The RIBS IV Clinical Trial

Transcription

1 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 Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company None None

3 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 1 st Generation DES However, the value of DEB compared with 2 nd Generation DES in patients with DES-ISR remains unknown

4 Objective: We sought to compare the efficacy of DEB vs EES in patients with DES-ISR

5 RIBS IV: (Restenosis Intra-stent: DEB vs EES) Multicenter, Prospective, Randomized 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. 1.- CORUÑA H U Juan Canalejo 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 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. 2.- VALENCIA H U Clínico VALENCIA H U General VIGO H U Meixoeiro 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

6 RIBS IV: (Restenosis Intra-stent: DEB vs EES) Multicenter, Prospective, Randomized Coordinating Center: Hospital Universitario Clínico San Carlos. Madrid. Steering Committee: F. Alfonso (Chairman and Principal Investigator), J. Zueco, A. Cequier, C. Morís, C. Macaya. Clinical Events Committee: R. Hernández, M. Sabaté. Coronary Angiography Core Laboratory: (Hospital Universitario Clinico San Carlos, Madrid) A. Cárdenas, M.J. Pérez-Vizcayno. Data Coordination, Safety Monitoring and Statistical Committee: M.J. Pérez-Vizcayno, C. Fernández. Intravascular Ultrasound and Optical Coherence Tomography Committee: N. Gonzalo, F. Alfonso. Sites and Investigators: In order of enrollment: 1 Hospital Universitario Clínico San Carlos, Madrid, (P. Jiménez-Quevedo, N. Gonzalo, J. Escaned, A. Fernández-Ortiz, C. Macaya); 2 Hospital Universitario Vall d Hebron, Barcelona, (B. García del Blanco); 3 Hospital Universitario Puerta de Hierro, Majadahonda, (A. García-Touchard); 4 Hospital Universitario Infanta Cristina. Badajoz, Badajoz, (J.R. López-Mínguez); 5 Hospital Universitario de la Princesa, Madrid, (F Alfonso, A Benedicto.); 6 Hospital Universitario Clinic de Barcelona, Barcelona, (M. Masotti); 7 Hospital Universitario Marqués de Valdecilla, Santander, (J. Zueco); 8 Complejo Hospitalario Universitario de Vigo, Vigo, (A. Iñiguez); 9 Hospital Universitario 12 de Octubre, Madrid, (T. Velazquez); 1 Hospital Universitario General de Valencia, Valencia, (F. Pomar); 11 Hospital Universitario de Alicante, Alicante, (V. Mainar); 12 Hospital Universitario La Paz, Madrid, (R. Moreno); 13 Hospital Universitario Virgen de la Victoria, Málaga, (J.M. Hernández); 14 Hospital Universitario Virgen de las Nieves, Granada, (R. Melgares); 15 Hospital Universitario de Bellvitge, Barcelona, (A. Cequier); 16 Hospital Universitario Sant Pau, Barcelona, (V. Martí); 17 Hospital Universitario Son Espases, Palma de Mallorca, (A. Bethecourt); 18 Hospital Universitario Virgen de la Salud Toledo, Toledo, (J. Moreu); 19 Hospitalario Universitario Central de Asturias, Oviedo, (C. Morís); 2 Hospital Universitario Clínico de Valencia, Valencia, (J. Sanchís); 21 Hospital Universitario Carlos Haya, Malaga, (C.A. Urbano-Carrillo); 22 Hospital Universitario Miguel Servet, Zaragoza; (M.C. Ferrer-Gracia); 23 Complejo Hospitalario Universitario Juan Canalejo, La Coruña, (N. Vázquez).

7 Inclusion / Exclusion Criteria Inclusion: Informed consent Age 2-85 y DES ISR (> 5% stenosis) Angina or silent ischemia ISR amenable for BA & Stent Exclusion: Stent Related: Stent location undefined ISR <1 Month Thrombus Vessel diameter < 2 mm ISR length > 3 mm ISR outside the Stent General: Life expectancy < 1 y Female in childbearing age Problems FU angiography Intolerance ASA/Clopidogrel LVEF < 25%

8 Sample Size Calculation EES After Stent implantation: MLD = 2.6 mm RIBS I and RIBS II (1,2) Late loss:.6 mm (.4 mm ISAR-DESIRE-2 (3) ) MLD at FU: mm DEB After Balloon dilation: MLD = 2.2 mm RIBS I and RIBS II (1,2) Late loss:.4 mm (.4 mm ELL (4) ;.37 ISAR-DESIRE-3 (5) ) MLD at FU: ~ 284 Pts (142 per arm) (power 8%, alpha error 5%) ~ 31 Pts (155 per arm) assuming a drop-out rate ~1% 1. Alfonso F. J Am Coll Cardiol 23;42: Alfonso F. J Am Coll Cardiol. 26;47: Mehilli J. J Am Coll Cardiol. 21;55: Alfonso F. Am Heart J.25;149:e Byrne RA. Lancet.213;381:461-7 (published after RIBS IV trial was designed) At initial trial design little evidence on DES-ISR results: «worst-case scenario calculation»

9 Inclusion Criteria Informed Consent RIBS IV (Januray 21 August 213) 39 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 1% Angiographic Success QCA Primary End-point 154 Pts DEB 139 Pts Angio FU (272 Patients: 9% of Eligible) SeQuent Please (B. Braun) 3 Died 12 Refused Mean: 266 days (Median: 246)

10 Clinical Data (I) All (N 39) EES (N 155) DEB (N 154) Age (years) Female 52 (17) 25 (16) 27 (18) Risk Factors Diabetes 141 (46) 66 (43) 75 (49) Hyperlipidemia 231 (75) 121 (78) 11 (71) Hypertension 231 (75) 121 (78) 11 (71) Ever smoked 176 (57) 87 (56) 89 (58) Family history 18 (6) 9 (6) 9 (6)

11 Clinical Data (II) All (N 39) EES (N 155) DEB (N 154) Previous History Myocardial infarction 15 (49) 77 (5) 73 (47) Bypass surgery 33 (11) 17 (11) 16 (1) Clinical Features Unstable angina 159 (52) 79 (51) 8 (52) Stable angina/silent I 15 (48) 76 (49) 74 (48) Time to ISR (days) 547 ( ) 55 ( ) 52 ( )

12 Angiographic Data (I) All (N 39) EES (N 155) DEB (N 154) Target Vessel : LAD 148 (48) 71 (46) 77 (5) RCA 88 (28) 45 (29) 43 (28) LCX 61 (2) 34 (22) 27 (18) SVG 12 (4) 5 (3) 7 (4) LVEF (%) # Diseased Vessels

13 Procedural Data All (N 39) EES (N 155) DEB (N 154) Initial Stent: Length of initial stent (mm) Maximal pressure (atm) Index Procedure (RIBS): Maximal pressure (atm) * Maximal balloon diam (mm) EES / DEB length (mm) Total inflation time (sec) 9 (45-12) 45 (3-73) 95 (9-12)* Cross-over 6 (2) 1 (.6) 5 (3) * p<.1

14 3 2,5 2 1,5 1,5 QCA: In-Segment Analysis Reference Diameter Lesion Length (mm) p =. 21 RIBS IV (mm) p =.56 EES DEB CAAS II System

15 QCA: MLD at FU 2,5 MLD-FU (mm) EES DEB p =.4 Seg Lesion 2 1,5 1,5 2, In-Segment (Primary Endpoint) MLD-FU (mm) p <.1 2 1, ,5 In-Lesion

16 Cumulative Frequency Distribution Curves 1 (%) 8 6 PRE FU p =.4 POST p = EES DEB In-Segment MLD (mm) Intention to Treat

17 Cumulative Frequency Distribution Curves 1 (%) 8 6 POST p <.1 RE 15 (11%) 27 (19%) p =.6 RR (95%CI) 1.44 ( ) PRE 4 2 FU p =.9 EES DEB In-Segment (%) Stenosis Intention to Treat

18 All Age >65y Female Diabetes UA Time RE (< 6Mo) LAD Vessel QCA (< 3mm) RE Length (>1mm) Edge ISR B/A > 1.1 * AMD= Absolute Mean Difference 1 Pre-Specified Variables: (272) (147) (44) (124) (133) (26) (128) (22) (111) (66) (179) DEB Better RIBS IV MLD FU EES Better AMD * P Value All interactions (NS)

19 In-Segment Analysis (QCA) Late Loss vs.3+.6 mm 2 1 4, (mm) EES DEB ,, 1, 2, 3, 4, 3, (-.2.4) ( ) Kolmogorov-Smirnov <.5 2, *p = ,, 1-1, -1,, 1, 2, 3, 4, * median (IQR); Mann-Whitney U

20 6 RIBS IV Events at Final FU (1 Year) 1 Year FU 39 P (1%); FU Time days Thrombosis ARC EES DEB # 1 1 ç 1 & 1 # Definitive (3) Probable (2) Possible (3) + After TLR with DES ç Discontinuation DAT Subdural hematoma & STEMI related # Cardiac death FU Intention to Treat

21 Clinical Follow-up: 1 Year FU 39 P (1%); FU Time days 1 % 96% Breslow, p =.8 Log Rank, p =.8 EES DEB 87% 2 Freedom from TLR Time (months)

22 Clinical Follow-up: 1 Year FU 39 P (1%); FU Time days 1 % 9% Breslow, p =.47 Log Rank, p =.44 EES DEB 82% 2 Freedom from MACE (Cardiac Death, MI, TVR) Time (months)

23 DEB vs BA in the RIBS Trials 2,5 2 (mm) MLD FU p < ,9,8,7 (mm) Late Loss p <.5 1, ,6,5 1,4,3.3+.6,5, ,1 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

24 Conclusions: In patients with DES-ISR EES provide superior late angiographic results than DEB (MLD 1 ry 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.