New Oral Anticoagulants and Other Updates. Tracy Minichiello, M.D. Associate Professor of Medicine Chief, SF VA Anticoagulation & Thrombosis Service

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1 Nw O Agu Oh U Ty Mh, M.D. A P M Ch, SF VA Agu & Thmb Sv I hv Du

2 C 65 y m wh HTN u u xm b AFIB. H m u ASA, m, ACE. H h m u. Wh gm w yu ugg k v? 1. ASA 2. ASA u g 3. W 4. Dbg 5. Rvxb NEW CHEST GUIDELINES AFIB CHADS2=0 hy (2B); CHADS 1 gu (1B); uub AC u +g h h (1B)

3 Nw O Agu W N qu mg My ug I wh h Rqum y Fuug INR h m Nw Ag N b g qu Fw ug Avy vm k ug M b Nw O Agu A, J. Hmgy Cygh 2010 Am Sy Hmgy. Cygh my y.

4 Nw O Agu Dbg Rvxb Axb (Px) (X) (Equ) Av Nvvu Nvvu 2012? u AFIB AFIB/DVT v MOA DTI X X R mbm 80% 30-60% 25% Nw O Ahmb Dbg Rvxb Axb (Px) (X) (/) T1/2 hu CYP3A4* -- Y Y GP Y Y -- A N N mg ECT, TT, PTT PT A X

5 RE-LY- DABIGATRAN v WARFARIN FOR STROKE PREVENTION IN AFIB Cy SJ. NEJM 2009 Oum Sk/SEE (1 E) Mj bg G bg I bg DABI 150 % y RE-LY Ru WARF % y RR (95% CI) * ( ) ( ) * ( ) * ( ) My (MI) ( ) *Sy g NNT NNH NNT=172 N/A NNH=204 NNT=227 N/A

6 ANALYSIS OF RELY TRIAL-TTR TTR <57% TTR 57-65% TTR 65-72% TTR >72% W, L 2010 Dbg :Dug I A ub - gy Iu my bg v (m), S Jh w AVOID Ihb u hy bg (m,,kz, qu) USE CAUTION / kz & CC u 75 mg w y

7 Rg C. 505 v 20% hm CVA g 80 Nw FDA Cmmu

8 MI/ACS wh Dbg RR 33% AR 0.27% Uh, K.. Ah I M 2012 Cygh my y. ROCKET AF- Rvxb v W AFIB 20mg QD N I w Mj bg m k & b k GI b CHADS TTR 55% N TTR y CVA wh bk w P MR. N Eg J M 2011

9 P S-Cu Dbg Hy GI bg-u u Ag > 80 Cm hy wh P-g hb A k u Pbm wh BID g Rvxb Hy GI bg-u u Cm hy wh P-g hb/cyp3a4 hb A k u C Yu yu wh w AFIB bg vxb bu h w b ub g INR w guy u h wk/v hu.

10 Sg Dbg/Rvxb B b-cbc, C, PTT/PT, LFTS P u-m gu Mg Ah Av -GI Bg/Sk +/-Lb Fw u 2 wk 1 mh 3 mh *u mhy hk Dbg :Pbg I I k v vvu AFIB 150 mg w y; 75 mg w y CC m/m CCL< 50 m/m. N mm CC< 15m/m Cu b bk hw Wh vg m w hy, u w bg wh h INR bw 2.0

11 Rvxb-Pbg I D 20 mg m CC> 50 m/m D 15 mg m CC 15-50m/m (bw CYP 34-, m vm, ) Wh m w vxb wh INR 3.0 Wh m vxb w g vxb, g g w gh C Whh g bg ) 66 y w/ AFIB, ESRD, y INR m wh TIA b) 66 yu wh AFIB & MVR ) 83 y 50 kg wm wh CRI (C C 30 m/m) wh w AFIB ) h bv

12 ARISTOTLE Axb vu W P wh A Fb Chh B. Gg, M.D., Jh H. Ax, M.D., M.H.S., Jh J.V. MMuy, M.D., R D. L, M.D., Ph.D., E M. Hyk, M.D., M.P.H., Mh H, M.D., Hu R. A-Kh, Ph.D., Jk A, M.D., D A, M.D., Av Avzum, M.D., Ph.D., M. C Bh, M.D., R Dz, M.D., J. D E, M.D., Ju A. Ezkwz, M.B., B.Ch., Gg Fk, M.D., Dv G, M.D., Mg G, Ph.D., B J. Gh, M.D., Sgy Gy, M.D., Ph.D., Shy G, M.D., A G. Hm, M.D., S H. Hh, M.D., Jh Hwz, M.D., Pu Mh, M.D., Ph.D., P Jky, M.D., B S. Lw, M.D., J Lu Lz-S, M.D., Pm P, M.D., Ax Pkhmk, M.D., Fk W.A. Vhug, M.D., Ph.D., Ju Zhu, M.D., L W, M.D., Ph.D., h ARISTOTLE Cmm Ivg Gg CB, N Eg J M Smb 15, 2011 ARISTOTLE: APIXABAN V WARFARIN AFIB k 21% 5mg BID 20% CVA mj b 13% h 11%* Gg CB. N Eg J M 2011.

13 Th Th W Th Nw Cm v W- Sk k DABIGATRAN RIVAROXABAN APIXABAN X X INTRACRANIAL BLEED X X X MORTALITY X X X** BLEEDING GI bg GI bg y u DRUG INTERACTIONS L-GP G & CYP3A4 CYP 3A4 NUISANCE S 10-20% y DOSING BID QD BID METABOLISM 80% RENAL 60% RENAL 25% RENAL AFIB TREATMENT COST y mh u w < 20 $80* $960 bg $ $260 ~$3000 vxb $8.00 $260 ~$3000

14 Au VTE Tm T Nm Dug Y Pubh Ov wh h/lmwh HR: Ru VTE v. w (95% CI) HR: Mj Bg v. w (95% CI) RE COVER (DVT / PE) b 2009 Y 1.10 ( ) 0.82 ( ) RE COVER II b ONGOING EINSTEIN DVT v 2010 N 0.68 ( ) 0.65 ( ) EINSTEIN PE v 2012 N 1.12 ( ) 0.49 ( ) Shum S NEJM 2009; E Ivg NEJM 2010 & NEJM 2012 EINSTEIN-Rvx Symm DVT V 2.1% vx 3% w Th EINSTEIN Ivg. N Eg J M 2010;363: V 1.3% vx 7.1% b DVTby 82% M b 5.4% v 1.2% Cy SJ NEJM 2011

15 Ky D Dbg D hmb hb Tk w y 5 y (.g. LMWH) m Rvxb D FX hb Tk w y 3 wk, h y C b u mhy

16 C Yu bg m yu h h hvg hymy u h u hy x wk. H w kw wh h hu h bg. R Fu Dbg-Pv Mgm 1/2 Pu wh k bg (m--m u gu ugy) Pu wh hgh* k bg ( mm u gu ugy) P- CC >50 m/m CC m/m S bg 1 y b u (Tk 2 y b u) S bg 2 y b u (Tk 3 y b u) S bg 2 4 y b u (Tk 3 5 y b u) S bg 3 4 y b u (Tk 4 5 y b u) P- ( ) / C umg hy h g vy wh hm h b hv, g bg k u h hmbmb k V Ry Thmb Hm 2010; Duk Cu Phm Dg 2010

17 P- P R Fu Nm m mm (CC >50 m/m) M mm (CC m/m) Rvxb Pv Mgm H- L (hu ) y Ay u qug u gu S vxb 1 y b u (Tk 2 y b u) S vxb 2 y b u (Tk 3 y b u) ( ) / C umg hy h g vy wh hm h b hv, g bg k u h hmbmb k C A 65 y m wh hy HTN hym m wh w PE. H ASA. H LMWH bg w.yu A) h w h h w u k bg B) u ASA my hyx

18 Rk Bg Wh Sg, Du, T Thy Wh W, A, Cg P Wh A F w + = 2x w + + g=3x H M. Ah I M D w: 10/21/2012 NEW CHEST GUIDELINES CHEST 2012 F kg w w ugg AVOIDING m hy x wh b ky b g h hm: vv, ACS,, CABG (2C)

19 CASE A 55 y m wh PMHx w g wh PE 3 mh g, wh LMWH w. H h h bg m hu. H wk u uvg. C Hw g wu yu mm h y gu? ) 3 mh b) 6 mh ) 12 mh ) y

20 Rk VTE Ru A C VTE Rk 1 y Nx 5 y D DVT 3% (6%) <10% Mj 3% 10% M 5-6% 15% Uvk A 10% 30% Ru > 10% > 30% K, B 2005 Gu Du Agu VTE I 8h ACCP gu 2012 AHA 2010 ASH mm 2008 F VTE y k 3 mh (G 1B). 3 mh (C I Lv A) 3 mh F h (uvk) VTE A 3 mh, g-m m k/b k (G 2B). A 6 mh, (C I Lv A) 6 mh Ru VTE Lg m (G 1B). I C I Lv A). Lg m APLS, AT y u K CHEST u Fb 2012;J Cu 2011; Bumux H Hmgy 2009

21 C kh y u D ( v hmb) Lw k u/pe Pxm- y 5 u k v PE v. DVT P g wh PE 3x m ky u u PE h h g wh DVT Bg T J Thmb Hm Mgm T Ug D-m Ru Dm Du Agu P G. N Eg J M 2006 Duk A I M 2010 Sym Rvw D-m + 8.9% D-m 3.5%

22 C D Ru C Lg w hygm 5-7 m v D-m >250 ug/l AC BMI >30kg/m2 Ag> 65 Fm wh 0-1 k h u k 1.6%: 2 = 14% Rg CMAJ Augu 2008 Im Thmbh Ru Rk P gu Ru VTE Y 2.6% 1 hmbh 2.5% I VTE vk 1.8% I VTE uvk 3.3% Uvk wh hmbh 3.4% Uvk whu hmbh Ch JAMA % Shum Am j M 1998

23 Ivu Bg Rk Agu Bg Rk F Ag > 75 Pvu GI b wh vb u Pvu b w R/h u A hy C A I M 2010 A Pv Ru VTE. Ru VTE ASA 6.6% Pb 11.2 % VTE 40% N mj bg B C. N Eg J M 2012

24 Du Agu Uvk VTE g k C x ( P E, m, h m b h ) D u : C u : < 1 g u u D - m 3 0 y, w k I v R g x R V O C u g u U / S 3 m I b g k h g h A C 3 m h IF DVT G u/ mu -m. I - m u u AC g k C x ( P E, m, h m b h ) D u : C u : < 1 g u u D - m 3 0 y, w k I v R g x R V O C u g u U / S 3 m I b g k h g h A C 3 m h IF DVT G u/ mu -m. I - m u u AC PTS D-m Bm > 30 Ag > 65 C ASA gu

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