Antiplatelet and Antithrombotics From clinical trials to guidelines

Transcription

1 Antiplatelet and Antithrombotics From clinical trials to guidelines Ashraf Reda, MD, FESC Prof and head of Cardiology Dep. Menofiya University Preisedent of EGYBAC Chairman of WGLVR

2 One of the big stories in 2011 RE-LY: Dabigatran ROCKET: Rivaroxaban ARISTOTLE: Apixaban Triology/TRITON : Prasugrel DISPERSE/PLATO: Ticagrelor CURRENT: Clopidogrel OASIS-5: Fomdapurinox HORAIZONS: Bivalurodin ATLAS: Rivaroxaban APPRAISE-2 Apixaban AF ACS/PCI Vit.K antagonist: Narrow therapeutic range Drug &food interaction Bleeding/ monotoring Clopidogrel resistance MACEs Stent thrombosis Variable response Drug-drug Dose/duration

3 AF

4 Recent anticoagulants: Mechanisms

5 Dabigatran A pro drug rapidly converted to active thrombin (IIa) inhibitor Independent on Cytochrome 450 Renally excreted 150 mg, 110 mg and 75 mg No monitoring

6 RE-LY : Dabigatran etexilate Inclusion criteria Patients with non-valvular atrial fibrillation (AF), at moderate to high risk of stroke, or systemic embolism with at least one additional risk factor previous ischemic stroke, TIA, or systemic embolism, left ventricular dysfunction, age >=75 years, age >=65 with either diabetes mellitus, history of coronary artery disease or hypertension 18,113 Pts with non valve. AF randomised to fixed dose Dabigatran without lab. monitoring Vs Warfarin ( INR 2-3) 110 and 150 mg dosages were tested Mean CHADS2 risk was mg bid showed 34% RR compared to Warfarin wit same bleeding risk (nearly eliminate stroke if against placebo) 110 mg BID was non inferior to warfarin with 20% RR in bleeding

7 Stroke Prevention in Atrial Fibrillation: ROCKET AF ROCKET AF: Rivaroxaban versus warfarin First direct Xa inhibitor Non inferior to warfarin with less bleeding Single dose despite short half life Risk of stroke on discontinuation No guideline for transition to other antithrombotics

8 Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation (ARISTOTLE) Apixaban vs. Warfarin in Patients With Atrial Fibrillation Direct xa inhibitor No lab. Monitoring Previously tested against Asp. In AF 5mg and 2.5 mg BID 18,201 Pts with non valvular AF N Engl J Med 2011;365: Compared to warfarin, apixaban reduced the risk of stroke or systemic embolization by 21%, major bleeding by 31%, and death from any cause by 11% in patients with AF.

9 ACC/AHA 2011 Focused Update Recommendation: New recommendation Class1 Dabigatran is useful as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with paroxysmal to permanent AF and risk factors for stroke or systemic embolization who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (creatinine clearance <15 ml/min) or advanced liver disease (impaired baseline clotting function) (3). (Level of Evidence: B) 150 mg twice daily with Crt. Clearance more than 30 ml/min 75 mg BID if ml/min For less than 15 ml/min? Net benefit better with high CHADS2 SCORE

10 ACS/PCI

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12 Antiplatelets

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14 Wiviott SD, Braunwald E, McCabe CH, et al. N Eng J Med 2007; 357: End point Cardiovascular death/mi/ stroke* TRITON-TIMI 38 results (ACS for PCI) Prasugrel (%) Clopidogrel (%) HR (95% CI) ( ) p <0.001 Cardiovascular death ( ) 0.31 Nonfatal MI ( ) Nonfatal stroke ( ) < Death from any cause ( ) 0.64 Urgent TVR ( ) Stent thrombosis ( ) Bleed requiring transfusion *Primary ( ) end point CABG-related TIMI major bleed b ( ) <0.001 <0.001 <0.001 <0.001

15 Prasugrel Better prevention of MI and stent thrombosis in ACS Pts under going PCI (More bleeding) For stent TH despite ASP/clopidogrel therapy High risk in the elderly and low body Wt. TRIOLOGY ACS ( high risk medically managed population

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17 Clopidogrel

18 PLATO: Patient disposition in the trial Ticagrelor Versus Clopidogrel in Patients With ST-Elevation Acute Coronary Syndromes Intended for Reperfusion With Primary Percutaneous Coronary Intervention A Platelet Inhibition and Patient Outcomes (PLATO) Trial Subgroup Analysis 7544 STEMI Steg P G et al. Circulation 2010;122: Copyright American Heart Association

19 Time-related Kaplan Meier estimates of the time to first occurrence of (A) the primary end point (incidence of MI, stroke, or vascular death; HR, 0.87; 95% CI, 0.75 to 1.01; P=0.07) and each of its components; B, cardiovascular death (HR, 0.83; 95% CI, Steg P G et al. Circulation 2010;122: Copyright American Heart Association

20 Time-related Kaplan Meier estimate for major bleeding according to the PLATO definition (HR, 0.98; 95% CI, 0.83 to 1.14; P=0.76). Steg P G et al. Circulation 2010;122: Copyright American Heart Association

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22 Glycoprotein (GP)IIb/IIIa blockers No routine up-stream For high risk PCI (+ve Troponin- Thrombus) and low bleeding risk

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24 ANTICOAGULANTS UFH LMWH Fondaparinox Bivalurodin

25 OASIS Fondaparinux 2.5 mg bid Vs Enopxarin 1mg/kg bid Pts wit ACS Non inferiority DBRT Same protective effect Significantly less bleeding with fondaparinux 2.2% compared to Enoxaparin 4,15

26 Bivalurudin: Main Results From HORIZONS-AMI Bonaca, M. P. et al. J Am Coll Cardiol 2009;54: Copyright 2009 American College of Cardiology Foundation. Restrictions may apply.

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28 One of the big stories in 2011 RE-LY: Dabigatran ROCKET: Rivaroxaban ARISTOTLE: Apixaban Triology/TRITON : Prasugrel DISPERSE/PLATO: Ticagrelor CURRENT: Clopidogrel OASIS-5: Fomdapurinox HORAIZONS: Bivalurodin ATLAS: Rivaroxaban APPRAISE-2 Apixaban AF ACS/PCI Vit.K antagonist: Narrow therapeutic range Drug &food interaction Bleeding/ monotoring Clopidogrel resistance MACEs Stent thrombosis Variable response Drug-drug Dose/duration

29 THANK YOU ASRAF REDA, MD, FESC