1. The RIBS IV Clinical Trial
A Prospective, Randomized Trial of Paclitaxel-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With Coronary In-Stent Restenosis of Drug-Eluting Stents:
The RIBS IV Clinical Trial
Fernando Alfonso MD, PhD, FESC
Hospital Universitario “La Princesa” Madrid. Spain
On Behalf of the RIBS IV Investigators

2. All faculty disclosures are available on the CRF Events App and online at www.crf.org/tct

3. RIBS IV
Background:
Treatment of patients with DES-ISR remains a challenge
In this setting, DES provide better results than classical coronary interventions.
Drug-eluting balloons (DEB) are also very effective in patients with BMS-ISR and DES-ISR, with results superior to those obtained by conventional BA and equivalent to those seen with 1st Generation DES
However, the value of DEB compared with 2nd Generation DES in patients with DES-ISR remains unknown

4. Investigators´ Driven Initiative B. Braun & Abbott Vascular
RIBS IV
RIBS IV: (Restenosis Intra-stent: DEB vs EES)
Multicenter, Prospective, Randomized 23 4 3 1 17 18 2 8 5 6 7 9 10 11 13 12 15 16 14 21 20 22 19
1.- ALICANTE H U General. 2.- ASTURIAS H U Central Asturias.
3.- BADAJOZ H U Infanta Cristina. 4.- BALEARES H U Son Espases.  5.- BARCELONA H U Bellvitge. 6.- BARCELONA H U Clínico. 7.- BARCELONA H U Santa Cruz y San Pablo. 8.- BARCELONA H U Valle de Hebrón. 9.- CANTABRIA H U Marqués de Valdecilla CORUÑA H U Juan Canalejo.  11.- GRANADA H U Virgen de las Nieves MADRID H U Doce de Octubre MADRID H U La Paz MADRID H U La Princesa MADRID H U Puerta de Hierro.  16.- MADRID H U Clínico San Carlos MALAGA H U Carlos Haya MALAGA H U Virgen de la Victoria. 19. TOLEDO H U Virgen de la Salud Toledo.
20.- VALENCIA H U Clínico VALENCIA H U General  VIGO H U Meixoeiro.
23.- ZARAGOZA H U Miguel Servet.
Steering Committee. QCA & Clinical Events Committee
Under the Auspices PCI WG Spanish Society of Cardiology
Coordinator Center: HU Clínico San Carlos. Madrid.
Investigators´ Driven Initiative
Unrestricted Grants:
B. Braun & Abbott Vascular

5. Inclusion / Exclusion Criteria
RIBS IV
Inclusion / Exclusion Criteria
Inclusion:
Exclusion:
Stent Related:
Stent location undefined
ISR <1 Month
Thrombus
Vessel diameter < 2 mm
ISR length > 30 mm
ISR outside the Stent
General:
Life expectancy < 1 y
Female in childbearing age
Problems FU angiography
Intolerance ASA/Clopidogrel
LVEF < 25%
Informed consent
Age y
DES ISR (> 50% stenosis)
Angina or silent ischemia
ISR amenable for BA & Stent

6. 100% Angiographic Success
RIBS IV
(Januray 2010 – August 2013)
Rx Centralized
Stratification:
ISR Length & Edge
Inclusion Criteria
Informed Consent
309 Pts DES-ISR
Randomization
155 Pts
154 Pts
Xience Prime
(Abbott Vascular)
SeQuent Please
(B. Braun)
EES
DEB
100% Angiographic Success
4 Died
18 Refused
3 Died
12 Refused
133 Pts
139 Pts
QCA
Angio FU
Primary End-point
Angio FU
Mean: 279 days
(Median: 248)
Mean: 266 days
(Median: 246)
(272 Patients: 90% of Eligible)

7. QCA: In-Segment Analysis
RIBS IV
QCA: In-Segment Analysis
Reference Diameter
Lesion Length
(mm)
(mm)
10.7+5
10.4+6
p = 0. 21
p = 0.56
DEB
EES
CAAS II System

8. QCA: In-Segment Analysis
RIBS IV
QCA: In-Segment Analysis
DEB
EES
MLD-FU
(mm)
p = 0.004
2.03
In-Segment
(Primary Endpoint)
1.80
Seg
Lesion
MLD-FU
(mm)
p <
2.20
1.89
In-Lesion

9. __ RIBS IV (%) Stenosis Cumulative Frequency Distribution Curves (%)
15 (11%)
27 (19%)
p = 0.06
RR (95%CI) 1.44 ( )
POST
PRE
p < 0.001 FU
p = 0.009 __
DEB
EES
(%) Stenosis
In-Segment
Intention to Treat

10. In-Segment Analysis (QCA)
RIBS IV
In-Segment Analysis (QCA)
Late Loss
4,00
3,00
2,00
1,00
0,00
-1,00 30 20 10
DEB
EES
vs mm
(mm)
0.06
0.14
4,00
(-0.20 – 0.40)
(-0.18 – 0.65)
3,00
Kolmogorov-Smirnov <0.05
2,00
*p = 0.06
4,00
3,00
2,00
1,00
0,00
-1,00 30 20 10
1,00
0,00
-1,00
* median (IQR); Mann-Whitney “U”

11. Events at Final FU (1 Year)
RIBS IV
Events at Final FU (1 Year)
1 Year FU 309 P (100%); FU Time days
MACE (Cardiac Death, MI, TLR): Non-exclusive 19
MACE (Exclusive)
p = 0.009
HR 0.39 (95%CI )
EES: 10 (7%)
DEB: 24 (16%) 6 5 2 2 2 1 1
C Death (4)
AMI (7)+
CABG TLR (2)
PCI TLR (25)
+ 3 Definitive ST Thrombosis (1 EES y 2 DEB [all after re-PCI & stenting])
Intention to Treat

12. __ Clinical Follow-up: 96% 87% RIBS IV EES DEB Freedom from TLR
1 Year FU 309 P (100%); FU Time days %
96%
100 80
87%
Breslow, p = 0.008
Log Rank, p = 0.008 __
EES
DEB 60 40 20
Freedom from TLR 1 2 3 4 5 6 7 8 9 10 11 12
Time (months)

13. __ Clinical Follow-up: 90% 82% RIBS IV EES DEB
1 Year FU 309 P (100%); FU Time days %
90%
100 80
82%
Breslow, p = 0.047
Log Rank, p = 0.044 __
EES
DEB 60 40 20
Freedom from MACE (Cardiac Death, MI, TVR) 1 2 3 4 5 6 7 8 9 10 11 12
Time (months)

14. DEB vs BA in the RIBS Trials
RIBS IV
DEB vs BA in the RIBS Trials
MLD FU
Late Loss
(mm)
(mm)
p < 0.01
p < 0.05
BA RIBS I
BA RIBS II
DEB RIBS V
DEB RIBS IV
BA RIBS I
BA RIBS II
DEB RIBS V
DEB RIBS IV
BMS-ISR
DES-ISR
BMS-ISR
DES-ISR
(QCA) In-Segment Analysis

15. RIBS IV
Conclusions:
In patients with DES-ISR EES provide superior late angiographic results than DEB (MLD 1ry end-point)
In these patients EES also provide better late clinical results, driven by a significant reduction in the rate of TLR
Treatment of DES-ISR remains challenging and associated with poorer clinical and angiographic results than treatment of BMS-ISR. Further studies (more patients & longer follow-up) are still warranted in this adverse setting.