Drug eluting balloons in CAD

Transcription

1 Drug eluting balloons in CAD Ioannis Iakovou, MD, PhD Interventional Cardiology 1 st Cath Lab Onassis Cardiac Surgery Center

2 Drug-Eluting Balloons (DEB) Technology and Applications 1. Special Features and Technology 2. Appropriate Technique to use a DEB 3. Historical Clinical Studies 4. Clinical Pivotal Studies with CE-certified DEB 5. Guideline-Recommended Applications 6. Possible Applications beyond the Guidelines

3 Drug-Eluting Balloons (DEB) Technology and Applications 1. Special Features and Technology 2. Appropriate Technique to use a DEB 3. Historical Clinical Studies 4. Guideline-Recommended Applications 5. Clinical Pivotal Studies with CE-certified DEB 6. Possible Applications beyond the Guidelines

4 DEB Challenges as compared to DES DEB DES Drug Delivery Platform balloon stent scaffold Drug Retention embedded in an excipient polymer Drug (usually) Paclitaxel many different high low Dose µg < µg Release Kinetics fast slow Drug Distribution homogenous from balloon surface inhomogenous from stent struts

5 Second Generation of DEB

6 Second Generation of DEB

7 Drug-Eluting Balloons (DEB) Technology and Applications 1. Special Features and Technology 2. Appropriate Technique to use a DEB 3. Historical Clinical Studies 4. Clinical Pivotal Studies with CE-certified DEB 5. Guideline-Recommended Applications 6. Possible Applications beyond the Guidelines

8 Appropriate Technique to use a Drug-Eluting Balloon (DEB) The DEB is not a balloon for angioplasty!

9 Appropriate Technique to use a Drug-Eluting Balloon (DEB) The DEB is not a balloon for angioplasty! The DEB is a system to deliver a drug into the arterial wall

10 Appropriate Technique to use a Drug-Eluting Balloon (DEB) 1. Step one: dilate the stenosis with an angioplasty balloon (if the lesion is in-stent restenosis, prefer a cutting or scoring balloon to avoid slipping-induced vessel trauma to adjacent segments)

11 Appropriate Technique to use a Drug-Eluting Balloon (DEB) 1. Step one: dilate the stenosis with an angioplasty balloon (if the lesion is in-stent restenosis, prefer a cutting or scoring balloon to avoid slipping-induced vessel trauma to adjacent segments). 2. Step two: try to obtain a stent-like result with angioplasty alone.

12 Appropriate Technique to use a Drug-Eluting Balloon (DEB) 1. Step one: dilate the stenosis with an angioplasty balloon (if the lesion is in-stent restenosis, prefer a cutting or scoring balloon to avoid slipping-induced vessel trauma to adjacent segments) 2. Step two: try to obtain a stent-like result with angioplasty alone 3. Step three: choose a DEB somewhat longer than the angioplasty balloon to avoid geographical miss.

13 Appropriate Technique to use a Drug-Eluting Balloon (DEB) 1. Step one: dilate the stenosis with an angioplasty balloon (if the lesion is in-stent restenosis, prefer a cutting or scoring balloon to avoid slipping-induced vessel trauma to adjacent segments) 2. Step two: try to obtain a stent-like result with angioplasty alone 3. Step three: choose a DEB somewhat longer then the angioplasty balloon to avoid geographical miss. 4. Step four: inflate the DEB with the nominal pressure for the recommended inflation time. Adapted from S.Silber

14 Drug-Eluting Balloons (DEB) Technology and Applications 1. Special Features and Technology 2. Appropriate Technique to use a DEB 3. Historical Clinical Studies 4. Clinical Pivotal Studies with CE-certified DEB 5. Guideline-Recommended Applications 6. Possible Applications beyond the Guidelines

15 PACCOCATH-ISR I and II: coat ed Paccocath was a Prototype DEB, not commercially available

16 Drug-Eluting Balloons (DEB) Technology and Applications 1. Special Features and Technology 2. Appropriate Technique to use a DEB 3. Historical Clinical Studies 4. Clinical Pivotal Studies with CE-certified DEB 5. Guideline-Recommended Applications 6. Possible Applications beyond the Guidelines

17 Drug-eluting Balloons (DEB) for In-Stent Restenosis after Bare Metal Stents (BMS) or Drug-eluting Stents (DES) Product* Excipient Company Study DIOR-II Shellac EuroCor VALENTINES-I In.Pact Falcon Urea Medtronic Registry Pantera Lux BTHC Biotronik PEPPER DELUX SeQuent Please Iopromide B Braun PEPCAD-II SES-ISR Danubio BTHC Minvasys Registry

18 Drug-eluting Balloons (DEB) for In-Stent Restenosis after Bare Metal Stents (BMS) or Drug-eluting Stents (DES) Product* Study Time of TLR TLR BMS-ISR DIOR-II VALENTINES-I 9 months 5.1 % (of 157 pats) TLR DES-ISR 10.8 % (of 83 pats) In.Pact Falcon Pantera Lux Registry 6 months 4.3 % (of 26 pats) PEPPER 12 months 2.4 % (of 41 pats) 17.1 % (of 35 pats) DELUX 6 months 2.0 % (of 277 pats ) 6.6 % (of 248 pats) SeQuent Please PEPCAD-II SES-ISR WWR 12 months 6 months 9 months 6.3 % (of 66 pats) 3.8 % (of 730 pats) 4.3 % (of 25 pats) 9.6 % (of 457pats)

19 Treatment of DES ISR- PEPCAD-DES study

20 Treatment of DES ISR-PEPCAD-DES study 110 patients with DES ISR located in a native coronary artery to paclitaxel-coated balloon angioplasty or uncoated balloon angioplasty

21 Treatment of DES ISR- PEPCAD-DES study clinical 6 mos

22 ISAR-DESIRE 3: Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis: 3 Treatment Approaches Design 402 patients with DES-restenosis enrolled between August 2009 and October 2011 in 3 centers in Germany PRIMARY ENDPOINT: Percent diameter stenosis at followup angiography TEST HYPOTHESES: PEB non-inferior to PES %DS 35%; Delta = 7% alpha = 0.05; Power = 80% 102 Patients/group PEB and PES superior to balloon angioplasty %DS 35% vs. 45% alpha = 0.025; Power 90% 101 Patients/group Paclitaxeleluting balloon (SeQuent) (N=137) Paclitaxeleluting stent (Taxus) (N=131) Angiographic follow-up at 6-8 months in 84.1% (N=338) Balloon angioplasty alone (N=134) Clinical follow-up at 12 months in 97.5% (N=392) No significant differences across groups

23 Cumulative Frequency (%) ISAR-DESIRE 3: Primary Endpoint Diameter Stenosis at Follow-up Angiography Paclitaxel-Eluting Balloon (PEB) Paclitaxel-Eluting Stent (PES) Balloon Angioplasty (BA) PEB 38.0% PES 37.4% PEB versus BA PES versus BA P superiority < PEB versus PES P non-inferiority =0.007 BA 54.1% Diameter Stenosis at Follow-up Angiography (%) ISAR-DESIRE 3: Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis: 3 Treatment Approaches

24 Inclusion Criteria Informed Consent RIBS IV (Januray 2010 August 2013) 309 Pts DES-ISR Randomization Rx Centralized Stratification: ISR Length & Edge Xience Prime (Abbott Vascular) 4 Died 18 Refused Mean: 279 days (Median: 248) 155 Pts EES 133 Pts Angio FU 100% Angiographic Success QCA Primary End-point 154 Pts DEB 139 Pts Angio FU (272 Patients: 90% of Eligible) SeQuent Please (B. Braun) 3 Died 12 Refused Mean: 266 days (Median: 246)

25 RIBS IV Cumulative Frequency Distribution Curves The primary endpoint of the study is minimal lumen diameter at angiographic follow-up 100 (%) POST p < RE 15 (11%) 27 (19%) p = 0.06 RR (95%CI) 1.44 ( ) PRE FU p = EES DEB In-Segment (%) Stenosis Intention to Treat

26 Drug-Eluting Balloons (DEB) Technology and Applications 1. Special Features and Technology 2. Appropriate Technique to use a DEB 3. Historical Clinical Studies 4. Clinical Pivotal Studies with CE-certified DEB 5. Guideline-Recommended Applications 6. Possible Applications beyond the Guidelines

27 EHJ, 31: , (2010)

28 Procedural aspects of PCI Specific PCI devices *Recommendations are only valid for specific devices with proven efficacy/safety profile, according to the respective lesion characteristics of the studies.

29 ESC 2014 revasc guidelines

30 Drug-Eluting Balloons (DEB) Technology and Applications 1. Special Features and Technology 2. Appropriate Technique to use a DEB 3. Historical Clinical Studies 4. Guideline-Recommended Applications 5. Clinical Pivotal Studies with CE-certified DEB 6. Possible Applications beyond the Guidelines

31 PCI of Small vessels

32 DCB in Bifurcations: database overview World Wide Registry (13 %, no specific report so far) Small Vessel Registry (23 %, no specific report so far) Australian Jepsen report 2013 mainly ISR PEPCAD V (MB stenting SB provisional stenting) (DCB only in-segment LLL 0.04mm) Sgueglia 2011(MB stenting, kissings DEBs) Herrador 2013 (MB DES, SB DCB & provisional stenting) Kenneth Chin 2013 (DES MB, DCB SB) Biolux-I (DES MB, DCB SB) - Schulz 2013 (DEB only) - Debiut Study (only randomized study, MB stenting SB provisional stenting, Paclitaxel without matrix/excipient)

33 DEBIUT randomized trial Discussion DEBIUT Results at 6 months DES Group DEB Group main branch side branch main branch side branch Ref. Diameter (mm): 2.8 / / Restenosis Rate (%): (in-segment) 5.4 / / TVR (%): Stent Thrombosis (%): Dual Antiplatelet Therapy (months): 12 3

34 DEB for DES ISR involving true bifurcation 52 y, male, smoker, hypertensive with prior PCI LAD (DES) a year ago presenting with UA.

35 DEB for DES ISR involving true bifurcation 2 wires (whisper, Prowater) Ivus (Atlantis Pro) Stent underexpansion and focal restenosis

36 DEB for DES ISR involving true bifurcation Balloon predilataions: 1.SB Sprinter 2.0x 10 (16 Atm) 2.MB NC 3.0 x 12 (16 atm) 3.Dior 3.0 x 15 (12 Atm) 4.FKB (2& 3)

37 Angio Post FKB

38 IVUS findings Csa=9.05 mm 2 Csa=7.2 mm 2 Csa=8.06 mm year FU pt is asymptomatic with negative EST & Tl-201

39 Take Home Message: 1. Drug-eluting balloons are a real innovation in interventional cardiology. 2. The use of a DEB must follow specific standards. 3. Several DEB have provided clinical data for ISR after BMS and DES. They seem to have a single digit number of TLR rates within the first 9 to 12 months after PCI of BMS-ISR. 4. The TLR rates after PCI of DES-ISR seem to be generally higher. 5. The ESC guidelines recommend DEB only for in-stent restenosis. 6. Possible additional indications are sidebranches of bifurcation lesions and de-novo lesions in small vessels to avoid unnecessary implantation of permanent metal. Drug-Eluting Balloons (DEB) Technology and Applications 7. Trials with a primary clinical endpoint are needed.