Reduction in Stent Thrombosis better tablets or better stents? Dr James Cotton MD FRCP Heart and Lung Centre Wolverhampton
MY CONFLICTS OF INTEREST ARE Speaker Fees/Honoraria/Travel Support Lilly/Daiichi Sankyo Schering-Plough The Medicines Company Medtronic Research Support J&J Cordis
% Stent Thrombosis 25 24 ASA and Oral Anticoag New Generation DES 20 ASA and Ticlopidine 15 10 5 0 Serruys 1991 Roubin 1992 7.6 6 1.4 0.5 Schatz 1991 Colombo 1995 Leon MB 1998 Moussa 1999 1.5 0.9 Cutlip 2001 ASA and Clopidogrel enaweser 2005 1.6 1 0.4 0.3 Moreno 2006 Khedi 2010 Stone 2010 Prasugrel Ticagrelor
Risk of Definite Stent Thrombosis Stable Angina UA/ NSTEMI STEMI Bare Metal Stents Drug Eluting Stents 0-0.5% 1.4-1.6% 2.9% 0.3-0.4% 1.2-1.9% 3.1% Cook, Windecker Circulation 2009
Angiographic DES Stent Thrombosis Bern - Rotterdam Cohort Study Cumulative probabiity of stent thrombosis (%) Wenaweser et al. ESC, Barcelona Sept 2006 N = 8,146 Patients (SES=3875;PES=4271) 3 2.9 % 2 1 Late 61 pts (40%) Incidence = 1.3/100 pts year 0 Early 91 pts (60%) N = 152 Patients Days after stent implantation 0 200 400 600 800 1000 1200 Cumulative Incidence 1.1% 1.2% 1.7% 2.3% 2.9%
Better Drugs?
Discontinuation of thienopyridine therapy:milan- Siegburg Cohort Study Airoldi F et al Circulation 2007 116:745-54
Stent Thrombosis and 2C19 polymorphisms Mega J et al JAMA 2010, 304(16) 1829-40
Inhibition of Platelet Aggregation (%) Clopidogrel (300 mg) vs. prasugrel (60 mg) Phase I healthy subjects 100.0 80.0 60.0 40.0 20.0 0.0-20.0 Response to clopidogrel *Responder = 25% IPA at 4 and 24 h clopidogrel responder clopidogrel non-responder Response to prasugrel Brandt JT et al. Am Heart J 2007;153:66.e9-e16
Inhibition of Platelet Aggregation (%) Clopidogrel (300 mg) vs. prasugrel (60 mg) Phase I healthy subjects 100.0 80.0 60.0 40.0 20.0 0.0-20.0 Response to clopidogrel *Responder = 25% IPA at 4 and 24 h clopidogrel responder clopidogrel non-responder Response to prasugrel Brandt JT et al. Am Heart J 2007;153:66.e9-e16
Stent Thrombosis* (%) 4 3 TRITON-TIMI 38: Stent thrombosis rates at end of study 52% RRR (1.2% ARR) P<0.0001 64% RRR (1.5% ARR) P<0.0001 48% RRR (1.1% ARR) P=0.0009 prasugrel clopidogrel 2 2.35 2.31 2.41 1 1.13 0.84 1.27 0 N=6,422 N=6,422 n=2,865 n=2,878 n=3,237 n=3,224 All Stents Drug-eluting Stents Bare-metal Stents *Stent thrombosis defined as Academic Research Consortium definite plus probable ARC = Academic Research Consortium ARR = Absolute Risk Reduction HR = Hazard Ratio NNT = Number Needed to Treat PCI = Percutaneous Coronary Intervention RRR = Relative Risk Reduction Wiviott SD et al. Lancet 2008;371:1353-1363
End Point (%) TRITON-TIMI 38: Life Threatening Bleeds at 15 months (All ACS) (n=6,716) (n=6,741) both + aspirin P=0.01 0.9% n=56 1.4% n=85 P=0.002 0.4% 0.1% n=21 n=5 P=NS 1.1% 0.9% n=64 n=51 P=NS 0.3% 0.3% n=17 n=19 Life Threatening Fatal Nonfatal Intracranial Subsets of Life Threatening Bleeds NS = Not Significant Wiviott SD et al. New Engl J Med 2007;357:2001-2015
Will duration of DAPT be key? DAPT - 2014 REAL LATE - 2011 OPTIDUAL - 2013
Better Stents?
New stent technologies
EC Strut Coverage (%) (14 Days) Comparative Endothelial Cell Coverage Rabbit Denudation Model (14 Days) p=0.05 Express vs. Liberte p=0.001 Express vs. Element Stent Strut Thickness (µm) Express Liberté Element Soucy. EuroPCR 2010
SPIRIT IV
The Abluminal Biodegradable Polymer DES PLA biodegradation and BA9 elution Abluminal biodegradable coating absorbed after 6-9 months * * I n vivo testing in porcine model demonstrates abluminal coating is absorbed after 6 to 9 months - Data on file at Biosensors Intl
Leaders Trial - Stent thrombosis
Other Bioabsorbable polymer studies COSTAR II ISAR-TEST 3 ISAR TEST 4 NOBORI CORE NOBORI-I RESELUTION No reduction ST for DES BP Vs DES PP Salinas P Abs AHA 2010 6032
Genous- E-healing Registry n=4939 Acute Thrombosis Subacute thrombosis 0.2% 0.7% Late Thrombosis 0.2% Silber S et al, Euro intervention In Press
Evolutions of Nevo Stent RES 1 ( no coating) 200 patients NO ST? Heparin coating may improve haemocompatability
Combo Bio-engineered Sirolimus Eluting Stent Granada, et al. CIRC Cardiovasc Interv, June 2010; 3
The Lancet Vol 373 March 14 2009
Absorb: histology and OCT
Further studies? Clinical trial aiming to demonstrate a reduction in ST from 0.4 to 0.2% 80% power 284,000 subjects!
? Training
THANKYOU
ARC Definitions of ST Definite Stent Thrombosis Angiographic or pathological conformation of partial or total thrombotic occlusion within the peri-stent region AND at least one of: Acute ischaemic symptoms Ischaemic ECG changes Elevated biomarkers Probable Stent Thrombosis Any unexplained death within 30 days of stent implantation Any MI related to ischemia in the territory of the implanted stent without angiographic conformation of ST Possible Stent Thrombosis Any unexplained death beyond 30 days