integrity DES in terms of:
• Percentage diameter stenosis at 9 months.
• Comparable target lesion failure rates at 1 year.
• Conclusion: Adequate lesion preparation is mandatory.

12. DCB in de novo Large Vessel Lesions
Key Clinical Trials & Findings
• DEBUT Trial
• Comparison: DCB vs. BMS in individuals with high bleeding risk (HBR).
• 9-month outcomes:
• No acute vessel closure
• 1% MACE (Major Adverse Cardiac Events)
• PEPCAD NSTEMI Trial
• Comparison: DCB vs. BMS/DES
• Findings:
• DCB demonstrated non-inferiority compared to metallic stents.
• However, 15% of patients required "bail-out" stenting.
• ALLIANCE Registry
• Ongoing study evaluating the use of DCB for de novo large vessel lesions.
Current Indications for DCB Use
1. Patients with High Bleeding Risk (HBR).
2. Lesions where DES efficacy is uncertain, such as:
1. Ostial LCx (Left Circumflex Artery).
2. Jailed side branches.

13. DCB in Bifurcation Lesions
• Accounts for 20% of cases undergoing PCI.
• Single cross-over stenting in the main vessel with side branch balloon
dilatation or provisional stenting.
• DCB after ostial side branch balloon dilatation reduced:
• late lumen loss (0.13 mm vs 0.51 mm)
• binary restenosis (6% vs 26%)

14. DCB in bifurcation lesions
DCB-only approach for bifurcation lesions is appealing because it avoids carina
shift but is technically challenging, with the possibility of dissection or
perforation after kissing balloon dilatation.
DCB with DCA (Directional coronary atherectomy) is a good option to avoid
metal.
At 12 months:
• TLF – 10.9%
• Binary restenosis – 2.3%

15. DCB in diffuse long lesions
Long (> 60 mm) lesions often require overlapping stents – higher
restenosis/stent thrombosis
Vessel geometry altered because of tackling curves and natural step-down of
vessel diameter
• Full metal jacket undesirable especially in young patients in view of need of
future CABG

16. DCB in diffuse long lesions
"Hybrid approach" – combines DES (proximal) and DCB (distal)
DCB-only vs Hybrid approach – comparable rate of
• MACE (20.8% vs 22.7%; p = 0.74)
• TLR (9.6% vs 9.3%; p = 0.84)
• HYPER pilot study will evaluate 12-month clinical outcomes of a Hybrid
(DES/DCB) approach in 100 patients with diffuse CAD

17. DCB in calcified lesions
"Achilles heel" of PCI even in DES era due to
• stent underexpansion
• vessel wall overstretch leading to medial injury or disruption
• damaged polymer coatings
• strut fractures
• delayed arterial healing response
• DCB-only approach under investigation but appears promising as metal-free
artery leaves additional therapeutic choices

18. DCB in Acute Coronary Syndromes
REVELATION trial found DCB-only strategy is not inferior to DES in terms of FFR
at 9 months in 120 pts with STEMI undergoing primary PCI
• 1 case had abrupt closure
• 1 case required TLR
• PEPCAD NSTEMI trial showed no difference in TLF

19. DCB in Acute Coronary Syndromes
Limitations of DCB in ACS
• Thrombus could obstruct distribution of antiproliferative drugs to vessel wall
• Dissection
• Elastic recoil
• Vasospasm
• Thrombus formation
• Metallic DES reported to be more frequently associated with incomplete stent
apposition and uncovered struts in STEMI than CCS

20. DCB in High Bleeding Risk (HBR) patients
• 64% of Japanese patients undergoing PCI met the Japanese HBR criteria.
• "Leave nothing behind" or "stentless" approach appears appealing.
• Current Japanese guidelines recommend 1 – 3 months DAPT for CCS
patients treated with a DCB-only strategy (COR IIa, LOE B).
• Short-duration DAPT significantly reduces the risk of major bleeding
without compromising the risk of thrombosis.

21. Lesion Preparation for DCB Use
• Optimal lesion preparation is of paramount importance to maximize the effect of DCB.
Adequate angiographic findings defined as:
• TIMI grade 3 flow
• Residual stenosis < 30%
• Absence of major dissections (i.e., NHLBI classification type C-E)
HOST-ISR-DCB Cohort Study Findings:
• Fully optimized procedures had a significantly lower incidence of TLF within 2 years compared to
partially or non-optimized procedures.
• Balloon-stent ratio > 0.91
• Total inflation time > 60s
• Residual stenosis < 20%

22. Lesion Preparation for DCB Use
Adjuvant Techniques for Lesion Preparation:
• Scoring balloon
• Cutting balloon
• Rotational atherectomy
• Excimer laser
Note: Orbital atherectomy and intracoronary lithotripsy (IVL) not recommended for ISR.
Dissection Assessment:
• When major dissections are suspected, IVUS (Intravascular Ultrasound) is safer than OCT to estimate
severity.
Functional Assessment for DCB Strategy:
• May aid decision-making for DCB-only strategy.
• Routine Cutoffs:
• FFR > 0.90
• Coronary Flow Reserve (CFR) > 2.5 (better clinical outcomes post-balloon angioplasty).
• For DCB, FFR can be safely lowered to > 0.80.

23. Lesion
Preparatio
n for DCB
Use

24. Geographic Miss
• Defined as an injured area not covered by radiation/stent, potential substrate
of recurrent restenosis (candy wrapper effect) during
brachytherapy/covered stent era.
• Unfavourable edge vascular responses (EVR) problem in DES era also.
• Modified balloons (cutting balloon or scoring balloon) associated with
significantly lower rates of TLR rates in REDUCE III trial.
• These balloons recommended for better lesion preparation to reduce risk of
balloon slippage or unplanned “bail-out” stenting.
• Predilated segments should be thoroughly covered by DCB considering
mechanical damage to vessel wall.

25. Limitations/Concerns regarding DCB
1. Larger profile than that of conventional balloons.
1. Possibility of system delivery failure to the lesion.
2. Drug loss due to friction with irregular vessel surface.
3. Use of guide extension catheters (GEC) for quick and easy delivery of DCB system.
2. Higher mortality observed in patients with lower extremity arterial disease (LEAD) treated
with paclitaxel stents or balloons.
1. DAEDALUS study showed that incidence of all-cause mortality was comparable
between paclitaxel DCBs and repeat stenting with DES.
2. A study showed paclitaxel DCBs did not have increased mortality at 2 years & had
lower all-cause mortality at 3 years as compared to DES.
• Rapamycin-based DCBs expected to alleviate safety concerns associated with Paclitaxel
DCBs.

26. Limitations of DES
1. Vascular inflammation, hypersensitivity to metal/polymer leading to Acute stent
thrombosis
2. Unequal drug distribution
3. Late occurrence of neoathersclerosis and stent thrombosis
4. Hampers future CABG options
5. Late luminal enlargement and restoration of vasomotor function are both
compromised by the permanent metallic cage
6. Long term requirement of DAPT

27. Take home message
• Temporary halt in development of bioresorbable scaffold (BRS) might motivate to maintain the
"leave nothing behind" concept using DCB
• Currently, 3 indications for DCBs are evidence based
• ISR
• HBR
• Small vessels
• Studies are underway to evaluate DCBs in other situations like
• De novo lesions in large vessels
• Bifurcation lesions
• Calcified lesions
• Acute coronary syndrome
• Diffuse long lesions

28. THANK YOU