Download Coated balloons

CACVS 2012,
Paris, January 21 2012
Coated balloons: how does it work,
what are the results?
Jos C. van den Berg, MD PhD
Ospedale Regionale di Lugano, sede Civico
Lugano
Fiction?
Drug Eluting Balloon: Concept
• Local delivery of drug exactly on site,
avoids systemic exposure
– Effective concentration can be achieved
– Exact control of dose possible
DES vs. DEB
Drug-Eluting Stent
•
•
•
•
•
Slow release
Persistent drug
exposure
~ 100 - 200 µg dose
(Polymer)
Stent mandatory
Drug-Eluting Balloon
•
•
•
•
•
•
Immediate release
Short-lasting exposure
~ 300 - 600 µg dose
No polymers
Premounted stent
optional
Matrix optional
Heart 2007, 93: 539-41
Advantages DEB
• Homogeneous drug transfer
• Concentration highest at time of injury
– Prevents initiation of chain of events leading
to neointimal proliferation
• Absence of stent struts
– Limited need for dual antiplatelet therapy
• Respects original anatomy and diminishes
abnormal flow pattern
Advantages DEB
• Preserves follow‐up treatment options
• Feasible in situations where stents are
undesirable
– Small vessel (BTK)
– In‐stent restenosis
– Long or distal BTK lesions (stent
compression)
Mechanism of action
• Most currently available drug-eluting
balloons use dry state paclitaxel (active
ingredient of Taxol®; typical dosage in
oncology about 300 mg/ patient)
• Pharmacokinetically paclitaxel drug of
choice
– highly lipophilic, rapid cellular uptake and
retention at site of delivery
• Dose used in DEB 2 µg/mm2 or 3 µg/mm2
of the balloon surface
Mechanism of action
• Paclitaxel is a potent inhibitor of smooth
muscle cell proliferation, SMC migration,
and extracellular matrix formation in vitro,
with all three phases of the restenosis
process inhibited effectively
• The effective transfer of drug to the arterial
wall is controlled by how the drug is
loaded on the balloon (coating
engineering) and the relative solubility of
the drug between cell wall and coating
Matrix
• Contrast agent iopromide is used as a
hydrophilic spacer (Paccocath); in this way
the solubility of paclitaxel is increased and
the transfer of paclitaxel to the vessel wall is
enhanced
• FreePac coating (Medtronic Invatec) uses
urea as a matrix to improve adherence of the
drug to the balloon and facilitates drug elution
by separating paclitaxel molecules and
balancing hydrophilic and lipophilic properties
Matrix
• Natural resin (composed of shellolic and alleuritic
acid; Shellac coating, Eurocor). Once in contact
with blood the hydrophilic network of the
composite swells and opens the structure to allow
pressure-induced release of paclitaxel
• Butyryl-tri-hexyl citrate (BTHC) (Biotronik) :
compound used in medical devices & cosmetics,
approved to be dissolved into the blood and used
in the body, degrades to citric acid and alcohol;
disrupts the crystalline structure of paclitaxel and
makes the compound absorbable to the tissue
Treatment with DEB
• Predilation always
• Balloon length > lesion length
• Inflation time recommended for optimal
release of the drug (up to 80% of the total
amount) is between 30 and 60 seconds
(shorter inflation should be avoided in all
cases, longer inflation times will not lead to
a significant additional release of drug)
Treatment with DEB
• Caveat: geographic miss
• In long lesions: overlapping balloons (no
issue with increase in local dose)
• Upgrade introducer at least 1F
DEB ZONE
How to prevent geographic miss
How to prevent geographic miss
Available catheters
Company
Catheter
Coating
Dose (µg/ mm²)
MEDRAD
Cotavance® DEB
Paclitaxel/Iopromide
3
Medtronic Invatec
In.Pact™ series
Paclitaxel/Urea
3
Aachen Resonance
Elutax™
Paclitaxel/No Carrier
2
Eurocor
Freeway™
Paclitaxel/Shellac
3
Lutonix
Moxy™
Paclitaxel/unknown carrier
2
Cook
Advance-18™
Paclitaxel/unknown carrier
3
Biotronik
Passeo 18 Lux™
Paclitaxel/BTHC
3
Data
• Animal studies
• Coronary applications
• Peripheral applications
Animal studies
Inflation time and dosage
(pre-clinical porcine coronary arteries)
• Even very short inflation time sufficient to
achieve desired effect (advice 30-60 sec)
• No specific risk if a higher dose is applied
(overlapping balloons)
co
ntr
ol
Paclitaxel balloon Ac
10 sec
Paclitaxel balloon Ac
2 Paclitaxel balloons Ac
120 sec
60 sec each
Cremers B et al, Thromb Haemost. 2009 ;101:201-206
Are all DEB’s equal?
Are all DEB’s equal?
Cremers B et al, Clin Res Cardiol 2009; DOI 10.1007/s00392-009-0008-2
Pilot study (FemPac)
• The 6-month follow-up angiography performed
in 31 of 45 and 34 of 42 patients showed less
late lumen loss in the coated balloon group
(0.5±1.1 versus 1.0±1.1 mm; P=0.031)
• The number of target lesion revascularizations
was lower in the paclitaxel-coated balloon group
than in control subjects (3 of 45 versus 14 of 42
patients; P=0.002)
• Paclitaxel balloon coating caused no obvious
adverse events and reduced restenosis in
patients undergoing angioplasty of femoropopliteal arteries
Impossible d’afficher l’image.
THUNDER
• 154 patients
• 3 treatment arms
– Paclitaxel-coated balloons (3 µg/mm2)
– Uncoated balloons with paclitaxel in contrast
medium
– Uncoated balloons (control)
Tepe G et al, NEJM 2008;358:689-699
THUNDER
• Late lumen loss
–
–
–
–
Paclitaxel-coated balloons 0.4±1.2 mm
Control group 1.7±1.8 mm (P<0.001)
Paclitaxel in the contrast medium 2.2±1.6 mm (P =0.14)
NB more stents used in control group (LLL paclitaxel-coated
balloons 0.3±1.1mm vs. 1.9±1.8 mm control; P<0.001)
• Angiographic restenosis rate
– Paclitaxel-coated balloons 17%
– Control group 44% (P = 0.01)
– Paclitaxel in the contrast medium 55% (P = 0.39; as compared to
control)
Tepe G et al, NEJM 2008;358:689-699
THUNDER conclusions
• Use of paclitaxel coated balloon catheters
significantly lowered the incidence of
restenosis at 6 months and the rate of
target-lesion revascularization at 6, 12,
and 24 months
• Addition of paclitaxel to the angiographic
contrast medium did not have a significant
effect
Tepe G et al, NEJM 2008;358:689-699
AFS-LEVANT
Scheinert D, et al TCT 2010
AFS-LEVANT
Scheinert D, et al TCT 2010
Pacifier
Werk M, et al CIRSE 2011
Pacifier
Werk M, et al CIRSE 2011
DEB BTK
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•
•
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Registry Leipzig 104 patients (109 limbs)
Mean lesion length 176 ± 88 mm
77.1 % occlusion, 12.9 % stenotic disease
Follow-up comprised angiography after 3
months and clinical follow-up at 3, 6 and 12
months
• Three month follow-up n=100 (7 patients
died: 1 due to major amputation, 6
cardiovascular deaths)
Schmidt A, et al J Am Coll Cardiol 2011;58:1105-9.
DEB BTK
• 93 patients were alive within the 3 months
follow-up window
• 84 lesions had a control diagnostic
angiography available
• Clinical improvement was seen in 76.3%
of cases, while 22.4% remained
unchanged and 1.3% worsened clinically
Schmidt A, et al J Am Coll Cardiol 2011;58:1105-9.
DEB BTK
• After 3 months an angiographical restenosis of
more than 50% was seen in 27.4% of all lesions
treated, with restenosis of the entire treated
segment of 9.5% (in the other cases of restenosis
of more than 50% only focal, short restenotic
lesions were seen)
• These data compare favourable to the data from
the same investigators in a similar group of 58
patients that were treated with non-coated
balloons: at 3 month angiographic follow-up
restenosis of more than 50% was seen in 69% of
cases, with restenosis of the whole treated
segment in 56% of cases
Schmidt A, et al J Am Coll Cardiol 2011;58:1105-9.
Conclusion
• DEB is a safe technology
• Even short‐term exposure to
paclitaxel‐coated balloon catheters is
sufficient to inhibit restenosis
• Results of DEB in animal studies and
coronaries as well as SFA/BTK are
promising
• Not all DEB’s are equal