Colloque du département de chirurgie

4 février 2008

%

Circulation. 1989;80:421– 428Ann Intern Med. 2003;138:777–786

Bare Metal Stents

Circulation. 1989;80:421– 428 N Engl J Med 1998;339:1665-71

Death, revascularization of the target lesion, angiographically evident thrombosis, or myocardial infarction

N Engl J Med 1998;339:1665-71

K. Toutouzas. Eur Heart J. 2004

Keller P-F. Expert Opin Emerg Drugs. 2005 Feb;10(1):67-86

Bare Metal Stent (BMS)

Drug Eluting Stent (DES)

DES to fight re

stenosis

26%

0%0%

5%

10%

15%

20%

25%

30%

Ang

iogr

aphi

c R

este

nosi

s (%

)

Bare Stent Sirolimus Coated

P<0.001

Restenosis

MA

CE

Fre

e S

urvi

val (

%)

P<0.001MACE Free

RAVEL: ResultsRAVEL: Results

Bare Stent Sirolimus Coated

n=237, 6 months follow-up

Morice MC. N Engl J Med 2002;346:1773

DES vs BMS

Forest plot comparing rates of angiographic restenosis for DES and for BMS

Forest plot comparing rates of MACE for DES and for BMS

Forest plot comparing all-cause mortality rates for DES and for BMS

Forest plot comparing MI rates for DES and for BMS

Babapulle MN. Lancet 2004; 364: 5836–12 months of angio & clinical FU, n=5103

Concern about Drug Eluting-Stents: In-Stent Thrombosis

?

¡ Definite: ACS + angio or autopsy of stentthrombosis

¡ Probable: Probable stent thrombosisincluded unexplained deaths within 30 daysafter the procedure or acute myocardial infarction involving the target-vessel territory without angiographic confirmation.

¡ Possible stent thrombosisincluded all unexplained deaths occurring at least 30 days after the procedure. Intervening target lesion revascularization was defined as any repeated percutaneous revascularization of the stented segment, including the 5-mm proximal and distal margins, that preceded stent thrombosis.

Stone G. ACC 2006

Stone G. ACC 2006

Stone G. ACC 2006

Lancet 2007; 369: 667–78

Eur Heart J 2005; 26: 1180–1187 BMS

DES

N=6058

N=8146

Stent thrombosisN=126 (0.87%)

Cardiac deathN=20551 stent thrombosis (25%)

Myocardial infarctionN=16855 stent thrombosis (33%)

3528 %

3931 %

1613 %

3628 %

Urban P. Circulation. 2006;113:1434

n = 15’157 patients

41% mortality

Late thrombosis 0.19%. 12-months actuarial incidence of stent thrombosis 0.87%

Iakovou I. JAMA. 2005;293:2126

00.20.40.60.8

11.21.41.61.8

Thrombosis

TotalSESPES

%

1.3 %

0.8 %

1.7 %

Clopidogrel or Ticlopidine : 3 months for SES, 6 months for PES

Mortality : 45%

12 months FU

p=NS

N=2229 consecutive pts

Independent predictors of stent thrombosis (ST)

Am J Cardiol 2006;98:352–356

Lancet 2007; 369: 667–78

N=8146ST=152

Daemen J. Lancet. 2007 May 26;369(9575):1785-1786

Daemen J. Lancet. 2007 May 26;369(9575):1785-1786

Décision de la FDA en décembre 2006 de reconnaître l’indication au Clopidogrel pour une durée de 12 mois après l’implantation d’un stent

médicamenté

• The incidence of stent thrombosis isincreased between 31 and 365 daysfor DES compared with BMS

• Clopidogrel withdrawal is correlatedwith the increased risk of stent thrombosis

Months of followMonths of follow--upup00 11 22 33 44 55 66 77 88 99 1010 1111 1212

20% RRR20% RRRpp=0.00009=0.00009n=12,562n=12,562

AspirinAspirinClopidogrel + AspirinClopidogrel + Aspirin

00

1010

1414

1212

44

88

66

22

N Eng J Med 2001;345:494N Eng J Med 2001;345:494

Benefits were seen within hours and continued to increase

over the 12 months

Cumulative Events [%](Cardiovascular Death, Myocardial Infarction, or Stroke)

CURE: Early & Long-Term Benefits of Clopidogrel following an ACS w or w/o

Stent

Angine stable Angine instable NSTEMI STEMI

PCI, thrombolyse +

traitement médical

PCI+

traitement médicalTraitement médical

PCI

Prise en charge:

Antiplaquettaires lors de PCI:

Dilatation, BMS: 9-12 moisDES: min. 12 mois

BMS: 4 sem.DES: min. 12 mois

Antiplaquettaires lors traitement médical:

Par analogie avec NSTEMI:Clopidogrel+AAS: 9-12 mois

Clopidogrel + AAS: 9-12 mois(ESC Guidelines on NST-ACS 2002)

AASClopidogrel si intolérance

Dose de charge

Utiliser dose de charge de 300 mg.Si > 6h avant intervention 300mg, si < 6h utiliser 600 mg.

Lors de PCI primaire et thrombolyse: dose de charge

de 600 mg.

traitement médical+/-PCI

¡ 383 patients with known CAD were hospitalized for ACS:

§ 51 (13.3%) of these ACSs occurred within 1 month after aspirin withdrawal.

§ 10 pts (20%) had a thrombosis of Bare Metal Stent implanted on average 15.5±6.5 months previously.

Ferrari E. J Am Coll Cardiol 2005;45:456

40 patients underwent surgery 1 to 39 days after coronary stent placement (average 13 days).

¡ 8 out of 40 patients (20%) died: ▪ 6 MI▪ 2 major bleeding complications

¡ Stent thrombosis was presumed to be the cause of all of the MI.

¡ All deaths and MI (7 MI) as well as 8 of 11 bleeding episodes occurred in patients who underwent surgery in less than two weeks after coronary stent placement.

¡ Mortality rate among 25 patients operated within this two-week timeframe was 32%.

J Am Coll Cardiol 2000;35:1288

207 patients underwent surgery within 2 months after coronary stent placement:

¡ 8 out of 207 patients (4.0%) died or suffered amyocardial infarction or stent thrombosis.

¡ All 8 patients were among the 168 patientsundergoing surgery within the six weeks

periodfollowing stent placement

¡ No events occurred in the 39 patients undergoingsurgery seven to nine weeks after stent

placement.

J Am Coll Cardiol 2003;42:234

Catheter Cardiovasc Interv 2004;63:141–145

n=47

All Pts under Heparin

Catheter Cardiovasc Interv 2004;63:141–145

n=47

All Pts under Heparin

6/7 Death following ThienopyridinDiscontinuation

JACC 2007;49:122-124

n=192

Late: after Thienopyridin discontinuation or Early: before Thienopyridin discontinuation

Patients With Early Surgery (n 30) After PCI Who Either Continued or Discontinued Antiplatelet Therapy

JACC 2007;49:122-124

• Early Non-Cardiac Surgery after Stenting increase the risk of MACE

• Early Antiplatelet Therapydiscontinuation markedly increasethe risk of MACE

JACC 2007;49:122-124

Incidence of All-Cause Death or MI According to the Allocated Strategy in Patients With 3 or More Cardiac Risk Factors With Extensive Stress-Induced Ischemia

Med therapy + prophylactic revascularization

Med therapy

J Am Coll Cardiol 2007;49: 1763–9

n=102

Preoperative risk stratification

Team

Surgeon/Anesthesiologist

Cardiologist

Generalist-Internist

Patient

¡ Whilst aspirin increased the rate of bleedingcomplications by factor 1.5 (median, interquartile range: 1.0–2.5), it did not lead to a higher level of the severity of bleeding complications (exception: intracranial surgery, and possibly transurethral prostatectomy)

Operation with Aspirin

European Journal of Cardio-thoracic Surgery 25 (2004) 419–423n=1628 consecutive patients, 48 under Clopidogrel Therapy

Operation with dual antiplatelet Tx

194 patients who underwent angioplasty a median of 11 days (3-49) prior to major

noncardiac surgery.

¡ 13.4 % Cardiac morbidity (angina, heartfailure, or arrhythmia).

¡ 0.5 % death or MI.Gottlieb A. J Cardiothorac Vasc Anesth 1998;12:501

Balloon angioplasty

¡ Beaucoup moins de risque à maintenir les antiplaquettaires que de les arrêter avant une chirurgie majeure non cardiaque:§ Augmentation du risque hémorragique et

transfusionnel de 30-50%, sans ↑ mortalité ou morbidité chirurgicale sauf en espace clos (neurochir, chambre postérieure)

¡ Beaucoup moins de risque à maintenir les antiplaquettaires que de les arrêter avant une chirurgie majeure non cardiaque:§ Risque élevé de thrombose de stent en cas

d’arrêt des antiplaquettaires ~30% avec 20-45% mortalité§ En cas de transfusion plaquettaire, effet des

antiplaquettaires négligeable:▪ > 12 heures pour le Clopidogrel▪ > 6 heures pour Tirofiban et Integrilin▪ > 48 heures pour Reopro

Ajuster le traitement anti-plaquettaire

¡ Opération urgente ou semi-urgente:

§ Si l’opération peut attendre > 6 semaines → BMS ou CABG§ Si opération vitale < 4 semaine: Angioplastie

au ballon seul§ Si urgence vitale < 72 heures: pas

d’investigation§ DES seulement si indiqué et si chirurgie

élective > 12 mois

Previous PCI

Balloon PCI BMS DES

<14Days >14Days >30-45Days <30-45Days

<365Days>365Days

Delay for elective or non-urgent

Surgery

Proceed to surgery with Asa

Delay for elective or non-urgent

Surgery

Proceed to surgery with Asa

Time since PCI

JACC Vol. 50, No. 17, 2007

Previous PCI

Balloon PCI BMS DES

<14Days >14Days >30-45Days <30-45Days

<365Days>365Days

Delay for elective or non-urgent

Surgery

Proceed to surgery with Asa

Delay for elective or non-urgent

Surgery

Proceed to surgery with Asa

Time since PCI

Call Cardiologist

First

JACC Vol. 50, No. 17, 2007

Patients sous ASA75-150mg/j

Préventionprimaire

JACC Vol. 50, No. 17, 2007

Patients sous ASA 75-150mg/j+ Clopidogrel 75mg/j

Stop 7 j préop

Préventionsecondaire

Neurochir intracrânienne

Toute chirurgie

Opération sous traitement continu

Haut risque coronarien• < 4-6 semaines post BMS,

infarctus ou AVC• < 12 mois post DES• Lésion stentée complexe

Chirurgie vitaleseulement

Risque hémorragiqueen espace clos

Faible Risque coronarien> 6 semaines post BMS>3 mois post infarctus ou AVC non compliqués

Toute chirurgie

Stop ClopidogrelContinuer Asa

Patients sous ASA75-150mg/j

Préventionprimaire

JACC Vol. 50, No. 17, 2007

Patients sous ASA 75-150mg/j+ Clopidogrel 75mg/j

Stop 7 j préop

Préventionsecondaire

Neurochir intracrânienne

Toute chirurgie

Opération sous traitement continu

Haut risque coronarien• < 4-6 semaines post BMS,

infarctus ou AVC• < 12 mois post DES• Lésion stentée complexe

Chirurgie vitaleseulement

Risque hémorragiqueen espace clos

Faible Risque coronarien> 6 semaines post BMS>3 mois post infarctus ou AVC non compliqués

Toute chirurgie

Stop ClopidogrelContinuer Asa

Contacter le cardiologue interventionnel

¡ 5 Days before surgery Cease Clopidogrel¡ 3 Days before Surgery admit to hospital

Begin Tirofiban Bolus, Infusion, and UFH¡ 6 Hours before surgery Cease Tirofiban

and UFH¡ 1st post op Day start 600mg loading dose

Clopidogrel followed by maintenance dose the next Day¡ Aspirine continued throughout

Br J Anaesth 2007; 98:19–22

Merci