- ACS - CK Naber, P Urban, PJ Ong, M Valdes-Chavarri, A Abizaid, SJ - - PowerPoint PPT Presentation

LEADERS FREE

• ACS -

CK Naber, P Urban, PJ Ong, M Valdes-Chavarri, A Abizaid, SJ Pocock, F Fabbiocchi, C Dubois, S Copt, S Greene and MC Morice for the LEADERS FREE Investigators

EuroPCR 2016

Conflicts of Interest

Christoph K Naber is shareholder of CERC, the CRO responsible for this trial

Background

LEADERS FREE ACS

• For ACS patients undergoing PCI current guidelines

recommend in general 12 months DAPT

• High bleeding risk patients presenting with ACS

undergoing PCI have never been systematically studied.

• Current guidelines recommend for these patients:
• I. Implantation of a DES with 3-6 months DAPT
• II. Implantation of a BMS with 1-month DAPT

Roffi et al. Eur Heart J. 2016;37:267-315 / Levine et al. JACC 2016 (epub ahead of print)

Objectives

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187: RESET: Kim BK et al, JACC 2012; 60: 1340 E-ZES 3 months DAPT 188: OPTIMIZE: Feres F et al, JAMA 2013; 310: 2510 E-ZES 3 months DAPT 189: EXCELLENT: Gwon HC et al, Circ 2012; 125: 505 DES 6 months DAPT 192: ISAR-SAFE: Schulz-Schupke S et al, EHJ 2015; 36: 1252 DES 6 months DAPT

Objectives

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The aim of this prespecified substudy was to evaluate the safety and efficacy of the BioFreedom™ BA9 DCS followed by 1 month DAPT in high bleeding risk patients presenting with an ACS

Drug Coated Stent (DCS)

BioFreedom™

Potential Advantages:

• Avoid any possible polymer-related adverse effects
• Rapid drug transfer to vessel wall (98% within one month2)
• Safe to shorten DAPT in High Bleeding Risk patients

1. Data on file at Biosensors Intl 2. Tada et al., Circ Cardiovasc Interv 2010;3;174-183

Trial Design

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Prospective, double-blind randomized (1:1) trial 2466 high bleeding risk (HBR) PCI patients

vs.

DAPT mandated for 1 month only, followed by long-term SAPT BioFreedom™ DCS Gazelle™ BMS

• Primary efficacy endpoint:

Clinically-driven TLR at 1 year (superiority)

• Primary safety endpoint:

Composite of cardiac death, MI, definite / probable stent thrombosis at 1 year (non-inferiority then superiority)

Urban P et al. Am Heart J 2013; 165: 704-9

Primary Endpoints

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Urban P et al. N Engl J Med 2015;373:2038-47

Efficacy (clinically driven TLR) Safety (cardiac death, MI, ST)

BMS DCS BMS DCS

Study Flow

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1 did not undergo PCI 2 did not undergo PCI 331 were assigned to BMS 331 were assigned to DCS 330 are include in the analysis* 329 are include in the analysis* 662 ACS patients underwent randomized 323 (97.8%) completed 12-month visit or died 320 (97.2%) completed 12-month visit or died

*N=659 (554 NSTEMI and 105 STEMI)

Study Population

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Parameter DCS (N=330) BMS (N=329) Total (N=659) p-value

Age (mean±SD) 76.9±10.0 76.5±9.0 76.7±9.5 n.s. Female N(%) 122 (37.0) 110 (33.4) 232 (35.3) n.s. NSTEMI N(%) 273 (82.8) 281 (85.5) 554 (84.1) n.s. STEMI N(%) 57 (17.2) 48 (14.5) 105 (15.9) n.s. Diabetes N(%) 111 (33.8) 108 (32.8) 219 (33.3) n.s. Renal Impairment N(%) 66 (20.1) 81 (24.8) 147 (22.4) n.s. Previous Stroke N(%) 46 (14.1) 26 (7.9) 72 (11.0) 0.01* Atrial Fibrillation N(%) 84 (25.5) 109 (33.1) 193 (29.3) 0.03* Previous MI N (%) 63 (19.1) 82 (24.9) 145 (22.0) n.s. Previous CABG N(%) 24 (7.3) 23 (7) 47 (7.1) n.s. Previous PCI N(%) 55 (16.7) 67 (20.4) 122 (18.5) n.s. *=Cox proportional hazard models displayed no influence on outcomes at FU

Criteria for High Risk of Bleeding*

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* There were no significant differences (P<0.05) between the two groups * n=1.8 per patient

2,1 1,2 1,6 1,8 3,6 5,8 4,6 11,2 10,9 24 24,3 30,7 69,6 2,1 1,2 1,8 1,2 4,2 5,5 7 10,6 11,5 22,1 18,8 23,9 70,6

10 20 30 40 50 60 70

Prior intracerebral bleed Severe chronic liver disease Stroke < 1 yr Thrombocytopenia* Glucocorticoids or NSAID ‡ Nonadherence to > 30d DAPT In hospital for bleeding < 1 year Cancer in previous 3 years Major surgery in the next year Hb < 11g/dl or TF < 4 weeks

• Creat. Clearance < 40 ml/min

Oral anticoagulation after PCI Age ≥ 75

DCS (N=330)2 BMS (N=329)

(%)

Procedural Data

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Parameter DCS (N=330) BMS (N=329) Total (N=659) p-value

Lesion Length mm (mean±SD) 18.3±11.3 17.6±8.9 17.9±10.1 n.s. Lesion Length ≥30 mm N(%) 33 (6.7) 40 (7.2) 73 (7.0) n.s. RVD mm (mean±SD) 3.0±0.5 3.0±0.5 3.0±0.5 n.s. RVD ≤2.75 mm (mean±SD) 166 (33.9) 167 (30.0) 333 (31.8) n.s. ACC-Class B2&C* N (%) 244 (30.6) 266 (29.5) 500 (30.0) n.s. LAD N/(%) 192 (58.2) 174 (52.9) 366 (55.5) n.s. Stent Length per patient (mm) (mean±SD) 33.4±23.3 36.5±26.5 35.0±25.0 n.s. Overlapping Stent N(%) 49 (14.8) 62 (18.9) 111 (16.9) n.s. Procedural Success N(%)** 326 (95.0) 341 (94.7) 667 (94.9) n.s. * Lesion Level; LL=Lesion Length; RVD=Reference Vessel Diameter; LAD=Left Anterior Descending; SD = Standard Deviation; **: includes all procedures (index and staged)

Clinically driven Target Lesion Revascularization - 12 Month FU

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9,0 3,9

1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10 11 12 13 Cumulative Incidence (%) Months

329 321 316 302 292 284 282 279 277 275 272 266 260 255 330 324 318 317 313 310 307 302 299 297 294 291 287 283

Primary Efficacy Endpoint HR 0.41: 95% Cl 0.21 to 0.82; p=0.009

Cardiac Death, MI, or Def / Prob ST- 12 Month FU

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18,5 9,3

2 4 6 8 10 12 14 16 18 20 1 2 3 4 5 6 7 8 9 10 11 12 13 Cumulative Incidence (%) Months

329 312 307 295 283 274 272 269 265 260 258 254 247 245 330 319 310 308 303 299 294 288 285 284 284 281 279 275

Primary Safety Endpoint HR 0.48: 95% Cl 0.31 to 0.75; p=0.001

12 Month Follow-up

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2 4 6 8 10 12 14 16

Death Cardiac death Myocardial infarction ST (Def/Prob) Bleeding (BARC 3-5)

DCS BMS

n.s. n.s. p=0.048 p=0.005 0.099

12 Month Follow-up by Subgroup

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Conclusions

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In ACS patients with high bleeding risk a polymer-free BA9- DCS combined with 1-month DAPT displays significantly better efficacy and safety than a BMS, the latter driven by significantly lower cardiac mortality and MI. Current guidelines should be reconsidered for high bleeding risk patients presenting with ACS: → BMS can no longer be recommended → Data on DES with shortened DAPT are scarce → BioFreedom™ BA9-DCS has strongest evidence in these patients.

LEADERS FREE ACS

Christoph K. Naber1, Philip Urban2, Paul J. Ong3, Mariano Valdes-Chavarri4, Alexandre

• A. Abizaid5, Stuart J. Pocock6, Franco Fabbiocchi7, Christophe Dubois8, Samuel Copt9,

Samantha Greene9, and Marie-Claude Morice10, for the LEADERS FREE Investigators

THANK YOU FOR YOUR TIME

BACKUP SLIDES

Medication

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Parameter DCS (N=330) BMS (N=329) p-value

UFH 282 (82.2) 280 (77.6) 0.12 LMWH 28 (8.2) 34 (9.4) 0.56 Bivalirudin 7 (2) 16 (4.4) 0.07 GPIIbIIIa antagonist 7 (2) 5 (1.4) 0.50 DAPT at day 23 317 (97.8) 311 (95.7) 0.18 DAPT at day 37 28 (8.7) 49 (15.2) 0.01* In LEADERS FREE 659/2466 patients had an ACS (554 NSTEMI and 105 STEMI) *=Cox proportional hazard models displayed no influence on outcomes at FU

Stratification of MI at 12-Month Follow-up

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Given that many patients di not undergo control angiography when readmitted during follow-up, a definite distinction between Types I, 4b and 4c was sometimes difficult to establish.