Antithrombotic therapy in the ACS patient with atrial fibrillation

Transcription

1 Antithrombotic therapy in the ACS patient with atrial fibrillation Kurt Huber, MD, FESC, FACC, FAHA 3 rd Medical Department Cardiology & Emergency Medicine Wilhelminenhospital Vienna, Austria Great Minds, May 31 & June 1, 2013

2 Disclosures DISCLOSURE STATEMENT OF FINANCIAL INTEREST Kurt Huber, MD, FESC, FACC Research Grants from Bristol-Myers Squibb, Eli Lilly, Medtronic, Sanofi-Aventis Consulting Fees from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Fibrex, Eli Lilly, Portola, Sanofi-Aventis, Schering-Plough, The Medicines Company Lecture Fees from AstraZeneca, Boehringer-Ingelheim, Boston Scientific, Bristol- Myers Squibb, Cordis / Johnson&Johnson, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, and Sanofi-Aventis.

3 BACKGROUND

4 Thrombin-antithrombin complex (nm) Thrombin generation in thrombosis 1, Initiation Priming Threshold of Amplification n=35 healthy volunteers Time (min) Thrombin activated during initiation phase is only used for platelet activation in the priming phase. Platelets in the Priming Phase are almost exclusively activated by 4 trombin induced during the initiation phase Adapted with permission from Mann K et al. Arterioscler Thromb Vasc Biol. 2003;23: Coughlin S et al Thromb Haem 2001; 86:

5 Cell-based model of coagulation Initiation Priming Propagation vwf X VIIa Xa Va Xa TF Tissue Factor bearing cell TF VIIa II IIa XI IIa V XIa Va XIa VIII/vWF Platelet VIIIa VIIIa Va IX XIa IXa X II VIIIa IXa Va Xa activated Platelet IIa IX IXa activated Platelet (mod. after Monroe et al., Arterioscler Thromb Vasc Biol, 22: , 2002)

6 Major Bleeding* per Year Odds Ratios 4 3,5 3 2,5 2 1,5 1 0,5 VKA ASA Clopi ASA+Clopi VKA+ASA VKA+Clopi Triple 0 VKA * non-fatal and fatal Hansen et al. Arch Intern Med 2010;170:

7 triple -Therapy in pts. with Atrial Fibrillation after ACS or Elective Stent Implantation

8 ESC Guidelines in AF patients at moderate to high thromboembolic risk in whom OAC is required Low bleeding risk Elective BMS* VKA (INR ) Elective DES (-olimus) Elective DES (paclitaxel) ACS + BMS/DES High bleeding risk** Elective BMS ACS + BMS 1 mo 6 mo 12 mo VKA (INR ) + Clopidogrel (or ASA) VKA (INR ) + ASA + Clopidogrel 1 mo 6 mo 12 mo 9 Adapted from Camm J et al. Eur Heart J 2010;31:

9 A North-American consensus document on antithrombotic therapy in AF patients and a coronary stent with moderate/high stroke risk (CHADS 2 2) Low stent thrombosis risk and low bleeding risk BMS DES High stent thrombosis risk and low bleeding risk BMS DES 1 mo 6 mo 12 mo VKA VKA + Clopidogrel (or ASA) VKA + ASA + Clopidogrel 1 mo 6 mo 12 mo Any stent thrombosis risk and high bleeding risk BMS DES NOT RECOMMENDED 1 mo 6 mo 12 mo Dabigatran 2x100 mg was discussed for the first time as possible replacement of VKAs 10 Adapted from Faxon DP. Circ Cardiovasc Interv 2011;4:

10 Triple Therapy in Secondary Prevention after ACS with a NOAC added to DAPT

11 ATLAS-2 Studie (Rivaroxaban) Mega JL et al. Lancet 2009;374:29-38

12 ATLAS-2 Studie (Rivaroxaban) Mega JL et al. Lancet 2009;374:29-38

13 Estimated Cumulative incidence (%) PRIMARY EFFICACY ENDPOINT*: 2.5 mg PO BID 12% CV Death / MI / Stroke* HR 0.84 mitt p=0.020 ITT p=0.007 Cardiovascular Death 5% 5% Placebo HR 0.66 HR % 9.1% mitt p=0.002 ITT p=0.005 Placebo 4.1% 2.7% All Cause Death mitt p=0.002 ITT p=0.004 Placebo 4.5% 2.9% Rivaroxaban 2.5 mg BID NNT = Months Months Months 0 24 Rivaroxaban 2.5 mg BID NNT = 71 Rivaroxaban 2.5 mg BID NNT = * First occurrence of cardiovascular death, MI, stroke (ischemic, hemorrhagic, and uncertain) as adjudicated by the CEC across thienopyridine use strata Two year Kaplan-Meier estimates, HR and 95% confidence interval estimates from Cox model stratified by thienopyridine use are provided per mitt approach; Stratified log-rank p-values are provided for both mitt and ITT approaches; NNT=Number needed to treat.

14 ATLAS-2 Studie (Rivaroxaban) Mega JL et al. Lancet 2009;374:29-38

15 Should we skip aspirin?

16 WOEST WOEST Trial - Study Design 1:1 Randomisation: Double therapy group: OAC + 75mg Clopidogrel qd Triple therapy group OAC + 75mg Clopidogrel qd + 80mg Aspirin qd 1 month minimum after BMS 1 year after DES 1 month minimum after BMS 1 year after DES Follow up: 1 year Primary Endpoint: The occurence of all bleeding events (TIMI criteria) Secondary Endpoints: - Combination of stroke, death, myocardial infarction, stent thrombosis and target vessel revascularisation - All individual components of primary and secondary endpoints

17 Cumulative incidence of bleeding WOEST Primary Endpoint: Total number of bleeding events (TIMI criteria) 50 % Triple therapy group Double therapy group 44.9% 40 % 30 % 20 % 19.5% 10 % 0 % p<0.001 HR= %CI[ ] Days n at risk:

18 Cumulative incidence WOEST Secondary Endpoint (Death, MI,TVR, Stroke, ST) 20 % Triple therapy group Double therapy group 17.7% 15 % 11.3% 10 % 5 % 0 % p=0.025 HR= %CI[ ] Days n at risk:

19 PIONEER AF-PCI

20