Bifurcation and Stent Thrombosis “Debriefing”

1. Bernard De Bruyne, MD, PhD Cardiovascular Centre, Aalst www.cardio-aalst.be bernard.de.bruyne@olvz-aalst.be Bifurcation and Stent Thrombosis“Debriefing” Chair C. Rouguelov, F. Perreira Machado, G. Stankovic Bifurcation stent is a predictor of stent thrombosis? BK Koo Is there a biological problem ? S Hoffamn VASP guided LM stenting ? O Darremont Can we decrease stent thrombosis in bifurcation ? B De Bruyne

2. Everything you always wanted to know aboutBifurcation and Stent Thrombosisbut were afraid to ask • What we know • What we thought we knew • What we don’t know • What we would like to know

3. Bifurcation and Stent Thrombosis What we know • Bifurcation stenting is technically more challenging than an average lesion • The bifurcation is a paradigm of Virchow’s triad (abnormal vessel wall, • rheology and coagulation) which create a thrombogenic evironment • 3. There is an inverse relationship between procedure complexity and • clinical outcome: • One stent > two (less is more) • KISSSSS principle (keep it simple swift and safe, surely with stents) • Teaching is important

4. Bifurcation and Stent Thrombosis What we know Cardiac Output The Starling curve LV Preload

5. Bifurcation and Stent Thrombosis What we know Good Clinical Outcome The Starling curve Poor Clinical Outcome Complex Simple 1 Wire + 1 Stent 2 Wires + 1 Stent 2 Wires + 1 Stent + kissing 3 Wires + Predil SB + 1 Stent + kissing Wires + Predil SB + 2 Stents + kissing Crush Culotte

6. Everything you always wanted to know aboutBifurcation and Stent Thrombosisbut were afraid to ask • What we know • What we thought we knew • What we don’t know • What we would like to know ?

7. Can we decrease the risk of stent thrombosis in bifurcation stenting? Bifurcation as a potent, independent risk factor for stent thrombosis n RR 95% CI FU Iakovou et al 2229 5.96 1.90 - 18.68 Subacute JAMA 2005 2229 8.11 2.50 - 26.26 Late Ong et al 1017 3.00 1.30 - 6.80 6 mo JACC 2005 Kuchulakanti et al 2974 4.40 1.96 - 10.00 12 mo Circulation 2006 French Registry 2551 3.70 1.80 - 7.60 EBC 2007 Hwang + Koo 10.21 4.75 – 21.92 Late TCT 2006

8. Can we decrease the risk of stent thrombosis in bifurcation stenting? Nordic Trial: ST at 14 months MV+SB (n=196) MV (n=199) Stent Thrombosis (%) 2.0 0.5 NS 5/395 = 1.2 % (Bern-R’dam registry: ±1.75% at 14 months) J. Lassen, personal communication

9. Can we decrease the risk of stent thrombosis in bifurcation stenting? One-year clinical outcome of PCI of bifurcation lesions in ARTS II • 607 patients with multivessel SES of whom • 324 had at least 1 bifurcation lesion • 283 no bifurcation lesion Non-Bifurcation Bifurcation P-value n=283 n=324 Death 1.1 0.9 1 Q-wave MI 0.7 0.9 1 Non-Q wave MI 2.5 4.9 0.14 MACCE 11 13 0.46 Stent Thrombosis 0.7 1.5 0.46 Tsuchida et al, EHJ 2007

10. Can we decrease the risk of stent thrombosis in bifurcation stenting? Bern-Rotterdam registry (n=8146 patients) Multivariate Cox proportional hazards model to identify the presence of a bifurcation lesion as an independant predictor of stent thrombosis Early ST 2.52 (1.26-5.02) * Late ST 0.22 (0.03-1.71) Overall ST 1.47 (0.79-2.72) Daemen et al, Lancet 2007

11. Bifurcation and Stent Thrombosis Bifurcation is a potent, independent risk factor for stent thrombosis What we thought we knew Late stent thrombosis is rare when up-to-date principles of ‘good stenting’ are applied

12. Bifurcation and Stent Thrombosis Goal : VASP < 50 % % of Pts Clopidogrel loading dose What we thought we knew Inhibition of Platelet Aggregation (%) 80 60 40 20 0 300 mg 600 mg Clopidogrel Hoffmann ESC 2005

13. Can we decrease the risk of stent thrombosis in bifurcation stenting? Variable responsiveness to Clopidogrel 135 patients receiving Plavix (75 mg/d) and Aspirin (100 mg/d) > 1 month ± 50% of patients have less than 50% reduction of platelet aggregation by LTA after 1 month of Pla/Asp J Angiollilo et al JACC 2007

14. Bifurcation and Stent Thrombosis What we thought we knew *Responder =  25% IPA at 4 and 24 h 100.0 80.0 Interpatient variability 60.0 Inhibition of platelet aggregation (%) 40.0 Interpatient variability 20.0 0.0 -20.0 Response to clopidogrel Response to prasugrel Brandt et al. ACC 2005

15. Everything you always wanted to know aboutBifurcation and Stent Thrombosisbut were afraid to ask • What we know • What we thought we knew • What we don’t know • What we would like to know

16. Bifurcation and Stent Thrombosis What we don’t know Is final kissing always mandatory?

17. Can we decrease the risk of stent thrombosis in bifurcation stenting? Thrombogenicity of the stent John Ormiston

18. Bifurcation and Stent Thrombosis FFR Diameter Stenosis (%) The angio cut-off value for (jailed) side branches is 75% DS - DS<75%: high NPV - Reason: - radiographic artefact (white halo) - small branches, small myocardial mass, low flow - Most likely idem with non-jailed SB - Oedema ? Like at day one after IMA implantations Bon-Kwon Koo et al JACC 2005

19. Changes in functional status of jailed SB - No intervention group (n=46) - Fractional Flow Reserve Koo BK, EHJ, in Revision

20. Everything you always wanted to know aboutBifurcation and Stent Thrombosisbut were afraid to ask • What we know • What we thought we knew • What we don’t know • What we would like to know

21. Bifurcation and Stent Thrombosis What we would like to know Is final kissing always mandatory? NORD-BIF III “Nordic kiss” main branch stenting only versus main branch stenting and final kissing balloon • N = 450, MV > 2.5 mm, SB > 2.25 mm • 1 and 6 month clinical- and 8 month angiographic follow up. • 14, 24 and 36 month safety follow up • FFR measurement in side branch (sub study) • Inclusion from April 1 2007.

22. Bifurcation and Stent Thrombosis What we would like to know • Is final kissing always mandatory? • What is the rate of distal LM LST • (Syntax LM patients) • Is clinical outcome influenced by • dedicated stent? • Is platelet aggregation testing clinically useful • or will it be overuled by newer • P2Y12 receptor blockers (Prasugrel, Cangrelor)