The Valentines II Trial Dr. Antonio Serra

Barcelona, Spain

On Behalf of the

Valentines II Trial Investigators

Background Drug eluting balloons (DEB) are emerging as a potential

alternative to combat restenosis.

The DEB technology demonstrated safety and efficacy in randomized clinical trials for patients with in-stent restenosis.

The question now is whether DEB as adjunct therapy to POBA can be a viable alternative to stenting in patients with “de novo” lesions in native coronary arteries.

Aim of the Study To assess safety and efficacy of the paclitaxel-eluting balloon Dior® treatment of “de novo” lesions at 6-9 months follow-up.

PRIMARY END-POINT: Clinical Outcomes (MACE):

– Death

– Myocardial infarction

– Target lesion revascularization (TLR)

– Target vessel revascularization (TVR)

– Vessel thrombosis (both early and late occurrences)

Cohort analysis with angiographic follow-up

– Late Loss

– Binary Restenosis

Methods • Multi-center, International, Short-term Valentines-

Registry

• Goal of up to 150 patients recruited at up to 50 centers

• Enrollment from 14 Feb 2011 – 31 March 2011

• Elective PCI for treatment of “de novo” lesions in native vessels with DEB (DIOR ®), with adjunctive angioplasty.

• Clinical follow up and angiographic cohort analysis at 6-9 months

Inclusion Criteria Patients over the age of 18

Clinical presentation

Stable or unstable angina, and/or evidence of ischemia.

Angiographic criteria

“de novo” lesion(s) in the native coronary system.

Up to two lesions per patient

Target lesion stenosis is > 50%

Exclusion Criteria Acute MI < 48 hours

Lesions in the Left main coronary artery

Lesion length > 24mm (longest DIOR 30 mm)

Heavily calcified, thrombotic & bifurcation lesions.

Lesion requiring additional stenting with either BMS or DES prior to the DEB treatment.

Co-morbid illnesses likely to limit life expectancy to less than 12 months.

Enrollment

38 Investigators

Africa: 1

Asia: 24

Europe: 53

South America: 25

From 16 Countries

122 CRF

102 with follow up Mean: 227 ± 40 days

103 patients

1 patient

lost to follow up

19 Patients Excluded 13 Inclusion/ Exclusion Criteria

6 Unanswered Procedural Queries

99.0%

Follow up 50.5% On-site

Clinical Monitoring

Baseline Demographics (n=103)

Male 79.6%

Age (years) 62.6 ± 10.2

Previous MI 27.2%

Previous CABG 6.8%

Diabetes Mellitus 28.2%

- Insulin Dependent Diabetes Mellitus 7.8%

Smoking 35.9%

Hyperlipidemia 59.2%

Hypertension 83.5%

Renal Insufficiency 1.0%

Peripheral Vascular Disease 7.8%

Clinical Presentation (n=103)

Stable Angina 41.7%

Unstable Angina 38.8%

Positive Functional Test 19.4%

Left Ventricular Ejection Fraction 55.4 ± 10.8%

Baseline Lesion Characteristics

N = 103 patients / 109 lesions

Number of lesions per patient 1.06 ± 0.24

% stenosis (visual estimate) 83.3 ± 9.5

Treated vessel : - LCx 38.3%

- LAD 34.0%

- RCA 27.7%

Lesion Location :

Ostial 4.3% Prox 32% Mid 32% Distal 29%

Procedural Details (n=109 lesions)

Pre-dilatation (POBA / Cutting) 85% / 1%

% stenosis after pre-dilatation 21.3+15.8

DIOR Balloons per lesion 1.04 ± 0.19

- Balloon Diameter (mm) 2.7 ± 0.4

- Balloon Covered Length (mm) 20.4 ± 5.1

- Maximum Inflation Pressure (atm) 10.8 ± 3.5

- Total Balloon Inflation time (seconds) 71.3 ± 32.4

Post DEB dilatation 3.7%

Procedural results (n=109 lesions)

Coronary Dissection (n=16) 14.7%

- Abrupt Closure (n=1) 0.9%

Failure (dissection + residual stenosis) n=1 0.9%

Stent Implantation “Bailout” (n=13) 11.9%

% final stenosis 10.4 ± 10.6

Device Success (DIOR strategy) 87.2%

Procedural Success / patient (1 failure) 99.0%

Procedural Results

10

1 1 1

In Hospital Outcomes

(n=103)

%

Bailout stenting with MACE: 1 pt

Length of stay 3.8 + 3.5 days

Clinical Follow-up Outcomes

(n=102)

Mean Follow up was 227 ± 40 days

MACE is defined as, all cause death, MI, TVR and Vessel Thrombosis

%

Snapshot Angiographic Follow-up (n=26)

Baseline

Reference Vessel Diameter (mm) 2.3 ± 0.4

Pre Diameter Stenosis % 64.2 ± 14.9

Pre MLD (mm) 0.8 ± 0.4

Lesion length (mm) 10.2 ± 5.2

DEB Segment Analysis

Final Diameter Stenosis % 21.6 ± 7.8

Final MLD (mm) 1.8 ± 0.3

Follow-up Diameter Stenosis % 32.9 ± 18.0

Follow up MLD (mm) 1.5 ± 0.5

Late Lumen Loss (mm) 0.30 ± 0.36

Binary Restenosis (≥ 50%) 3 (10.7%)

Overall DM vs. Non-DM

%

0

2

4

6

8

10

12

14

16

MACE Death Cardiac

Death

MI Vessel

Thrombosis

TLR TLR + TVR

DM

Non-DM

Clinical Follow up Outcomes

Mean Follow up was 230 ± 43 vs. 226 ± 39 days in the DM and Non-DM groups , respectively. MACE is defined as, all cause death, MI, TVR and Vessel Thrombosis

100% follow up DM

98.6% follow-up non DM

%

13.8

6.8

0

1.4

0 0

1.4

0 0 0

6.9

1.4

13.8

4.1

Male, 65 yrs old

HTA, dyslipidemia

Stable angina, class II

SPECT + lateral wall

90% stenosis marginal branch

Case 1

6 months follow-up. After POBA + DIOR

Male, 71 yrs old

Smoker, HTA

Progressive angina

Anterior ischemia

85% ostial LAD

Case 2

Post-Cutting Cutting Balloon

Post-DIOR DIOR Balloon

Post-DIOR 6 months follow-up

Summary This web-based, CRT conference associated trial collected data of

103 patients from 16 countries and 38 investigators.

Patient were enrolled over a month and a half.

The treatment of “de novo” lesions with the DIOR® Balloon is

safe. There was an acceptable rate of bailout stenting due to

intra-procedural complications (11.9% in lesion).

The DIOR® DEB treatment overall has a TLR rate of 2.9% and a

TVR rate of 6.9% at 6-9 months follow-up.

• In Non-DM patients TLR rate is 1.4% and TVR rate 4.1%.

• In DM patients TLR rate is 6.9% and TVR rate 13.8%.

Summary The preliminary late loss upon angiographic follow up of a small

subset of patients was 0.30 ± 0.36mm for the DEB segment

analysis.

The results obtained in The Valentines II trial are similar to those

observed in the Spanish Registry for Small Vessels :

- 103 patients

- Reference vessel diameter 1.9 + 0.3 mm

- MACE 5.8% and TLR 2.9% at 12 months

- Late loss 0.34 + 0.23 mm (50% angio follow-up)

Conclusions

The DIOR ® DEB system when used for de novo lesions demonstrated safety (2% death / MI) and efficacy (6.9% TLR + TVR) at 9 m follow-up.

Further investigations with the use of the DIOR DEB system is required to establish the role of this technology for de novo lesions.

Thank You!! Principle Investigators

F. Malik A. Rodriguez A. Serra

Local Investigators Yu Lievano Gaspar

Sgueglia Draganov Vargas

Petrovski Chin Zverev

Von Korn Shivkumar Sheiban

Denchev Menown Vijayvergia

Grinfeld Garcia Mithrakumar

Demin Ganiukov Trehan

Vaquerizo Bettinotti Asadulaev

Auer Goldsmit Schloido

Merkely Osiev Marouen

Utech Larionov Urdiales

Ismail Sahnoun Goyal