Commentaires sur les principaux essais cliniques présentés à lESC 2009 Damien Coisne.

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1 Commentaires sur les principaux essais cliniques présentés à lESC 2009 Damien Coisne

2 Différentes voies dinhibition= différentes voies de recherche

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4 PLATO Lars Vallentin Perspective Clopidogrel Prasugrel Ticagrelor Albert Schoming Editorial NEJM 2009, 361,11, 1108 Rapidité daction Variabilité interindividuelle Reversibilité Risque hémorragique Efficacité clinique

5 Perspective Cure/Triton/Plato

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7 Le progression de CURE vers TRITON sest accompagné dun augmentation du risque hémorragique Pas dans le cas de PLATO

8 Les nouveaux effets secondaires découverts par PLATO: dyspnée,bradyarythmie,élévation créat, ac urique!!!!! CURE et Triton: pas de réduction de la mortalité globale, Ici réduction (mais étude non dimensionnée pour) mais effet très probable.

9 Is CURE a Cure for Acute Coronary Syndromes? Statistical Versus Clinical Signicance Editorial U Khot JACC 2002 These are not trivial risks. If clopidogrel is administered to 1,000 patients with ACS to prevent 15 nonfatal MIs, 10 additional patients develop major bleeding, 69 additional patients have minor bleeding, and 200 patients have surgical decisions complicated by its administration. In addition, 978 patients taking clopidogrel derive no signicant benet from this drug, and all of this occurs without saving one life.

10 Commentaires Essai relativement court: 1 an Dose de charge du Clopidogrel: 600 mg pout tous Reduction de linteraction potentielle avec lomeprazole Apects Pratiques potentiels Ticagrelor a utiliser en cas de chirugie très probable. Le s SCA en attente de chirurgie Prudence en cas dins respiratoire chronique, ins rénale?? Quid des patients à faible compliance potentielle ( essai thérapeutique vs vraie vie) Albert Schoming Editorial NEJM 2009, 361,11, 1108

11 Coagulation Cascade XI XIa IX IXa Xa II IIa (Thrombin) FibrinogenFibrin VIIIa Va VIIa + TFVII TF (Tissue Factor) X Rivaroxaban Extrinsic Pathway Intrinsic Pathway Gibson CM, AHA 2008 Dabigatran ATLAS

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15 Rely J Connolly NEJM Sept 2, 361 Editorial Can we rely on RELY B Gage NEJM Sept 2, 361

16 In patients with atrial fibrillation, warfarin prevents 64% of strokes. Despite clear and consistent recommendations, warfarin is prescribed to only two thirds of appropriate candidates After conversion to its active form,dabigatran competitively inhibits thrombin. The quality of warfarin management in RELY was assessed by measuring the percentage of time (excluding the first week of therapy) during which the INR was within the therapeutic range, which averaged 64%. (Similar to ACTIVE trial). RE-LY participants who were randomly assigned to receive warfarin would have needed to have an INR within the therapeutic range approximately 79% of the time to have a stroke rate as low as that in the group receiving 150 mg of dabigatran Connolly SJ, Pogue J, Eikelboom J, et al. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 2008;118:2029-37.

17 Dabigatran 150

18 Effets secondaires interactions In RE-LY, rates of dyspepsia (including abdominal pain) were elevated with dabigatran (11.8% in the 110-mg group and 11.3% in the 150-mg group). Dabigatran is not without important drug interactions P-glycoprotein inhibitors including verapamil, amiodarone, and especially quinidine Which dose for elderly patients, renal impairement (patients with CR cl less than 30ml/mn were excluded)

19 To prevent one nonhemorrhagic stroke, the number of patients who would need to be treated with dabigatran at a dose of 150 mg twice daily, rather than warfarin, is approximately 357. The rates of hemorrhagic stroke with the 110mg and 150-mg dabigatran doses (0.12% and 0.10%) were significantly lower than that with warfarin (0.38%).

20 http://www.coeurplus.fr