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
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.
BACKGROUND
Thrombin-antithrombin complex (nm) Thrombin generation in thrombosis 1,000 80 60 40 20 Initiation Priming Threshold of Amplification n=35 healthy volunteers 0 0 2 4 6 8 10 12 14 16 18 20 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;23:17-25. Coughlin S et al Thromb Haem 2001; 86: 298 307
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: 1381-1389, 2002)
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;170:1433-1441
triple -Therapy in pts. with Atrial Fibrillation after ACS or Elective Stent Implantation
ESC Guidelines in AF patients at moderate to high thromboembolic risk in whom OAC is required Low bleeding risk Elective BMS* VKA (INR 2.0-3.0) Elective DES (-olimus) Elective DES (paclitaxel) ACS + BMS/DES High bleeding risk** Elective BMS ACS + BMS 1 mo 6 mo 12 mo VKA (INR 2.0-2.5) + Clopidogrel (or ASA) VKA (INR 2.0-2.5) + ASA + Clopidogrel 1 mo 6 mo 12 mo 9 Adapted from Camm J et al. Eur Heart J 2010;31:2369-2429
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;4:522-534
Triple Therapy in Secondary Prevention after ACS with a NOAC added to DAPT
ATLAS-2 Studie (Rivaroxaban) Mega JL et al. Lancet 2009;374:29-38
ATLAS-2 Studie (Rivaroxaban) Mega JL et al. Lancet 2009;374:29-38
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 0.68 10.7% 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 = 63 12 0 12 24 12 Months Months Months 0 24 Rivaroxaban 2.5 mg BID NNT = 71 Rivaroxaban 2.5 mg BID NNT = 63 0 24 * 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.
ATLAS-2 Studie (Rivaroxaban) Mega JL et al. Lancet 2009;374:29-38
Should we skip aspirin?
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
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=0.36 95%CI[0.26-0.50] 0 30 60 90 120 180 270 365 Days n at risk: 284 210 194 186 181 173 159 140 279 253 244 241 241 236 226 208
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=0.60 95%CI[0.38-0.94] 0 30 60 90 120 180 270 365 Days n at risk: 284 272 270 266 261 252 242 223 279 276 273 270 266 263 258 234
PIONEER AF-PCI