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????RE-LY ??
44??? 951???
R

• ??????????
• ????2?(1-3?)
• ??????????

5
????RE-LY ??
NEJM. 2009 1139
6
RECOVER??

• ???????(DVT)??
• 29???,228???,2539?

????
????9?
???? 150mg po bid
???? INR 2-3
????6???VET????????? ???????????????????????
RE-COVER Study Group, NEJM 2009
7
RECOVER??????????????????
RE-COVER Study Group, NEJM 2009
8
2010??????????

• ???? EINSTEIN DVT III?????????
• ???? ROCKET AF??????
• ???? Averroes III?????????
• ????APPRAISE-2 III?????????????????

9
????EINSTEIN DVT III???????DVT???
?????????DVT(??PE),????????????????????????/VKA
2010 ESC
10
???????????MWH/VKAs????
???? (n1731) ???? (n1731) ????/VKA (n1718) ????/VKA (n1718) HR 95CI HR 95CI
n () n ()
VTE????() 36 (2.1) 51 (3.0) 0.68 (0.44-1.04)
Plt0.0001
11
????????????LMWH/VKAs?????????
???? (n1718) ???? (n1718) ????/VKA (n1711) ????/VKA (n1711) HR 95CI P? HR 95CI P?
n () n ()
?????????????() 139 (8.1) 138 (8.1) 0.97 0.76-1.22 P0.77
?????() 14 (0.8) 20 (1.2)
2010 ESC
12
????????????LMWH/VKAs?????????
???? () ????/VKA () HR (95CI)
???? () ????/VKA () HR (95CI)
??????????????() 2.9 4.2 0.67 (0.47-0.95)
????() 2.2 2.9 0.67 (0.44-1.02)
?????() 0.7 0.8 0.79 (0.36-1.71)
????????,???????? ????????,???????? ????????,???????? ????????,????????
2010 ESC
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ROCKET-AF????
??(CHADS2??2?)
Rivaroxaban
???
??/?? /??? (n 14,000)
INR ???2.5 (2.0-3.0)
20 mg/d 15 mg/Cr Cl 30-49 ml/min
????,??????
???????????
AHA 2010
14
????
???? (N7081) ??? (N7090)
CHADS2 ?? 2 () 3 () 4 () 5 () 6 () 3.48 13 43 29 13 2 3.46 13 44 28 12 2
VKA??? () 62 63
????? () 63 62
??? () 90 91
??? () 40 39
??/TIA/???() 55 55
MI?() 17 18
AHA 2010
15
??????????????????
???? ???
????? 1.71 2.16
???
????
?????()
HR (95 CI) 0.79 (0.66, 0.96) P(???) lt0.001
?
No. at risk ???? 6958 6211 5786
5468 4406 3407 2472 1496
634 ??? 7004 6327 5911
5542 4461 3478 2539 1538 655
AHA 2010
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?????? ????????????
  ???? ???    
Event Rate Event Rate HR(95 CI) P
On Treatment N 14,143 1.70 2.15 0.79 (0.65,0.95) 0.015
ITT N 14,171 2.12 2.42 0.88 (0.74,1.03) 0.117
?????
????
ITTintention to treat
AHA 2010
17
????????
???? ???
????? ????? HR (95 CI) P-value
CV??,??,?? 3.11 3.63 0.86 (0.74, 0.99) 0.034
?????? ?????? 0.261.340.06 0.441.420.10 0.59 (0.37, 0.93)0.94 (0.75, 1.17)0.65 (0.25, 1.67) 0.0240.5810.366
?CNS?? 0.04 0.19 0.23 (0.09, 0.61) 0.003
MI 0.91 1.12 0.81 (0.63, 1.06) 0.121
????? ???? ????? ???? 1.871.530.190.15 2.211.710.300.20 0.85 (0.70, 1.02)0.89 (0.73, 1.10)0.63 (0.36, 1.08)0.75 (0.40, 1.41) 0.0730.2890.0940.370
?????????? ?????100???
18
????????
???? ???
????? ????? HR (95 CI) P-value
?????, ??,?? 4.51 4.81 0.94 (0.84, 1.05) 0.265
???? ?? ?? ???? 0.26 1.62 0.15 0.44 1.64 0.14 0.58 (0.38, 0.89) 0.99 (0.82, 1.20 1.05 (0.55, 2.01) 0.012 0.916 0.871
?CNS?? 0.16 0.21 0.74 (0.42, 1.32 0.308
MI 1.02 1.11 0.91 (0.72, 1.16) 0.464
????? ???? ????? ???? 4.52 2.91 1.15 0.46 4.91 3.11 1.22 0.57 0.92 (0.82, 1.03) 0.94 (0.81, 1.08) 0.94 (0.75, 1.18) 0.80 (0.57, 1.12) 0.152 0.350 0.611 0.195
??????????? ?????100???
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ROCKET-AF ??

• ??
• ????????????CNS????????
• ???????AF,???????????
• ?????????,??????????
• ???
• ??????????????
• ??????????????????????
• ??
• ???????,??????????????

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????AVERROES trial

• ?????????????????AF??

?????
???? 5mg po bid
???? 81-324mg qd
??????Apixaban???????????????????? ?????????????
?????????????/36? ????5600?????2007?9?????201
0?8? ??????????????,?????? ??????2010?8?30??ESC???
??
http//clinicaltrials.gov/ct2/show/NCT00496769 201
0 ESC
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AVERROES trial ????????????????????
2010 ESC
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APPRAISE-2????????ACS????

• ???? ??, MI, ????????????
• ????7500????,??????????????????,???????
• ???????????????

Bristol-Myers Squibb and Pfizer. 20101-11-19
23
???? ARISTOTLE trial

• ?????????AF??

Apixaban 5mg po bid
??? ??INR2-3

• ???????????????????????
• ???????????????
• ????18183?
• ????2006?12?????2011?4?

http//clinicaltrials.gov/ct2/show/NCT00412984
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? ?
25
????????????
???????1(PAR-1)???
SCH-530348 E5555
ADP P2Y12?????
TXA2?????
???? ???? ???? ????
S18886
Am Heart J.2010160595
26
??????ADP P2Y12???????????
???? ???? ???? ????
??
??????
P0.008
P0.003
?????
Plt0.001
JACC.2010561542-1551
27
?????????????ACS??PCI??????????
TRITON-TIMI 38??
?PCI?ACS???13,000?
15??
??????
HR0.81 Plt0.001
????
12.1
10
9.9
???
????
5
()
??????
HR1.32 P0.03
????
2.4
1.8
????
0
(?)
450
0
60
120
180
240
300
360
390
420
330
270
210
150
90
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?????????????????????? ?????????TIMI???
N Engl J Med 20073572001-2015
28
????????????
TRITON-TIMI 38??
15???TIMI????
NNH167
2.4
1.8
(N6716)
???()
1.4
(N6741)
1.1
0.9
0.9
0.4
0.3
0.3
0.1
TIMI ??? ???? ???? ??? ????
HR 0.32 1.52 1.25 4.19 1.12
P 0.03 0.01 0.23 0.002 0.74
N Engl J Med 20073572001-2015
29
?????????????????????
PLATO??
?????????,????,????
????
11.7
????
9.8
?????()
HR0.84(95CL0.77-0.92)Plt0.001
??????
???????
???? 9291 8521 8362 8124 6650 5096 4047
???? 9333 8628 8460 8219 6743 5161 4147
N Engl J Med. 20093611045-1057
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???????????????
PLATO??
P?NS
???()/?
PLATO ??? TIMI ??? ????? PLATO ?? ??/????? ?????
N Engl J Med. 20093611045-1057
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??????????????
32
2010ESC?????????????????????ACS

• ?ST???????
• ????I,C
• ????I,C
• ????IIa,B
• ????I,B
• ST???????
• ????I,B
• ????I,C
• ????I,B
• ????I,B

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8?????,?25570???,674?????
Lancet.Published Online December 7, 2010
35
???????????20?????20
3???,????vs.?????????20????????
25
20
?? 20
HR 0.80, 95CL 0.72-0.88, plt0.001
15
10
5
0
0
5
10
15
20
?????
Lancet.Published Online December 7, 2010
36
?????? ??????????
????????(75-1200 mg)vs???

• ??BDAT?TPT?SALT ?UK-TIA????14 033???,????6?,????18
  .3?

Lancet.2010 376(9754)1741
37
??????????????
???????(75-300 mg)vs???
??? ??? ??? ??? ??? ???
n/N HR P n/N HR P
???? 196/8073 0.75 0.02 130/8073 0.61 0.005
????2.5? 185/7383 0.69 0.003 119/7383 0.54 0.001
????5? 135/5077 0.62 0.003 91/5077 0.48 0.001

• ??TPT, SALT , UK-TIA(????300mg?)???????????2.5??
  5????

Lancet.2010 376(9754)1741
38

• Professor Peter Rothwell, John Radcliffe
  Hospital, Oxford, and University of Oxford, UK,
  noted that previous guidelines have rightly
  cautioned that in healthy middle aged people the
  small risk of bleeding on aspirin partly offsets
  the benefit from prevention of strokes and heart
  attacks, but the reductions in deaths due to
  several common cancers will now alter this
  balance for many people.

????????Peter Rothwell???????????????,???????????
??,???????????????????????????,???????????????????
??????,????????,?????
Lancet.Published Online December 7, 2010
39
????????

• ????????,??Wisconsin???Karl Link????????(??)??????
  ???,????????????????
• ???????????-???,?????????
• ????????90

NEJM 20033491762
40
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?????????????

• ???????????????????????
• ACCP8th??????????????????

Anderson, Circulation.20072563
43
?????? CHADS 2 ??
???? ??

• ????? CHF
• ????? HP
• 75? AGE
• ??? DM
• ???TIA Stroke

1 1 1 1 2
Gage et al. JAMA, 2001, 285 28642870
JAMA. 2001 2864
44
CHADS 2 ??????
???---1????()
??---1?????()
CHADS 2 ??
Gage. JAMA 2001 2864
Hylek. Circulation 20072689
45
2006?ACC/AHA/ESC????
????? ASA 81- 325mg
1?????ASA 81- 325mg ? ??? 1????gt1????? ???
???? ????TIA???,?????,??? ????
75?????????LVEF35???? ???? ???6574?????
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2010?ESC????CHA2DS2VASC??
????AF???????????? ????AF????????????
??????(2?) ???????(1?)
??/TIA/????? ??75? HF /???LV????(EF0.4) ??? ??? ?? ?? 65-74? ????
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CHA2DS2VASC??
???? ??
CHF/LV????(C) 1
???(H) 1
??75?(A) 2
???(D) 1
??/TIA/???(S) 2
????(V) 1
??65-74(A) 1
??(??)(Sc) 1
??? 9
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2010ESC??????????
???? CHADS2-VASc ?? ????
1????????2???????? 2 OAC
1???????? 1 OAC ??????75-325mg??OAC
????? 0 ????75-325mg/d??????? ????
OAC ?????
49
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