World Congress of Cardiology PARIS: August 27-31, ESC Andreas Gruentzig lecture on Interventional Cardiology

Transcription

1 World Congress of Cardiology PARIS: August 27-31, 2011 ESC Andreas Gruentzig lecture on Interventional Cardiology Stent optimization and dual antiplatelet therapy: what has been done and what needs to be done to make coronary stenting safe Antonio Colombo Centro Cuore Columbus and S. Raffaele Scientific Institute, Milan, Italy

2 Presenter Disclosure Information Antonio Colombo, MD Co-founder & minor shareholder: Cappella Inc.

3 Stent thrombosis: concepts outlined here are the leitmotif of this presentation Mammary artery conduits seem independent from these 3 concepts The stool stands only if each leg is solid: one leg with extra strength does not compensate for the broken one Lumen Leg: optimal MLD, no persistent dissection or lesion Run off leg: TIMI 3 flow, good distal blush, healthy distal microcirculations, functional distal myocardium Blood leg: optimal antiplatelet therapy, acceptable clopidogrel and aspirin response, compliance of the patient to dual antiplatelet therapy.

4 «Proof of Concept» June 1986 NEJM 1987 Ulrich Sigwart and Jacques Puel

5 Self-expanding mesh stent

6 Stent explanted from a Dog after 8 month

7 EM photos of the endothelial surface of a dog coronary about a year out with silver staining showing normal appearing borders and tight junctions suggesting a physiologically "normal surface. Thus theoretically resistant to thrombosis.

8 NEJM 1991 Therapy: aspirin+dypiridamole +subcute heparin for 6 weeks 117 patients: 21 stent occlusions within 14 days, 8 deaths in the first year

9 RANDOMIZED STUDY IN DOGS, in 1999 No Anticoagulation Heparin, Aspirin, Dipyridamole Heparin, Aspirin, Dipyridamole, Dextan

10 Subacute Thrombosis after Stenting: historical data without dual antiplatelet therapy and no high pressure implantation % Wallstent 3.5% 3.4% 5.7% n=308 n=262 n=205 n=164 NEJM 1991 Benestent STRESS Munich CCD 1994 NEJM 1994 NEJM 1994 JACC 1994 Systemic Anticoagulation

11 Hemorrhagic Complication Rate Palmaz-Schatz Stent Percentage (%) Author (year) Pts Groin Gastro-int.Total Sigwart (1988) Schatz (1991) Haude (1991) de Scheerder(1992) Roubin (1992) Herrman (1992) Benestent I(1994) Total

12 My first case of stent thrombosis January 1990, unstable angina with LAD restenosis following PTCA Baseline

13 My first case of stent thrombosis Lesion predilatation and stent placement POBA 2.5mm, 7atm 3.0mm balloon, 9atm Post stent implantation

14 My first case of stent thrombosis Two days later while patient on heparin infusion just started oral anticoagulants, dypiridamole and aspirin Sudden chest pain and ST elevation Stent thrombosis and Ventricular Fibrillation

15 My first case of stent thrombosis Final result

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17 My first case of stent thrombosis January 25, 1990 T Thank you very for sending the film. I am vitally interested in every complication so I can continue to learn from every case

18 My first case of stent thrombosis If I have to point out few things that may have contributed: the omission of Persantine prior to the procedure, inflow obstruction and underdilatation of the stent were factors. Don t be discouraged by this one set back. I believe these thrombosis are rare occurances. Richard A. Schatz, M.D.

19 NEED Something different from heparin or coumadin Better stent expansion

20 NEJM 1989 Ticlopidine gave a 21% risk reduction of stroke at 3 years compared to aspirin

21 Why did I pursue Ticlopidine? Dr. Paul Barraghan: If you start A Ticlopidine cardiac surgeon: few days There before is PTCA no question and that Ticlopidine continue you causes will have a malignant less dissections bleeding. I will not operate on any patient who is receiveing which will occlude. Ticlopidine.

22 1994

23 238 pts IV heparin during stenting Thrombosis at 30 days 4.2% Ticlopidine 500 mg before and after stenting 3-6 mo Subcutaneous heparin for 1 wk 3.5% 7.9% No mention about deployment pressure Elective Threatened Closure Barragan et al CCD 1994

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25 After stent implantation Post-dilation Balloon 4.0 mm - 26 Atm Final Result after IVUS optimization 9-mo Follow-Up

26 Jailed wires for side-branch protection side branches are selectively wired Baseline Side-Branch protection 12391/05

27 Jailed wires for side-branch protection Final Result If SBs remain open without protection it means that the stent is not fully expanded!! 12391/05

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29 Coronary stenting without anticoagulation 359 patients on Aspirin + Ticlopidine+ IVUS evaluation Aspirin + Ticlopidine in most pts Average balloon pressure 14.9 atm Balloon artery ratio 1.17 Thrombosis 0.9% Colombo et al Circulation 1995

30 EVENTS AT 30 DAYS STARS Trial, in 1998 The antithrombotic effect of adding ticlopidine to aspirin Aspirin alone (N=557) Aspirin+Warfarin (N=550) Aspirin+Ticlopidine (N=546) 3.6% I am puzzled that 96.4% of patients who took only aspirin did not experience stent thrombosis 2.5% P< *Death, TLR, thrombus, MI Primary endpoint* 0.5% Leon MD et al N Eng J Med 1998; 339:

31 Individual 58 patients (each line bar is a patient) Occurrence of Stent Thrombosis following implanttion of TAXUS or CYPHER in 3029 pts F.Airoldi and A.Colombo Circulation cases of thrombosis 1.9%, in 3029 pts Dual antiplatelet therapy Stop one antiplatelet agent Thrombotic event Almost half thrombosis occurred in the first months 2/3 of them in the first 6 months and most thrombotic events in patient on dual antiplatelet therapy Time (days)

32 Over 85% Antiplatelet of early stent treatment thrombosis at the occurred time of in patients taking DES thrombosis dual antiplatelet in 152 therapy patients Dual antiplatelet therapy 100% 80% 4.4 Single antiplatelet therapy No antiplatelet therapy 60% 40% % 0% 86.7 Early stent thrombosis 23.0 Late stent thrombosis Windecker and Meier Circulation 2007

33 Of 21,009 patients treated with either a bare-metal or drug-eluting stent, 437 patients (2.1%) presented with a definite ST. A total of 140 STs were acute, 180 were subacute, 58 were late, and 59 were very late. van Werkum et al. JACC Vol. 53, No. 16, 2009

34 The Dutch Stent Thrombosis Registry Independent Risk Factors for ST The usual offenders: suboptimal stents results and antiplatelet therapy van Werkum et al. JACC Vol. 53, No. 16, 2009

35 Angiographic, IVUS and procedural variables Insufficient emphasis has been done regarding the interaction of different procedural variables such as: a long stent+ a small MLD or a subotptimal TIMI flow or a small distal bed. Even if never clearly investigated some of these interactions are very important and may explain many early stent thrombosis

36 RECLOSE: Stent Thrombosis according to the response to clopidogrel This 5 field is far from being settled because 4.8 data are still conflicting regarding the best Responders (n = 699) % 3 2 test to utilize to evaluate platelet Nonresponders (n = 105) inhibition and regarding the value which needs to be considered abnormal Subacute Late Buonamici.Antoniucci; JACC 2007

37 CYP2C19*2 genotypes and stent thrombosis in 2485 patients 45 patients not activating clopidogrel did not experience stent thrombosis Odd ratio for ST= pts 633 pts 47 pts Sibbing et al European Heart Journal (2009) 30, 916

38 Prasugrel versus Clopidogrel 13,608 patients Prasugrel Clopidogrel BMS 48% 47% DES 47% 47% Stent Thrombosis (ARC d+prob) 1.1% 2.4% BMS HR 0.52 (95% CI ) P< DES HR 0.43 (95% CI ) P< NEJM 2007

39 Facts We now know that 20-15% of patients do not optimally respond to clopidogrel and 3-5% do not respond at all There are tests (genetic or point of care) which may help to identify some of these patients There are alternative drugs: prasugrel/ticagrelor which are effective for clopidogrel poor responders

40 Actions Prasugrel or ticagrelor instead of clopidogrel: One Size Fits All Identify non-responders and treat them with prasugrel/ticagrelor: Selective approach No matter what: some action needs to be taken!

41 The Lancet 2004 The authors report four cases of stent thrombosis occurring between 343 and 442 days from Taxus or Cypher implantation causing myocardial infarction. All cases arose soon after ALL antiplatelet therapy was stopped.

42 Progressive Peri-Stent Staining and Very Late Stent Thrombosis: Drug or Polymer toxicity to the vessel wall Imai M,..Kimura T, Mitsudo K; Circulation 2011;123: Kon H, et al. Circ Cardiovasc Interv 2011;4:e1-3

43 Individual reports and meta-analysis of randomized trials showed no significant increase in risk (thrombosis) associated with drug-eluting stents as compared to bare-metal stents, at 1 year (Stone et al. Circul. 2004; Holmes et al. Circul. 2004; Moreno et al. JACC 2005). When we use DES we suggest to continue dual antiplatelet therapy for 1 year, we are reluctant to use DES in patients who cannot take dual antiplatelet therapy, we use BMS in these situations! Thrombosis rates after drug-eluting stents implantation may be similar to the ones after bare-metal stents implantation but the duration of antiplatelet therapy is different

44 Def/Prob Stent Thrombosis (%) Two-year cumulative rates of definite/probable stent thrombosis rates according to the type of stent implanted 5 4 HORIZONS 4.4% 3 BMS 2 1 Taxus Taxus BMS Only Time in Months Dangas et al Circulation 2011;123:

45 Stent thrombosis with second generation drug-eluting stents Stents conceived after Taxus and Cypher. Drug-eluting stents with thin struts, thin polymers, bioabsorbable polymers, no polymers

46 RESOLUTE All Comers Trial Cumulative frequency of ARC definite and probable stent thrombosis up 2 years Composite of ARC definite and probable stent thrombosis and any death up to 2 years ARC=Academic Research Consortium Silber et al Lancet 2011; 377:

47 Everolimus Eluting Stents vs. Sirolimus Eluting stents RCTs with > 1000 Patients Definite Stent Thrombosis Stone GW EuroPCR 2011 When you evaluate definite and probable stent thrombosis (the current gold standard) differences disappear

48 Circulation 2000;102:

49 A We are always Bioabsoption enthused and by Late the enlargement fact that of lumen the polymer, the drug and the stent go away. As interesting it can be this feature is not a sufficient demonstration of safety. Even B radiations go away but they leave remarkable hallmarks! Pre-stenting Post-stenting 6-month 24-month Lumen area, mm 2 (n=16) Maintains the possibility for vessel remodelling

50 A pitfall related to disease progression

51 Thrombosis or disease progression? 26 June 2003 Baseline 11561/03

52 Thrombosis or disease progression? 26 June 2003 Final result following LAD and Diagonal Cypher Stents 11561/03

53 Thrombosis or disease progression? 8 mo Follow-Up 8 months Later 17 February October 2004 Patient asymptomatic, Stress Test Negative 11561/03

54 Conclusions Stent thrombosis has almost been conquered Early (acute and subacute) thrombosis remains an important problem compared to late thrombosis: continuous efforts to improve on dual antiplatelet therapy and stent implantation will help Hopefully, late and very late thrombosis will be reduced by new generations stents and possibly bioabsorbable stents. Disease progression remains an offender