%PDF-1.5 % 7 0 obj << /Type /Page /Parent 1 0 R /LastModified (D:20181219063101+01'00') /Resources 2 0 R /MediaBox [0.000000 0.000000 595.276000 841.890000] /CropBox [0.000000 0.000000 595.276000 841.890000] /BleedBox [0.000000 0.000000 595.276000 841.890000] /TrimBox [0.000000 0.000000 595.276000 841.890000] /ArtBox [0.000000 0.000000 595.276000 841.890000] /Contents 8 0 R /Rotate 0 /Group << /Type /Group /S /Transparency /CS /DeviceRGB >> /PZ 1 >> endobj 8 0 obj <> stream xZnF}W tCű]B Ú\ћRSTufŢM+,"ERsf朙YNo܀ /LOى38>>BU3zTK_|Ϧx۱ʾxs-]΢gtxK^;ށ }/0LcxL_^_ GYw^ {ƺ~e瑒Y|taEfR4eBI,ׂLFW$C\,ğ\=B@, ^MMg3١y3+೙X21Q<gL +I6{N~h1kg!nh&nI㷡C |]VjJH56 ztTI يk.xc]2yqĶ"G~eX_KlɄH%aҥJ^unT:#F¥_TD٤K2|$㑒A1{ŹݷЁ1>0L )}R *UIL2B )͒ kT  "b ' CixmU^ 9_k@%&~+]{hYXkY+]n -R8pzZN^ T,G%_E^ B׳Ƹ^ ‘3' l?uX5OvU0D3Wr]V v&U>zncRVMX&QZ]v6ƶlhA϶gtQC M)3o q. n#cRfx6EisQ(83+PONt{,/Pmْ/T?VrN,jD4WRej>6,-*PFTΤ)Š4R)/`Ts!L;!XZ:MxDIܷR\DD"*%8tc|Hܠ11B[ N# c#FWq=Cc2,Iʱ*7nP|peQ C:@Ke,\14T8QM:42ժ 7ؘdmdĪb`V31M;&K 1;I$Q0.ybbCoJԭm~YdLexC*} 3Kr( ے@4hrUHfxڮ`e0-*p2\<T"Jm$Ys5K1!*` 4踽5//q͇*xMd*%"Z 0,|C{69LHe]H# 2Gp7RSze5!g,%HeTmֶ/vШY+ޢLl_㱱jBKeKg[:0h`:Wg$ym6"d^I7R#Ozd_/̿' endstream endobj 9 0 obj << /Type /Page /Parent 1 0 R /LastModified (D:20181219063101+01'00') /Resources 2 0 R /MediaBox [0.000000 0.000000 595.276000 841.890000] /CropBox [0.000000 0.000000 595.276000 841.890000] /BleedBox [0.000000 0.000000 595.276000 841.890000] /TrimBox [0.000000 0.000000 595.276000 841.890000] /ArtBox [0.000000 0.000000 595.276000 841.890000] /Contents 10 0 R /Rotate 0 /Group << /Type /Group /S /Transparency /CS /DeviceRGB >> /PZ 1 >> endobj 10 0 obj <> stream x[r}Wtv%@cK^yD;a q 5_BrzfDd)p>woxHϞ'gϱGOsd@z|A )v D=Y) o=qǤx=~o_'}LFxKl{w~08Ѵ q8yJ>^|sad@ZQHRJZJ.JJQ<{U%WJRW.5 8:5eةZD\U8Eēh?B4-$\xQ 2Քk WJAKiX2czpw{?8$OJ+ \~oE2]InΉz c Q7FCW/c"Lt3M7/_t/ x7L$=7Zfri FW%$HLc &ztV+xVT4(jT%f}npھW|܎VCu@=n"mqӵ2IrU&`$Q&WԶ,տIF +H\ٝdq Ld1P b' |^¡59f! k, AruUljqۚ %>:L:tZY2}_|(29X kSjdn['zRz~gI۽Bڼ񓨌 .8bTڬn7+ps 4욝Z-um_֜@7TMAGq0"Ѡ4%FAܴg48+"Ua5 Y,,oݫ=؂A34 =ECR NY5pR](Hk /Q4 Td v% dHO¼UsqC':.Q`l|Dm1|gРۜ]RBxxjD~yf_v'I?D=(ѰG?.UB68 N8fg?g4fcFO/A/dW `BnB "Q 8NxP5yQQP2lLhwlrnetwcL8IÔJFr99?e8͹ / 8xjem/gBtkV>nZi5Jöp!zvjmѸomGȉ$oRw7\ Gfv܈F%:؜=26!&!;@S%mҪG U$/%Kx[;/?7m/vȑO{ƈP5.j/5 G_6p@zxSYf%7=D}z{݇Ȼط7ǎS[rV%J 9im j`X-,W[Ճwk)OlMz}rtR +ZU7w2Mʳ y2{li 9Ot%xL+~Mw^e[.ueo0HSW>bU)O @wĜ?|E{x.ٛ9W/OO+m~&E@ޛsz(:,轪5%Wy|#v{xni6 ];ųڻuV֭%&܇$J陼ubQnM endstream endobj 11 0 obj << /Type /Page /Parent 1 0 R /LastModified (D:20181219063101+01'00') /Resources 2 0 R /MediaBox [0.000000 0.000000 595.276000 841.890000] /CropBox [0.000000 0.000000 595.276000 841.890000] /BleedBox [0.000000 0.000000 595.276000 841.890000] /TrimBox [0.000000 0.000000 595.276000 841.890000] /ArtBox [0.000000 0.000000 595.276000 841.890000] /Contents 12 0 R /Rotate 0 /Group << /Type /Group /S /Transparency /CS /DeviceRGB >> /Annots [ 6 0 R ] /PZ 1 >> endobj 12 0 obj <> stream xY]s8}ϯoMfj6MLm¤K郐QVH,M~^24;Y:,#!${vo І߰HjW*KU{2(9h>%l7޽G5Qv5tZ}ứօe%]'7W>\(|`[n_Sm3KeSh[IYNz˂poDpN$e&Q S"K3VbX@XrbX KnXVc%}䣽ϻ H:]ĬI/g,PT!'IÁ*s,S:RIC[kl玢kht"/J- U0) Hl/^91br~z"9XfK0ϽیKN\I{JNH_0iHrOJbb%À5:'ѡ!QSL0GELrf9ҮwNTһ'DCh4GE梶 uiOsJ }KxyI8a]gt^0DDPIZXC5 MSZ+_ZvA.sre1dÉ,(A69 ^HSɡ O X*a4{QR!Jt,&!jJ 6)it^=q=p_DVرSQ ,xb%lI٫1»'ad,UYk4+)xaO Fْa,pJfdIP!{\dp8O`?ou9Bx3cȢ)Z628նxa,0sH> endobj 3 0 obj <> endobj 4 0 obj <> endobj 5 0 obj <> endobj 13 0 obj <> stream JFIFHHC   %# , #&')*)-0-(0%()(C   (((((((((((((((((((((((((((((((((((((((((((((((((((O  !1AQaq"2BRr#34Cb$5TcDS7UstA!1AQ"aq#23RBr$Sb45 ?P @(P *$T؁PH P (@(P @(P @(ž OAZ=xV:թЇ%oFݧ[䠕\A=:Y5C46zjK.܃_,{-[dDI8q4r &; I=LRN;[@ڷ[܉"6@QڱURKe][y(z"S3&~c(.~:~2I8gCKrvȫyw:aP @(P @(P @( GNtɐų4뼡 gW!j8Ρj=|K7Qb5^M N\!uyW1ӈg>[/0ܬSVAحpԖᑕ]V$J۹u9XCӚf(^wT kW/^[BIy/8Jիx&NrWX5Y/M(6g]ϋt"-UeTM:\JEi+#qZb߻?3\j[#zHxkʲru223m5W1j2Syi:.쯶ۨI=[ qYig=7K;ė-(W~KOܛge21Xu;@=gB5^E-U˙ 즕轉j?:x8 ;QeƷ %'؅W'/-InӫOkb8h[BG;Λ+Q[rD P3Y>J^hi5t})4.8sxTWևEG1A^3~ϪܒP"RJpq"1Yul?A+4]aJ5{-Ϲ7#dW<큧.#%V 0r:W_T/Rnx} ADvջBjf@(P @(P @( pU*}6IW@X18ᠧ-۲][ˇwkT7:*ud4 ÏKe$\nW,v."e]<?b2RtmWi,?y )i$d&1Qu_>HץM|1&tPCt9)\V3؀29*_2U|]NJ:mٳgЭ~X@p5_f[\- TF2M7+5ɐjAR=šrE;6xkzV +s4J DUTdvJ@(P @(P @*A`iwM~fE[1i|_\siЋoKOwıYJ[k#:$5d [4;T +NQoߙM<šE[]eåLCp¤+ה+9][{w}5-pH oͶWۡjta:U&"8㬜ȧ9GuUf8JuQ^24s9 Ds +mٮ\~YRy^1+̞? l27O93îWis>Iš㇅IRpJjBI\K}݊'[qVV5j^h]qq=SIMӯBadG nqX8xq Ko7w/zD<ǻ"|,msW_I HRy]SSEP @(P @(@9<{˾ GZ~\W⸊/G-i/UMU/7e9HzWL)$GjX.m ?>0>=j;Z*_]{N¾lvE?V澇 ?,P~ߧȧţ!6[+6ëC|< k9bhq]^׾bεT]7F qIa<=JCdNO~;*haN6z]6_u. #~|RUd~osu#=(\FG ҍR\OF 0+7z;KAV=&Ԋ\YìM |~PqI)WjPQz-<>/Mjigk]8S͠6 S.CdU[x$k~+9U< j յ-V{n5oqHYCkX xG"F쫧U.wAFyb/3@Gu1n%'g.qt$".ujUGG=Yw2*v~g29aa~Ed}Kε-ŷQutT4('y @(P @(P\+tC.&Utv xlN1\v]JsOI>Y5dX'u kR>l0[S6T5(ÆWՊ_BjT*k]Rvr \%;wPMs͗thFA%=QH'ξ˗0Х{N₤99KFZݧNq#Kv}T8|*l .()ǝfXg);3`DcGGw;ŝ9_ƲÄk,\Vr$reYh,8)Euʘ|jR$\3ϡKj* fb<Qi= +_֥-mne.99Y7(g{lpUY:oU&ױm[_KT)#H jJU(c's.UVSKTWCwͱ2}oynEkEG.<P{=qq",') ݝi^ILa'Vyt}_d(׶N7g^·ʖB-xFWMȗ h/%uiUPR0{B3N+L냽 wW%/'ޯԗK%TX\Yrc80qWTҚW>N_&ד>t\ -mu kimxU~%dJrտjޟ^ρ<7Sl~z3-&:^6Lޥ}Ƣs~UP=edS3Ʀ%jk&JaҗסsQʟB\ Ҍ 5aF曊9LFZRRUÉpzdtJ@ H%C' Hel$!ۋ֫x?Ԙ6⒗ 7HqDjKf/'&rHDze(xKeHVP XK$EڲH=}tO^Ay$u@t!)RU~{ ܌\H訸BvIy+-ɵٮ$Bq1TFFF.qfYN1ѳR$y%"4($Z-)nC$ `c;Jcկޝ`[Ux~TZm98R܁^c83ʩ ;&Htᤠ9@&6Sg||מ$ٖyR:^(Zֻ5nYqMmI&#,5q\4Q;;vuےiӑ9UܨJ @(P @(P @ZQ̎èX<5 ]L:k|xf*8jUUuWmRF36ji_إ*IV<<Ʀo%: Tn-{!_)h("P gl+$n劉J< w\>KHyZ9s%ꛪe88#z F68)KkPDVJt+dm^W\mGNDStjIgLΙc!ƍouQI[)8RԢ|yNqⒻf 4lqWꋄ 佻oXZUœz j4bwgS.s쨳ZAP#P|l٫„TuՖoGrVCbml'BaPq3ـ5V[+]a65Ξa nkB s{NO\9:oO]䀹%M^`B$<Go3=# ~lف]ToBǤr먮R"h)Y )#+4F [+InweQܺ$bt^}89‡UkGUխ*}U7027#az/שO$1[3PP @(P @(6\tXe#ݝ%P )SaOµzN81ctϟ Z1.)]b\`] ;=RMX[&w!finv[< &ۗ&d() žyc#/PyKFk䛖3/H\sp`y#9omzЅ,.R!Te|KeDv#~[]>tqtjE6M~A*,‘dl9e֌*R:Z^cؚ8ӓnd'|6ӲZ*D:NSJo>Yz TOv6UO\d:Ħt2r}nR1ú"*5¬ѿ`lKL?% :/.%ONTTC8̨7ޭen YїٚVtVېǗ尯m`\qJjjJJj:k4;גZYi!@}d`}Fʭxn:+uFtΦ"u^g4YpI l+:Ÿqjz96xfqz6ږnd$Rm (p׺zxۅFln^L*rmr>N~QD!:L$!L@]$=V??R빴iũq=kݭ|5WF~C#ь h($9`Te8x%ĤqJWu>l#5)FCN:@qe<vVjY \Iʹcn}Hvomv4d#~KeAZzV>5.+1v\7,j%C[~RP`hmJ9)#* P8N=ԚPp\)6ZvZOVwy]rS)iqoh!g W,ИIF/Y6ZjW\; E zΫ)sq@f4}Lc8]8> T@(P @(P @(oGco5GSF $v sU*b$ܣ(\--=w=Ғ&So6FZ_vKRݵCikWm A!A\K+=P7' Y/Jmjբ~mzV߹헊L~EP\fiZַ[RB8G!c'b:c;Yn9pQRj $$] 6{[Wn-kkO?)-_'eۛe(j:{wRT!K FWxm,S^*JWrKEÅ4.yn-8-"M7liWsRܔKd=Vc9;.aGNnDUDVm[KSqkFMCm7-lu*([8,5XГtӌAɩFɹ7gշ⤵>OćlO߳1q15%;yPVm>%'Rs u.)IJT7(ZD[n XڴHuNF Wdq,!-$|"&'\u*Nj/qA(Ky&ĹSP=}3fkkj# [}b%8V(r*RV\*PM^WKF벒KuGQȷ\FulD[}+X m[eT+7_vY롇Q*UݮKY&cHYHÜH.6Q֯ q9g2:۬9]6|My3ᆤӪqp8p!򕕍8iT€P @(P @(P @($t9 #\$)')bhάgcjur7N/XA'2r$(ר2ْhRl$|ђ{6SR4)K>j8JM-lq(QR+ȉݔ_K! _`ԓ2[jYA3ygjt>^'/4)5>ק[sք7&*Gnx\NEQTѫRҊm?\0Wj2]Shݳk,qu)[Gxνd<{tf^[1fE\.?ӹujP0a1^#5.Ҽ/B..]Y&e[FP9$5U*sxS$(Ε:JX?cO[5}l5y˟Ie~իt}}YVW|B @(P @(P @(P @v4'u0 gw?5]浱XΓvM_[ N9.x>eh@LVpjV;<fceU:>Ml/b58&{>^ (T \~ʕɸ5ӿN]/q.RjSrP(kG">?8TO ^_r̂uWُNoǢFrD:xu6|OَY^R{0(EY-~+7[lul9ŠW&Ee\pT}_6j(P @(P @(P @(ڵ%g"e1%CpT9)>bqDx&2w-/`ޢ:dě!O2Z;{;|5zkMϚr}̺Ֆ*\]okqCnHTϬUbha7w.vد Ouڶo,k;m"qSe}Z#!?3Մi8m01sP{JV|Uۣ(-qZU8VX[h%>8  6?0(؍VP @(P @(P @(P @( KQRG!;4svZ0<*чf/ܸj?؛ŠHɏ 2y!o3jIT|SwgAJ)G8:}Q$|SWxe?GƗ\R}Kmv 2)i Riߟ\|5{R>ƿosELn~xWU!Ɂ!cO[e}U`J#$V-=ҩu`Nǐy 8Ći-ujET^jk$v%>g 1]POgUҕ+veU>6!ZSLFg!Q1Uq^E K ^+C`w0W{ WMiב]2ǯEj9`[VJ뫷m]/o.<b =>⍀a[SF_MjKxc8{'ic>al8;ĺtHvBFE歄g ?Ѹp8>uY'z%K7){RiVd1z=<_1r<*`LJ?:QЩ57Ekw5o`"JGW8>}'J=׃4FP+եMN!mZJTRwҦRZZbBEP @(P @(Pm ۏC~WXlWw}6_ET\+航SqjRYʖ(yղYlT=]ެP@( )!I)P Iԭ _re:DXw>!g@m9UEd\eEz[?$*Ro[rpg~i&~QkZ7ZnSFfӖBE o C,o9bpNy=~;dΌ&PK9'tln#J!a^^R 굏j(Esq*+nqdC?G!|fz5!(J/VBEP @(P @()##~Ctur? n"hI? ӭa)_jnl=ے[~ rRkHG쪺ٽG(Z55iqwlڒhqXj 1xs~Vu_I]Ԩ’.Vy$.v2Y#ˏda{9(28-S 5NE.#8=(יqku:N-EJ>VJ+*˻B&'v5$ (’!;SkbNt~3-ݡ`ܥG75CwS^]{cg} iHU 8?a_|+x(Gu[ Le|FfFTKVW6d6?UU*/YJN/d#2tMfLS~T$>/Font <>/ExtGState <>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI ] >>/Group <> /Length 848 >> stream xWmO0^c$H (똆AIC|J(ՠemIªل׹Gdw7>9<GkDžaW$<"H2|R(29:9$^-e>..y.Gd:|VCd` ')ɮB(TEҒ %% E֙ J,$BDO&D>MH0-6=C.h&CfR\ X+b :Nic*k+ p.}&xs|"8 n,v )W-6o=߸hNftK:M[ۀr!e\KeAky$RP<⺍pxup8>H  M{qI3_w,縲eGfNՑmna.hȓjYU,b\2OuyZ6#sC͚3gkriӲ ly#4]kDfu |w*lm O镸080iIsӵһ%7/i\XJ.̚5K5jM9aq'wqh%Q*i gyQ(p]5'CԫkSuRCln_*9{.+|FAqp-Pg*O hsRՎSJ&`1U$GBHB-K5NюG~?Rh#%SkC3a-r"7αը $O endstream endobj 21 0 obj <>/Font <>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI ] >>/Group <> /Length 219 >> stream x]M0E$MG "څJ6M,:Ãۼ{cb["Y.iFgTT&IF |Sk=`+W^|Ug'~5|h)]"u$F ˔4S)\%hPra~doU%]0 +5St*ӂ>6|OɄzU_[I; endstream endobj 15 0 obj <>stream JFIF``C    $.' ",#(7),01444'9=82<.342C  2!!22222222222222222222222222222222222222222222222222bb" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( *kZ= )՘W5mZx?sS)(rbzz.-+E_|dF>g?qZP ]3N'K:?ƸT/.\$s1c 'j9W᭏=Mrķsݓ@aGrZ}{R}NՋHf?^d!,.@#VnZ)BJPG i6ב9O?0H\kǝףG1>X;} ExM_@eZ}H2Bo_U a1Jr˺-aUL cZݫ L7YSG/k?oo\jSѫV]֙宙>bx.2)YWN/XޑxVRr{W\֡p~Z7gS憌#ˌ5JOkT{Y$9$5b'JAI a}%hT(((kH0zVBEY[RI(GJ?zӉ[?kFniE?D;o l_DP^Xž "Lh?g |{עW|mIW̗ɏL,WQCz-Wv\@He@єRWWTV.⤂( ( ( ( ( ( ( ( ( ( ( ( ( ziSs('*:e>#j\!eG9_Ɍ-/S#N_GxA'4?2+><(niv%Lp?aG2_Iѽ~kNe>XՂ (((((F`Y I=c9ũՍ0}E $=M ||?hjz#59½OC+oEQEQEQEQEQEQEQEQEQEQEQEQEW;65(jnm;<>/sW~ʯT4bXZJy UEYk (;QEIaEPEPYֳmX5,x0yvmwĶZDH[>X>Uծ{ƹ|EQPz^*ϚzG<\7.7y^V/ԯe}Hr}~SZs;p } J*:ӟ4lNHcfF q*<%s] o,z'eд ( ( ( ( ( ( ( ( ( ( ( ( ( +h[TělOSa )CV &8ş#im ҺkIT׆>+)lݶ~^ s_QJT~΢7ȩk>l]GȮϟekYx^=+Spߊ\5l5*F\u|+)[˧{%{|=?Z5o^݆1i~r?5Q]r4ڻUfԜ?t=*ߔ<3cVoĒkN_Wr>ʍ?g+P(((((((((((((߄a~*^Ù-e?އ?_5/e(H+ωOMUM^%t ;{cb3 cuV`k8 s\j=KtquV s^d|':d4sYP:մg:M訄y+E3Q@rLPw܁ޕ#Iifu˫梹k j%#a[a{vX5 <]/.Ѱ(vO},: q̧0cw>g`p IQ^QQ@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@g..-55\%ʯwG^ Yٵ;V's[ӭ}]U-5;Gr`:'KG9k!W]򥾣Z1_k|CJ}9[ϗo?לj^n4學W/#{l[%вEK]Ha*AsΖQ^ZNƿsҎq,: oY杦sZ/~u2IO~?.e_XsX?k*?2G}%pƹ&=K!..;QGonZ/ i4(|<կ'Ov/`OW (((((((((((((((<2"V`)\>|v08 Z( ( ( +7YcSFڇc65Mťvnɕ/4;P+_Nc,b=MNQى/ts)QПkRú.A,`aѣE?MD : nލPcϢ5-AAEPExK֧O`-a9?iKa9$osN(0(((((((((((z+qBԃTs\q [3kG|?wwXEu2դB)Mj὜6R~j6dTFLr@ bWW9]،EJxYۡÇNxxt8+z$oR>V>VNj|=i1}j$|$|t7WDx%y"E:9/ \ PI4A({U~ Z;u՛!/+s%K1 @A#k>X;CUB]TU88s-wrpq~j ;ƻnŧ H\4`N΀XzYTs)ՔtI)bH5K ,RFQ2l{&o~,fl;|Aj~)XeزE PsʁV<mw[iOl#dP ޠnNsZBp7i}pI$Js6qnD1ykZ<:ڹcԓ'T&*mNYQT18J^)jkoEe [xZfm,Y@Ԍ m:/Ŧ<.مP;zV?~6ݶy ޹U9B&TeOI껛V 4jTFN `Ӯr+GP%_VFBI( Z|%]Z-C;bn8 GB+v-A𦩨뗷r2z8JrSV۶2ԋ$~д}14Ni^#K! D, O@NzWH%Kkw* B2O%{w?ABӯ{i Ȇ(@3d凄\ݕLqz>-6y jp>?|aP>?9j? C|XehmQ (8C\F|µ 'kt♜k OkhS bSyp0Y[\!<yj3EqO $R(du9 Ba"։.co2g夑8?s׍ëw17Ṿ; Q\:}$_;{=SOGXUp\*%7?g۰sy9yF hYj ۙrT𮓩hRi_b8cpiZ\U4JmEp_ u+ Kor'8LI1]aV7ڕER kQEQEQEQEQEQEQEQEQEUMVO+G?)V覝Տ#m  hVZTo ?ٮX>94 iW1bOy'yEt Tu9u 6un/ ?FrDeQ`~xk^ \v-kG"NZퟝLWQJ8:nאU쒷y^d)Ze1ijd`u?zYC/&wnF1ֽrj5ǚM᫏"lB֪$9YK=2 *ޑ"lb4J-V%)lXÌ޽Onkӄgc$KymhfkuRn3[KjIoXԱ?^WUE%^ܖ_ N%c˼]!-ge2X0EzMImnCDd{ EMJQV—$/U) %qm"HAg{_ĈUڊJ 5%r6]5a)4$UM9 ៥kMxWubh0?,~:~5TVZӎ3ZK[_|AYk%ڬA OL~|5YP1cBgz 3s)+n ?+'ʟٞmc ,\ӱ3@{ d+ːJёé=qz:)iE-WQf y`JE;!4c ~c[L?= $v$7>#^&Yk%X,O$U >stream x  Om783  endstream endobj 17 0 obj <>stream JFIF``C    $.' ",#(7),01444'9=82<.342C  2!!22222222222222222222222222222222222222222222222222" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( m{HV*ڝ 2֍sD$;k]-j** jmZކ6PϷXkW״y,H$c``qW_Wx4pYd]pI"TnϿD1Vn57N]KEgi70n63# :*Zޡyڬ4:Гp vFJ{m龖u_!Fxgnz犯6cjP <,08 - bE^Z7wmfON4%pJ<H%f\OnMowC۾ǽG6<_jx0&s7kvߙokVkY~nn䲺k[X0eXuV ~ILA+G#I(D8qc=>J'}77h/Uknmkkb 0yHw/6@2nY*pMzU3%ėڌʻe/9I>OS_zwqlTM$1!vzڥʺy22eg{/㱷EgX\?lJ8cU4I #|K3G|T{ƿZZunTpCp*H1S0I\։r,f ěsR>hJq:Z+ -kP[ '̀ 8B޻F9fB<8D>hݴ5NDn+E說uZk6(95Gyd , 9kVh驖cdex[O!U'}me}SZwТ5;hMΌR ϲp"5iOW|LS d {u*mMow4Z4baIXcnf>L«hIc}h4lHg'R*uٽ~ocVʳէ{~`HdS!r+3Cm{TWx24VgQccm{u"=ŰNy'&U Eٻ~-lNr֨WIѥ;W>z+YT3*RWi4׫8ȗĚ̐Zrо ~EO XOԒM]mllͭ[#l%IMIikV"v''EPG9@``n^s _vbWe[3ImjK}\iY >}Ac1GI]VkזׂMKsn!rK2@ێ=xku{MJ8EDR.v)_KIkz>M +mv_k2sRj#$d>Zl;5i!)70 :^v?Rnm{ZnkYWzXiqVj a idzI cK>n[}鹭Eb6q6wXy۰Mqjk Vy4Qotdtf߯QRSmZmB;iI $l3gVf]&k|QlaB$&pL#oN55&!b+rVvپz]ڽivI:@$Yv&F'>m͵ 3D[pe=OqIњWȨi\iQX"v:k"H)2Hb9$rN3[3(;HUY^љ] ʇ O|k%ՐVfrkzxшLn\]:Jq|JǶkRwooYRm,ѵӱYWz\bIYؑ'}(n^EEDzM"5u}f7/vkX$*8!YbEi" H򤌌3\'m9CqqJֲ: @KgɜL*A}gK$խS/+mEaEjw -ӬfY< ~5$!?ɫG 0xXemH=y*^KFW+]WA Xrڨktk@¼eeی;g5O]M絷ZD2m1|prQ}]DTӌ%%{{Ym(eB$18 d>i:v N2FGҥQ_r劥z/=4\ې&8Nx8Ts~V=Z X'g"YVwqw6q#$ӄ#%0U8KHi$7WSЩȧU ZhQRYv~RiS ((((m6d պᅾ[UM#zͽЬon>$78ǝ6#܎k G^5ZsUZzYjrik$XrIj[)R?}馕mm43|\ ێgH{ JqӗFk[]-4Iq)J,iAD['ciHF:VZ<Li>sBz'}֤pK{ ۩3B<EŜR*>H?J̩ay'rXP 's29cM.+j)CE*B VgY\fY.z e(FjW%# tΜYZs>߱IgԵkm."ٖ7qy$lgzun>%u?JjI&:LԖ:=: $qi =ңBm N[Wߦ~E=t>?Q7H,ඞh.4$䁏CYzT6O'$cuW3~V,ZSQ+͓&#.mjDL$hqQ (I_ZnSGMHᷓE2X\m3 vWF4 0[c,=֧mt- Yy5B TaIۖ6׽yEU Zb}?nTvpXbR]I䜚59.NJ0{rvZ5Oyu wmm<=XγfUıLoeDIp9'$ ~bvh`^Q\n3j:Ykd$h"0x侖ad̛Fߘ`Zzٻ<v,=:E: !a,,]ds9j4Vvc,=iJ[J[e_M\vAjϚ9%>- KwJܗGQ[JnLr2@ 7\ӊ^).P{sIavzƕi-vtأO k-od@_rpGo?Kb{#vDbz?[}&M37 i<$t9׭ZAIK=TZוOVe;l?ʹ^?*J`EKifXҪkOՉʭ2_7o+a})!7&t2U=>-[E5w<7QGcVz=iX:i t'ҫ/rY.+ 1ӌө7oLε |$m[׺h&$wX6+ $tVN{w 5HaҭW;嶇ly (((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((( endstream endobj 18 0 obj <>stream x  Om7^ Oa endstream endobj 19 0 obj <> endobj 20 0 obj <> endobj 25 0 obj <>stream x nH@paX endstream endobj 26 0 obj <>stream x nH@o endstream endobj 27 0 obj <> endobj 28 0 obj [250 0 0 0 0 0 0 0 0 0 0 564 0 333 250 0 500 500 500 500 500 0 500 500 500 500 0 0 0 0 0 0 921 0 0 0 722 611 556 722 722 0 0 0 0 889 0 0 556 0 667 556 0 0 0 0 0 0 611 0 0 0 0 0 0 444 500 444 500 444 0 0 500 278 0 500 278 778 500 500 500 0 333 389 278 500 500 722 500 500 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 333 ] endobj 22 0 obj <>stream JFIF``C    $.' ",#(7),01444'9=82<.342C  2!!22222222222222222222222222222222222222222222222222bb" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( *kZ= )՘W5mZx?sS)(rbzz.-+E_|dF>g?qZP ]3N'K:?ƸT/.\$s1c 'j9W᭏=Mrķsݓ@aGrZ}{R}NՋHf?^d!,.@#VnZ)BJPG i6ב9O?0H\kǝףG1>X;} ExM_@eZ}H2Bo_U a1Jr˺-aUL cZݫ L7YSG/k?oo\jSѫV]֙宙>bx.2)YWN/XޑxVRr{W\֡p~Z7gS憌#ˌ5JOkT{Y$9$5b'JAI a}%hT(((kH0zVBEY[RI(GJ?zӉ[?kFniE?D;o l_DP^Xž "Lh?g |{עW|mIW̗ɏL,WQCz-Wv\@He@єRWWTV.⤂( ( ( ( ( ( ( ( ( ( ( ( ( ziSs('*:e>#j\!eG9_Ɍ-/S#N_GxA'4?2+><(niv%Lp?aG2_Iѽ~kNe>XՂ (((((F`Y I=c9ũՍ0}E $=M ||?hjz#59½OC+oEQEQEQEQEQEQEQEQEQEQEQEQEW;65(jnm;<>/sW~ʯT4bXZJy UEYk (;QEIaEPEPYֳmX5,x0yvmwĶZDH[>X>Uծ{ƹ|EQPz^*ϚzG<\7.7y^V/ԯe}Hr}~SZs;p } J*:ӟ4lNHcfF q*<%s] o,z'eд ( ( ( ( ( ( ( ( ( ( ( ( ( +h[TělOSa )CV &8ş#im ҺkIT׆>+)lݶ~^ s_QJT~΢7ȩk>l]GȮϟekYx^=+Spߊ\5l5*F\u|+)[˧{%{|=?Z5o^݆1i~r?5Q]r4ڻUfԜ?t=*ߔ<3cVoĒkN_Wr>ʍ?g+P(((((((((((((߄a~*^Ù-e?އ?_5/e(H+ωOMUM^%t ;{cb3 cuV`k8 s\j=KtquV s^d|':d4sYP:մg:M訄y+E3Q@rLPw܁ޕ#Iifu˫梹k j%#a[a{vX5 <]/.Ѱ(vO},: q̧0cw>g`p IQ^QQ@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@g..-55\%ʯwG^ Yٵ;V's[ӭ}]U-5;Gr`:'KG9k!W]򥾣Z1_k|CJ}9[ϗo?לj^n4學W/#{l[%вEK]Ha*AsΖQ^ZNƿsҎq,: oY杦sZ/~u2IO~?.e_XsX?k*?2G}%pƹ&=K!..;QGonZ/ i4(|<կ'Ov/`OW (((((((((((((((<2"V`)\>|v08 Z( ( ( +7YcSFڇc65Mťvnɕ/4;P+_Nc,b=MNQى/ts)QПkRú.A,`aѣE?MD : nލPcϢ5-AAEPExK֧O`-a9?iKa9$osN(0(((((((((((z+qBԃTs\q [3kG|?wwXEu2դB)Mj὜6R~j6dTFLr@ bWW9]،EJxYۡÇNxxt8+z$oR>V>VNj|=i1}j$|$|t7WDx%y"E:9/ \ PI4A({U~ Z;u՛!/+s%K1 @A#k>X;CUB]TU88s-wrpq~j ;ƻnŧ H\4`N΀XzYTs)ՔtI)bH5K ,RFQ2l{&o~,fl;|Aj~)XeزE PsʁV<mw[iOl#dP ޠnNsZBp7i}pI$Js6qnD1ykZ<:ڹcԓ'T&*mNYQT18J^)jkoEe [xZfm,Y@Ԍ m:/Ŧ<.مP;zV?~6ݶy ޹U9B&TeOI껛V 4jTFN `Ӯr+GP%_VFBI( Z|%]Z-C;bn8 GB+v-A𦩨뗷r2z8JrSV۶2ԋ$~д}14Ni^#K! D, O@NzWH%Kkw* B2O%{w?ABӯ{i Ȇ(@3d凄\ݕLqz>-6y jp>?|aP>?9j? C|XehmQ (8C\F|µ 'kt♜k OkhS bSyp0Y[\!<yj3EqO $R(du9 Ba"։.co2g夑8?s׍ëw17Ṿ; Q\:}$_;{=SOGXUp\*%7?g۰sy9yF hYj ۙrT𮓩hRi_b8cpiZ\U4JmEp_ u+ Kor'8LI1]aV7ڕER kQEQEQEQEQEQEQEQEQEUMVO+G?)V覝Տ#m  hVZTo ?ٮX>94 iW1bOy'yEt Tu9u 6un/ ?FrDeQ`~xk^ \v-kG"NZퟝLWQJ8:nאU쒷y^d)Ze1ijd`u?zYC/&wnF1ֽrj5ǚM᫏"lB֪$9YK=2 *ޑ"lb4J-V%)lXÌ޽Onkӄgc$KymhfkuRn3[KjIoXԱ?^WUE%^ܖ_ N%c˼]!-ge2X0EzMImnCDd{ EMJQV—$/U) %qm"HAg{_ĈUڊJ 5%r6]5a)4$UM9 ៥kMxWubh0?,~:~5TVZӎ3ZK[_|AYk%ڬA OL~|5YP1cBgz 3s)+n ?+'ʟٞmc ,\ӱ3@{ d+ːJёé=qz:)iE-WQf y`JE;!4c ~c[L?= $v$7>#^&Yk%X,O$U >stream JFIF``C    $.' ",#(7),01444'9=82<.342C  2!!22222222222222222222222222222222222222222222222222" }!1AQa"q2#BR$3br %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz w!1AQaq"2B #3Rbr $4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz ?( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( m{HV*ڝ 2֍sD$;k]-j** jmZކ6PϷXkW״y,H$c``qW_Wx4pYd]pI"TnϿD1Vn57N]KEgi70n63# :*Zޡyڬ4:Гp vFJ{m龖u_!Fxgnz犯6cjP <,08 - bE^Z7wmfON4%pJ<H%f\OnMowC۾ǽG6<_jx0&s7kvߙokVkY~nn䲺k[X0eXuV ~ILA+G#I(D8qc=>J'}77h/Uknmkkb 0yHw/6@2nY*pMzU3%ėڌʻe/9I>OS_zwqlTM$1!vzڥʺy22eg{/㱷EgX\?lJ8cU4I #|K3G|T{ƿZZunTpCp*H1S0I\։r,f ěsR>hJq:Z+ -kP[ '̀ 8B޻F9fB<8D>hݴ5NDn+E說uZk6(95Gyd , 9kVh驖cdex[O!U'}me}SZwТ5;hMΌR ϲp"5iOW|LS d {u*mMow4Z4baIXcnf>L«hIc}h4lHg'R*uٽ~ocVʳէ{~`HdS!r+3Cm{TWx24VgQccm{u"=ŰNy'&U Eٻ~-lNr֨WIѥ;W>z+YT3*RWi4׫8ȗĚ̐Zrо ~EO XOԒM]mllͭ[#l%IMIikV"v''EPG9@``n^s _vbWe[3ImjK}\iY >}Ac1GI]VkזׂMKsn!rK2@ێ=xku{MJ8EDR.v)_KIkz>M +mv_k2sRj#$d>Zl;5i!)70 :^v?Rnm{ZnkYWzXiqVj a idzI cK>n[}鹭Eb6q6wXy۰Mqjk Vy4Qotdtf߯QRSmZmB;iI $l3gVf]&k|QlaB$&pL#oN55&!b+rVvپz]ڽivI:@$Yv&F'>m͵ 3D[pe=OqIњWȨi\iQX"v:k"H)2Hb9$rN3[3(;HUY^љ] ʇ O|k%ՐVfrkzxшLn\]:Jq|JǶkRwooYRm,ѵӱYWz\bIYؑ'}(n^EEDzM"5u}f7/vkX$*8!YbEi" H򤌌3\'m9CqqJֲ: @KgɜL*A}gK$խS/+mEaEjw -ӬfY< ~5$!?ɫG 0xXemH=y*^KFW+]WA Xrڨktk@¼eeی;g5O]M絷ZD2m1|prQ}]DTӌ%%{{Ym(eB$18 d>i:v N2FGҥQ_r劥z/=4\ې&8Nx8Ts~V=Z X'g"YVwqw6q#$ӄ#%0U8KHi$7WSЩȧU ZhQRYv~RiS ((((m6d պᅾ[UM#zͽЬon>$78ǝ6#܎k G^5ZsUZzYjrik$XrIj[)R?}馕mm43|\ ێgH{ JqӗFk[]-4Iq)J,iAD['ciHF:VZ<Li>sBz'}֤pK{ ۩3B<EŜR*>H?J̩ay'rXP 's29cM.+j)CE*B VgY\fY.z e(FjW%# tΜYZs>߱IgԵkm."ٖ7qy$lgzun>%u?JjI&:LԖ:=: $qi =ңBm N[Wߦ~E=t>?Q7H,ඞh.4$䁏CYzT6O'$cuW3~V,ZSQ+͓&#.mjDL$hqQ (I_ZnSGMHᷓE2X\m3 vWF4 0[c,=֧mt- Yy5B TaIۖ6׽yEU Zb}?nTvpXbR]I䜚59.NJ0{rvZ5Oyu wmm<=XγfUıLoeDIp9'$ ~bvh`^Q\n3j:Ykd$h"0x侖ad̛Fߘ`Zzٻ<v,=:E: !a,,]ds9j4Vvc,=iJ[J[e_M\vAjϚ9%>- KwJܗGQ[JnLr2@ 7\ӊ^).P{sIavzƕi-vtأO k-od@_rpGo?Kb{#vDbz?[}&M37 i<$t9׭ZAIK=TZוOVe;l?ʹ^?*J`EKifXҪkOՉʭ2_7o+a})!7&t2U=>-[E5w<7QGcVz=iX:i t'ҫ/rY.+ 1ӌө7oLε |$m[׺h&$wX6+ $tVN{w 5HaҭW;嶇ly (((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((( endstream endobj 24 0 obj <> endobj 29 0 obj <> endobj 30 0 obj [250 ] endobj 2 0 obj << /ProcSet [/PDF /Text /ImageB /ImageC /ImageI] /Font << /F1 3 0 R /F2 4 0 R /F3 5 0 R >> /XObject << /I0 13 0 R/TPL1 14 0 R/TPL2 21 0 R >> >> endobj 6 0 obj <> /H /I>> endobj 31 0 obj << /Title (Congresso ESC 2017- Ictus e fibrillazione atriale, anche nei pazienti a pi alto rischio LIXIANA altrettanto efficace e pi sicuro del warfarin ) /Author (Daiichi Sankyo) /Subject (Congresso ESC 2017- Ictus e fibrillazione atriale, anche nei pazienti a pi alto rischio LIXIANA altrettanto efficace e pi sicuro del warfarin ) /Creator (TCPDF) /Producer (TCPDF 6.2.13 \(http://www.tcpdf.org\)) /CreationDate (D:20181219063101+01'00') /ModDate (D:20181219063101+01'00') /Trapped /False >> endobj 32 0 obj << /Type /Metadata /Subtype /XML /Length 4545 >> stream application/pdf Congresso ESC 2017- Ictus e fibrillazione atriale, anche nei pazienti a più alto rischio LIXIANA® è altrettanto efficace e più sicuro del warfarin Daiichi Sankyo Congresso ESC 2017- Ictus e fibrillazione atriale, anche nei pazienti a più alto rischio LIXIANA® è altrettanto efficace e più sicuro del warfarin 2018-12-19T06:31:01+01:00 TCPDF 2018-12-19T06:31:01+01:00 2018-12-19T06:31:01+01:00 TCPDF 6.2.13 (http://www.tcpdf.org) uuid:bb35501a-8bf0-d672-678e-cf5052879c3a uuid:bb35501a-8bf0-d672-678e-cf5052879c3a http://ns.adobe.com/pdf/1.3/ pdf Adobe PDF Schema http://ns.adobe.com/xap/1.0/mm/ xmpMM XMP Media Management Schema internal UUID based identifier for specific incarnation of a document InstanceID URI http://www.aiim.org/pdfa/ns/id/ pdfaid PDF/A ID Schema internal Part of PDF/A standard part Integer internal Amendment of PDF/A standard amd Text internal Conformance level of PDF/A standard conformance Text endstream endobj 33 0 obj << /Type /Catalog /Version /1.5 /Pages 1 0 R /Names << >> /ViewerPreferences << /Direction /L2R >> /PageLayout /SinglePage /PageMode /UseNone /OpenAction [7 0 R /FitH null] /Metadata 32 0 R >> endobj xref 0 34 0000000000 65535 f 0000006915 00000 n 0000057451 00000 n 0000006987 00000 n 0000007093 00000 n 0000007204 00000 n 0000057610 00000 n 0000000015 00000 n 0000000465 00000 n 0000002156 00000 n 0000002607 00000 n 0000005155 00000 n 0000005625 00000 n 0000007318 00000 n 0000020647 00000 n 0000022395 00000 n 0000030894 00000 n 0000031374 00000 n 0000039043 00000 n 0000039349 00000 n 0000039535 00000 n 0000021865 00000 n 0000040822 00000 n 0000049321 00000 n 0000056990 00000 n 0000039591 00000 n 0000039902 00000 n 0000040154 00000 n 0000040406 00000 n 0000057175 00000 n 0000057427 00000 n 0000057882 00000 n 0000058761 00000 n 0000063389 00000 n trailer << /Size 34 /Root 33 0 R /Info 31 0 R /ID [ ] >> startxref 63598 %%EOF

Congresso ESC 2017- Ictus e fibrillazione atriale, anche nei pazienti a più alto rischio LIXIANA® è altrettanto efficace e più sicuro del warfarin

Barcellona, 29 agosto 2017 - LIXIANA® (edoxaban) è altrettanto efficace e più sicuro del warfarin per tutti i pazienti affetti da fibrillazione atriale non valvolare, anche quelli a più alto rischio di ictus o eventi embolici sistemici (secondo la scala CHADS2DS2-VASc). A dimostrarlo è l'ultima sotto-analisi del trial clinico ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor XA next GEneration in Atrial Fibrillation), presentata da Daiichi Sankyo al Congresso Europeo di Cardiologia che sta per concludersi a Barcellona.

I risultati generali dello studio ENGAGE AF-TIMI 48 avevano già dimostrato che, nei pazienti con FANV, edoxaban in monosomministrazione giornaliera fosse altrettanto efficace del warfarin per la prevenzione di ictus o di eventi embolici sistemici, e che al contempo riducesse significativamente il rischio di sanguinamenti. Questa nuova sotto analisi ha confermato che il vantaggio di edoxaban rispetto al warfarin si mantiene indipendentemente dai valori del CHA2DS2VASc, che valuta il rischio di ictus in modo più accurato rispetto al precedente CHADs.

Oltre ad approfondire il profilo rischio-beneficio di edoxaban nella prevenzione dell'ictus, questa sotto analisi dimostra che edoxaban, all'aumentare del rischio tromboembolico, garantisce una riduzione assoluta dei sanguinamenti (inclusi i sanguinamenti maggiori, emorragie intracraniche e ospedalizzazioni per patologie cardiovascolari) ancora maggiore rispetto ai pazienti trattati con warfarin; i risultati di sicurezza rimangono infatti invariati anche in pazienti con un punteggio più alto di CHA2DS2VASc (p-int=0,99 per sanguinamenti maggiori).

"Ridurre il rischio di ictus è di vitale importanza per una gestione efficace della fibrillazione atriale non valvolare. I dati di edoxaban in pazienti a diversi livelli di rischio possono aiutare molto gli specialisti nella pratica clinica, consentendo loro di prendere la decisione migliore per i singoli pazienti", ha spiegato il cardiologo Joris De Groot, ricercatore dell'Università di Amsterdam e principale autore dello studio.

Edoxaban dunque protegge efficacemente anche i pazienti a più alto rischio di ictus o eventi embolici sistemici. La sua efficacia rispetto al warfarin per la prevenzione dell'ictus rimane stabile in pazienti con diversi CHA2DS2VASc (p-int=0,546 per ictus ed eventi embolici sistemici).

"Questa nuova sottoanalisi è solo una delle tante dimostrazioni dell'impegno di Daiichi Sankyo nello sviluppo delle ricerche scientifiche in ambito cardiovascolare, con l'obiettivo di migliorare la cura e la qualità di vita dei pazienti, con particolare attenzione ai soggetti più vulnerabili a più alto rischio", ha dichiarato il dottor Wolfgang Zierhut, direttore esecutivo del Cardiovascular Medical Affairs di Daiichi Sankyo.

Le analisi dell'ENGAGE AF-TIMI 48 confermano e supportano le Linee Guida ESC 2016 per la gestione della FA, che raccomandano l'utilizzo degli anticoagulanti orali diretti come ampiamente preferibili agli antagonisti della vitamina K, quale il warfarin, per la prevenzione dell'ictus nei pazienti con FANV, proprio grazie alla riduzione del rischio di sanguinamenti che questo tipo di trattamento comporta.

ENGAGE AF-TIMI 48 è un trial clinico globale di fase 3 che ha randomizzato 21.105 pazienti affetti da fibrillazione atriale non valvolare in tre bracci di trattamento: warfarin, edoxaban alta dose (60 o 30 mg una volta al giorno), edoxaban bassa dose (30 o 15 mg una volta al giorno). In questa particolare sotto-analisi, i pazienti sono stati raggruppati secondo il loro CHA2DS2VASc (≤2, 3, 4, 5, ≥6) e si sono valutate efficacia (ictus ed eventi embolici sistemici) e sicurezza (sanguinamenti maggiori, emorragie intracraniche e risultati di ospedalizzazioni cardiovascolari) di edoxaban alta dose rispetto al warfarin.