2 e forum interhospitalierdes guides de pratique. 27 octobre 2014

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1 2 e forum interhospitalierdes guides de pratique 27 octobre 2014

2 53 ans Me BOUCHARD DLP HbA1c à 5,9% FAP CHADS 2 de 0 Père DCD d un IM à 55 ans TVP il y a 10 ans AINS pour gonarthrose Dois-je continuer à prendre mon AAS?

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4 AAS et guides de pratique Mise à jour 2014 pour l'asmiq FA CHADS = 0 Diabète et prévention primaire MAP Péri-opératoire Prévention de la récidive de TEV André Roussin MD CHUM et ICM Professeur agrégé Université de Montréal

5 André Roussin MD, FRCPC Conflits d'intérêts potentiels Comités aviseurs ou aviseur expert: Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen et Pfizer Fonds de recherche: Astra-Zeneca, Bayer HealthCare et Sanofi Conférencier: Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Covidien, Leo, Merck, Pfizer et Sanofi

6 AAS: de Ramses II à nous Fuster V, Sweeny JM. Circulation. 2011;123:

7 Antiplaquettaires oraux 2014 (Canada et USA) Bloqueurs TxA2, ADP (P2Y12) et PAR-1 Antagonistes PAR-1 Vorapaxar (Zontivity ) ADP P2Y1 P2Y12 PAR-4 X X Antagonistes ADP récepteur P2Y12 TPα-R TPβ-R ADP Plaquette PAR-1 GP IIb-IIIa GP Ia-IIa GP VI TxA2 Ticlopidine(Ticlid ) Clopidogrel (Plavix ) Prasugrel (Effient ) Ticagrelor (Brilinta ) COX-1 X AAS GP IbαGP IX-GP V Fibrinogène Endothélium Collagène vwf Adapté, modifié, traduit et mis-à-jour à partir de: Angiolillo DJ et al. European Heart Journal (2010) 31, Plaquette

8 Impact des antiplaquettaires (AAS et autres) ATT Collaboration BMJ 2002; 324: 71-86

9 AAS et efficacité selon la situation clinique Situation RRR Incidence annuelle: IM + AVC + Mortalité vasc. Toutes confondues 25% 1 à 10% Prévention primaire 12 à 25% Framingham: < 2% SCA 30% 10% MCAS après un an 25% 5% FA 22% CHADS: ± 5% AIT et AVC aigus 11% 9% AIT et AVC long terme 22% 8% MAP 26% 5% Diabète seul 7 à 10% 3% selon nb. FR Récidive TEV long terme 32%? 5% pour TEV seule

10 AAS et saignements Inspiré de l étude CHARISMA Sans AAS Situation Incidence annuelle 0.5% pour saignements majeurs Saignements modérés.6% Saignements sévères.6% Saignements intra-cranien 0.13% Saignements fatals 0.09% Adapté de Bhatt D et al. NEJM 2006 et ATT Collaboration. Lancet 2009; 373:

11 FA: Warfarine comparée au placebo 1 RRR de 62% 1. Lip GYH et al. BMJ 2002; 325:

12 FA: AAS comparée au placebo 1 RRR de 22% 1. Lip GYH et al. BMJ 2002; 325:

13 FA: Warfarine comparée à AAS 1 RRR de 36% Warfarin better ASA better 1. Lip GYH et al. BMJ 2002; 325:

14 Fibrillation auriculaire: AVC / année Comparaisons entre thérapies Sans traitement 4.5% / an 1 AAS 3.7% / an 2 AAS + Clopidogrel 2.8% / an 2 Warfarine 1.7% / an 3 Dabigatran 110 BID 1.5% / an 3 Dabigatran 150 BID 1.1% / an 3 Sans FA: 0.6%/an 4 1 AF Investigators, Arch Int Med 1994:154: Active Investigators, N Engl J Med 2009;360: Connolly SJ et al, NEngl J Med 2009;361: Wolf et al, Stroke 1991;22:983

15 AAS selon SCC 2012, mise-à-jour MCAS ou MAP 2014 OAC aussi si > 65 ans Atrial Fibrillation Guidelines

16 FA: CCS 2014 Atrial Fibrillation Guidelines

17 AAS selon SCC 2010, 2012 et 2014 Atrial Fibrillation Guidelines

18 AHA-ACC 2014 AAS presque disparue sauf ± CHADS-VASc de 1

19 ESC 2012, utilisant aussi CHADS-VASc AAS quasi-évacuée, seulement si AC refusée

20 ESC 2012 AAS quasi-évacuée, seulement si AC refusée et, même là, AAS + Clopidogrel préférable Comme SCC 2014 Étude ACTIVE A

21 Diabète Dysfonction plaquettaire complexe HYPERGLYCAEMIA Increased P-selectin expression Osmotic effect Activation of PKC Decreased membrane fluidity by glycation of surface proteins DEFICIENT INSULIN ACTION Impaired response to NO and PGI 2 IRS-dependent factors: Increased intracellular Ca ++ degranulation ASSOCIATED METABOLIC CONDITIONS Obesity Dyslipidemia Inflammation OTHER CELLULAR ABNORMALITIES PLATELET ENDOTHELIAL DYSFUNCTION Increased platelet turnover Increased intracellular Ca ++ Upregulation of P2Y 12 signalling Oxydative stress H 2 O PKC IRS-1 Ca ++ Increased P-selectin and GP expression ROS/NOS Increased production of TF Decreased NO and PGI 2 production TF NO PGI 2 Ferreiro JL, Angiolllo DJ. Circulation 2011; 123: Endothelial cells

22 Aggrégation plaquettaire après 20 µmol ADP Les plaquettes diabétiques s aggrègent plus ITDM: insulin-treated diabetes mellitus, NDM: non-diabetes mellitus (patients), NITDM: non-insulin-treated diabetes mellitus. Maximum ADP (20 µmol/l)-induced Platelet aggregation (%) 80 P< NDM NITDM ITDM Angiolillo DJ et al. JACC 2006;48:

23 ATT 2009: prévention primaire vs secondaire RRR 12% RRR 19%

24 ATT 2009: meta-analyse et prévention primaire Selon l utilisation d autres médications préventives Risque MCAS < 5% Risque MCAS 5-10% Risque MCAS > 10% ATT Collaboration. Lancet 2009; 373:

25 Bénéfice clinique net "NNTreat vs NNHarm" Lancet 2009;373: NNT 70 NNT 47.2 NNH 2500 NNT 1000 NNH 1000 NNT 415 NNT Nombre de patients à traiter pendant 1 an pour prévenir 1 événement

26 AAS et Diabète: 2008 JPAD (sans MAP) et POPADAD (avec MAP asymptomatique) JPAD 2008 POPADAD 2008 AAS inefficace A Roussin

27 Meta-analyse 2009 en prévention primaire AAS et diabète AAS inefficace, surtout chez la femme De Berardis G et al. BMJ 2009; 339 A Roussin

28 Meta-analyse 2009 en prévention primaire AAS et diabète: événements CV majeurs De Berardis G et al. BMJ 2009; 339 RRR 10% ns A Roussin

29 ASA for 1⁰ Prevention in Diabetes Meta analysis of 6 studies (n = 10,117) No overall benefit for: Major CV events MI Stroke CV mortality All-cause mortality JPAD = Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes POPADAD = Prevention of Progression of Arterial Disease and Diabetes PPP = Primary Prevention Project ETDRS = Early Treatment Diabetic Retinopathy Study PHS = Physicians Health Study WHS = Women s Health Study guidelines.diabetes.ca BANTING ( ) diabetes.ca De Beradis Copyright G, et 2013 al. BMJ Canadian 2009; Diabetes 339:b4531. Association Major CV events JPAD 68/1262 POPADAD 105/638 WHS 58/514 PPP 20/519 ETDRS 350/1856 Total 601/4789 Myocardial infarction JPAD 28/1262 POPADAD 90/638 WHS 36/514 PPP 5/519 ETDRS 241/1856 PHS 11/275 Total 395/5064 Stroke JPAD POPADAD WHS PPP ETDRS Total No. of events/no. in group ASA Control/placebo RR (95% CI) RR (95% CI) 12/ /638 15/514 9/519 92/ /4789 Death from CV causes JPAD 1/1262 POPADAD 43/638 PPP 10/519 ETDRS 244/1856 Total 298/4275 All-cause mortality JPAD POPADAD PPP ETDRS Total 34/ /638 25/ / / / /638 62/513 22/ / / / /638 24/513 10/ / / / / /638 31/513 10/512 78/ / / /638 8/ / / / /638 20/ / / Favors ASA 0.80 ( ) 0.97 ( ) 0.90 ( ) 0.90 ( ) 0.90 ( ) 0.90 ( ) 0.87 ( ) 1.10 ( ) 1.48 ( ) 0.49 ( ) 0.82 ( ) 0.40 ( ) 0.86 ( ) 0.89 ( ) 0.74 ( ) 0.46 ( ) 0.89 ( ) 1.17 ( ) 0.83 ( ) 0.10 ( ) 1.23 ( ) 1.23 ( ) 0.87 ( ) 0.94 ( ) 0.90 ( ) 0.93 ( ) 1.23 ( ) 0.91 ( ) 0.93 ( ) 2 8 Favors control/placebo

30 Bell A, Roussin A et al. Can J Cardiol 2011;27:S1-59

31 Diabète: CCS 2010 Prévention primaire There is currently no evidence to recommend routine use of ASA at any dose for the primary prevention of vascular ischemic events in patients with diabetes Class III, Level A Donc AAS inutile Kraw ME, Rabasa-Lhoret R. CCC 2010 A Roussin

32 Diabète: CCS 2010 Prévention primaire Even if there was a 10% reduction in the risk of primary events, the NNT in order to prevent 2 major cardiovascular events would be 1000 patients for 1 year. Taking into account rare but well-documented side effects such as major bleeding, such benefit might be questionable even with a low-cost medication such as ASA Donc NNT 2000 pour 1 an Kraw ME, Rabasa-Lhoret R. CCC2010 A Roussin

33 Diabète: CCS 2010 Prévention primaire En présence d'autres facteurs de risque For patients with diabetes aged more than 40 years and at low risk for major bleeding, low-dose ASA ( mg daily) may be considered for primary prevention in patients with other cardiovascular risk factors for which its benefits are established Class IIb, Level B À considérer Kraw ME, Rabasa-Lhoret R. CCC2010 A Roussin

34 Diabète et prévention primaire 34 Antiplatelet therapy in patients with diabetes Primary prevention Bell A, Roussin A et al. Can J Cardiol 2011;27:S1-59

35 ADA 2011: AAS en prévention primaire Risque cardiovasculaire < 5% sur 10 ans Aspirin should not be recommended for CVD prevention for adults with diabetes at low CVD risk (10-year CVD risk < 5%, such as in men < 50 years of age and women < 60 years of age with no major additional CVD risk factors), since the potential adverse effects from bleeding likely offset the potential benefits (C) Donc AAS inutile si Risque CV < 5% A Roussin

36 ADA 2011: AAS en prévention primaire Risque cardiovasculaire 5-10% sur 10 ans In patients in these age-groups with multiple other risk factors (e.g. 10-year risk 5 10%), clinical judgment is required. (E) Donc AAS possible si risque CV 5-10% A Roussin

37 ADA 2011: AAS en prévention primaire Risque cardiovasculaire >10% sur 10 ans Consider aspirin therapy ( mg/ day) as a primary prevention strategy in those with type 1 or type 2 diabetes at increased cardiovascular risk (10- year risk >10%). This includes most men < 50 years of age or women < 60 years of age who have at least one additional major risk factor (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria). (C) Donc AAS acceptable si risque CV >10% A Roussin

38 CDA 2013 Use a Multifaceted Vascular Protection Strategy Healthy Lifestyle/weight Smoking Cessation Physical Activity BP <130/80 A1C 7% Rx: Statins ACEi/ARB Vous remarquez quelque chose? guidelines.diabetes.ca BANTING ( ) diabetes.ca Copyright 2013 Canadian Diabetes Association

39 CDA 2013 Vascular protective medications Statins ACE-inhibitors or Angiotensin receptor blockers (ARB) ASA selective use Voilà!

40 2013 CDA 2013 ASA Not Routinely Recommended for 1⁰ Prevention for CVD Among Patients with DM Insufficient evidence to support use of ASA for primary prevention Risk of bleeding CVD protection guidelines.diabetes.ca BANTING ( ) diabetes.ca Copyright 2013 Canadian Diabetes Association

41 CDA 2013 Vascular Protection Checklist 2013 A A1C optimal glycemic control (usually 7%) B BP optimal blood pressure control (<130/80) C Cholesterol LDL 2.0 mmol/l if decided to treat D Drugs to protect the heart A ACEi or ARB S Statin A ASA if indicated E Exercise regular physical activity, healthy diet, achieve and maintain healthy body weight S Smoking cessation guidelines.diabetes.ca BANTING ( ) diabetes.ca Copyright 2013 Canadian Diabetes Association

42 guidelines.diabetes.ca BANTING ( ) diabetes.ca

43 Diabète: Continuum de risque et AAS Patient asymptomatique sans diabète Pas AAS Diabétique asymptomatique avec peu de facteurs de risque (sans HTA?). Pas AAS Diabétique asymptomatique avec plusieurs facteurs de risque (dont HTA?). AAS? Diabète symptomatique AAS et/ou clopidogrel (prasugrel /ticagrelor / dipyridamole-asa ) A Roussin

44 Études en cours ASCEND UK AAS 100 mg et Omega-3 Double insu pour 5 ans 10,000+ patients > 40 ans ACCEPT D Itaiey AAS 100 mg + simvastatine mg Simple insu pour 5 ans 5170 patients > 50 ans A Roussin

45 Impact des antiplaquettaires APT coll. Study BMJ 2002; 324: 71-86

46 Bell A, Roussin A et al. Can J Cardiol 2011;27:S1-59 Maladie artérielle périphérique CCS 2010

47 Antiplaquettaires et interventions: CCS 2010 Test diagnostiques 1. Patients who are receiving ASA and undergoing a diagnostic test associated with a low risk for bleedingmay continue ASA without interruption, whereas patients undergoing a noncardiac procedure associated with a high risk for bleeding should discontinue ASA 7-10 days before the procedure (Class IIa, Level C) Patients who are receiving ASA and clopidogrelshould discontinue clopidogrel 7-10 daysbefore the procedure if it can be done so safely (Class IIb, Level C) ASA should also be discontinued before diagnostic tests associated with a high risk for bleeding (Class IIa, Level C) Bell A, Roussin A et al. Can J Cardiol 2011 ; 27:

48 Antiplaquettaires et interventions: CCS 2010 Chirurgie élective et stents 2. Whenever possible, elective surgery in patients receiving ASA and clopidogrel secondary to coronary stent implantation should be deferred for at least 6 weeks after BMS placement and at least 12 months after DES placement (Class I, Level B) 6 months ACCP 2012 Bell A, Roussin A et al. Can J Cardiol 2011 ; 27:

49 Antiplaquettaires et interventions: CCS 2010 Chirurgie urgente et stents 3. For patients who are receiving ASA and clopidogrel for a BMS and require urgent surgery within 6 weeks of placement, ASA and clopidogrel should be continued in the perioperative period (Class I, Level B) For patients who are receiving ASA and clopidogrel for a DES and require urgent surgery within 12 months of placement, ASA and clopidogrel should be continued in the perioperative period (Class I, Level B) 6 months ACCP 2012 Bell A, Roussin A et al. Can J Cardiol 2011 ; 27:

50 Antiplaquettaires et interventions: CCS 2010 Ponctions articulaires 4. Patients who are receiving ASA and are to have arthrocentesis may continue ASA through the time of the procedure (Class IIb, Level C) Patients who are receiving ASA and clopidogrel should discontinue clopidogrel 7-10 days before the procedure if it can be done safely (Class IIb, Level C) Bell A, Roussin A et al. Can J Cardiol 2011 ; 27:

51 Antiplaquettaires et interventions: CCS 2010 Chirurgie mineure 5. Patients who are receiving ASA and are undergoing a minor dental, eye or skin procedure/surgery may continue ASA around the time of the procedure (Class IIa, Level A) Patients who are receiving ASA and clopidogrel should discontinue clopidogrel 7-10 daysbefore the procedure if it can be done safely (Class IIa, Level C) Bell A, Roussin A et al. Can J Cardiol 2011 ; 27:

52 Antiplaquettaires et interventions: CCS 2010 Chirurgie majeure 6. Patients who are receiving ASA and require elective noncardiac surgery should discontinue ASA 7-10 days prior to surgery if the risk for cardiovascular events is low but continue therapy if cardiovascular risk is high (Class IIa, Level B) Patients who are receiving ASA and clopidogrel, who are likely to be at high cardiovascular risk, should continue ASA up to surgery (Class IIa, Level C) but discontinue clopidogrel 7-10 days before surgery if it can be done so safely (Class IIb, Level C). Bell A, Roussin A et al. Can J Cardiol 2011 ; 27:

53 Antiplaquettaires et interventions: CCS 2010 Pontage aorto-coronarien 7. Patients who are receiving ASA and require CABG should continue ASA up to the time of surgery (Class I, Level B) Patients who are receiving ASA and clopidogrel should continue ASA until the time of surgery but discontinue clopidogrel at least 5 days before surgery (Class I, Level B) Bell A, Roussin A et al. Can J Cardiol 2011 ; 27:

54 AAS et récidive de TEV Efficacité de 32% (aucun consensus ou guide) Deux études comparant AAS au placebo chez pts. avec 1ère TVP idiop. après 6-18 mois d'ac Analyse groupée des patients sous AAS: Réduction de 32% de récidive de TEV (p=0.007) Réduction de 34 % évén. vasc. majeurs (p=0.002) Pas d'augmentation des saign. majeurs et clin. signigf. Meilleur chez hommes et patients > 65 ans Becattini C, et al. N Engl J Med. 2012; 366(21): WARFASA Brighton TA, et al. N Engl J Med. 2012; 367(21): ASPIRE Simes J, et al. Circulation 2014; on-line INSPIRE

55 AAS et récidive de TEV Efficacité comparée des diverses options

56 AAS et récidive de TEV Efficacité comparée et suggestion publiée Wakefield TW, et al. Circulation 2014; on-line

57 AAS et EP Recommandations officielles 2014

58 AAS et récidive de TEV Efficacité de 32% (aucun consensus ou guide) BREF: AAS non indiquée en traitement initial AAS n'est pas aussi efficace qu'un AC Becattini C, et al. N Engl J Med. 2012; 366(21): WARFASA Brighton TA, et al. N Engl J Med. 2012; 367(21): ASPIRE Simes J, et al. Circulation 2014; on-line INSPIRE

59 53 ans Me BOUCHARD DLP HbA1c à 5,9% FAP CHADS 2 à 0 Père DCD d un IM à 55 ans TVP il y a 10 ans AINS pour gonarthrose Dois-je continuer à prendre mon AAS? Pas si c'est pour des raisons vasculaires

60 Références Canadian Cardiovascular Society Guideline on the Use of Antiplatelet Therapy in the Outpatient Setting