The document discusses the advantages and limitations of drug-coated balloons (DCBs) in interventional cardiology, highlighting their potential to treat vascular conditions without leaving permanent implants. It provides insights into various antiproliferative drugs used, efficacy in different lesion types, and the importance of optimal lesion preparation before DCB application. Additionally, ongoing studies are outlined to assess DCB performance in complex cases like bifurcation lesions and acute coronary syndromes.

1. Drug Coated Balloons
Dr Aniruddha Dharmadhikari
Interventional Cardiologist
Ex Prof of Medicine, MVP Medical College, Nashik.
Cardiologist, Shree Sai Baba Heart Institute, Nashik.

2. 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
Limitations of DES

3. 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”
DCB Concept

4. 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
1. Rapid drug uptake by the tissue
2. Drug persistence in the vessel wall to compensate short
contact time
DCB Concept

5. 1.Taxane compounds like protaxel and paclitaxel
Advantages: Absorbs quickly, localizes in subintimal space
and 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
Drugs used for suppression of
neointimal proliferation

6. 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 basedpolymers
Drugs used for suppression
of neointimal proliferation

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

8. 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
Commercially available or under
investigation DCBs for CAD

9. 1. Approved:
i) Instent Restenosis
ii) Small vessel disease
2. Prospective:
i) Tortuous vessel
ii) Bifurcation lesions
iii) Large vessel de novo lesions
iv) Diffuse long lesions
v) Calcified lesions
vi) Acute Coronary Syndrome
vii) High bleeding risk
Indications for DCB

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

11. 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
DARE (2018) EES (278) MLD at 6 months (angio) 12
MLD: DCB 1.72 mm vs. EES 1.84 mm
(p = 0.02)
MACE: DCB 10.9% vs. EES 9.2%
(p = 0.66)
RCTs comparing DCB and DES for ISR

12. Small vessel disease defined as < 3.0 mm in reference vessel diameter
Late lumen loss occupies a greater percentage of respective vessel
diameter resulting in higher rates of ISR and adverse events
BASKET – SMALL 2 Trial showed paclitaxel-iopromide-coated stents
non-inferior to IInd Gen DES
RESTORE-SVD China showed DCB non-inferior to Resolute Integrity
DES in terms of
- percentage diameter stenosis at 9 months and
- comparable target lesion failure rates at 1 year
Adequate lesion preparation mandatory
DCB in Small Vessels

13. DEBUT Trial - DCB vs BMS in individuals with high bleeding risk (HBR).
At 9 months,
- no acute vessel closure
- 1% MACE
PEPCAD NSTEMI Trial – DCB vs BMS/DES, non inferiority of DCB
compared to metallic stents
However, 15% patients required “bail-out” stenting
ALLIANCE registry ongoing to decide on use of DCB for de novo large
vessel lesions
Presently indications are:
i. Patients having HBR
ii. Lesions for which clinical efficacy of DES is not well
established (ostial LCx or jailed side branch)
DCB in de novo large vessel lesions

14. Accounts for 20% 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%)
DCB in bifurcation lesions

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

16. 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
DCB in diffuse long lesions

17. “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
DCB in diffuse long lesions

18. “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
DCB in calcified lesions

19. 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
DCB in Acute Coronary Syndromes

20. 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
DCB in Acute Coronary Syndromes

21. 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 DCB-only strategy (COR
IIa, LOE B)
Short duration DAPT significantly reduces risk of major
bleeding without compromising risk of thrombosis
DCB in High Bleeding Risk (HBR) patients

22. Optimal lesion preparation of paramount importance to maximize 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 found fully optimized procedures had
significantly lower incidence of TLF within 2 years than partially or
non-optimized procedures
- Balloon-stent ratio > 0.91
- Total inflation time > 60s
- Residual stenosis < 20%
Lesion preparation for DCB use

23. Adjuvant techniques for lesion preparation
- scoring balloon
- cutting balloon
- Rotational atherectomy
- Excimer laser
Orbital atherectomy and intracoronary lithotripsy (IVL) not recommended for ISR
When major dissections suspected, IVUS rather than OCT safer to estimate severity of
dissection
Functional assessment may be an option to aid decision making for DCB-only strategy
Routinely, FFR > 0.90 and Coronary flow reserve (CFR) > 2.5 identified as cutoff
predicting better clinical outcomes following conventional balloon angioplasty
For DCB, it can be safely lowered to FFR > 0.80
Lesion preparation for DCB use

24. Lesion preparation for DCB use

25. 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
Geographic Miss

26. 1. Larger profile than that of conventional balloons.
- Possibility of system delivery failure to the lesion
- Drug loss due to friction with irregular vessel surface
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
- DAEDALUS study showed that incidence of all-cause mortality
was comparable btn paclitaxel DCBs and repeat stenting with DES
- A study showed paclitaxel DCBs did not have increased mortality
at 2 yrs & had lower all-cause mortality at 3 yrs as compared to DES
Rapamycin based DCBs expected to alleviate safety concerns associated
with Paclitaxel DCBs
Limitations/Concerns regarding DCB

27. 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
Take home message