-
7/29/2019 ( Xarelto) : .
1/20
( Xarelto)
: .
.
..
19.02.2013
05.03.2013
http://athero.ru/boss.htmhttp://athero.ru/boss.htm
-
7/29/2019 ( Xarelto) : .
2/20
ATLAS TIMI-51
, . 1-7
983
: , ,
2.5 /2
5 /2
2.5 /2
5 /2
Mega
JLhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdf
1
1:
2: + 2
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdf
-
7/29/2019 ( Xarelto) : .
3/20
ATLAS-TIMI51
1 2
1053 14473
-3 -181
1050 14292
(N=15526)
,
(N=15342)
Gibson
CMhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdf
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305922.pdf
-
7/29/2019 ( Xarelto) : .
4/20
ATLAS-TIMI-51:
-,
,
0.84(95%CI
0.74-0.96)p=0.008
-
Mega JL et al for the ATLAS ACS 2TIMI 51 Investigators. NEJM
2012; 366: 9-19;
-
7/29/2019 ( Xarelto) : .
5/20
ATLAS-TIMI-51:
,%
-
Mega JL et al for the ATLAS ACS 2TIMI 51 Investigators. NEJM
2012; 366: 9-19;
2.5/2 5/2
0.84 (95%CI 0.72-0.97)p=0.02
5/2
0.85 (95%CI 0.73-0.98)p=0.03
0.66 (95%CI 0.51-0.86)p=0.02
0.94 (95%CI 0.75-1.20)p=0.63
2.5/2
,%
-
-
-
7/29/2019 ( Xarelto) : .
6/20
Kaplan-Meier .
95% .
(n=5113)
2.5/2(n=5114)
5 /2(n=5115)
(n=10229)
- ,, -
1 0.84(0.720.97)
0.85(0.730.98)
0.84(0.740.96)
- 1 0.66(0.510.86)
0.94(0.751.20)
0.80(0.650.99)
1 0.90(0.751.09
0.79(0.650.97)
0.85(0.721.00)
1 1.13(0.741.73)
1.34(0.902.02)
1.24(0.861.78)
1 0.89(0.551.45)
1.05(0.651.68)
0.97(0.641.47)
,, -
1 0.83(0.720.97)
0.84(0.730.98)
0.84(0.740.95)
1 0.68(0.530.87)
0.95(0.761.19)
0.81(0.661.00)
1 0.65(0.450.94)
0.73(0.511.04)
0.69(0.510.93)
Mega JL et al for the ATLAS ACS 2TIMI 51 Investigators. NEJM
2012; 366: 9-19.
-
7/29/2019 ( Xarelto) : .
7/20
Kaplan-Meier .
95% .
(n=5113)
2.5/2(n=5114)
5 /2(n=5115)
(n=10229)
TIMI,
1
3.46(2.085.77)
4.47(2.717.36)
3.96(2.466.38)
TIMI 1 1.62(0.922.82)
2.52(1.504.24)
2.07(1.273.37)
TIMI,
1
1.79(1.552.07)
2.39(2.082.75)
2.09(1.832.38)
12.83
(1.027.86)
3.74(1.3910.07)
3.28(1.288.42)
1 0.67(0.241.89)
1.72(0.753.92)
1.19(0.542.59)
Mega JL et al for the ATLAS ACS 2TIMI 51 Investigators. NEJM
2012; 366: 9-19.
-
7/29/2019 ( Xarelto) : .
8/20
ATLAS
Marciniak T.A. , Food & Drug Administration ( ATLAS-2), May
23, 2012
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs
/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305921.pdf
-
7/29/2019 ( Xarelto) : .
9/20
NDA 202-439 Rivaroxaban for Acute Coronary Syndromes
Thomas A. Marciniak, M.D.Food & Drug Administration, May 23,
2012
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs
/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305921.pdf
ATLAS Challenge:
ATLAS: ()
&
Missing Data & Questionable Quality
-
7/29/2019 ( Xarelto) : .
10/20
ATLAS
()
(incomplete follow-up)
/
TIMI
100 /
Marciniak T.A. , Food & Drug Administration, May 23,
2012
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs
/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305921.pdf
-
7/29/2019 ( Xarelto) : .
11/20
ATLAS-2
. () - , 2.5 .
( )
.the trial did not enroll enough patients at high risk of
bleeding, such as the elderly, and that therewere some seemingly
odd resultssuch as the fact that stroke was not reduced by
rivaroxaban, norwas there a reduction in MI with the 2.5-mg dose.
Added to this, the bleeding hazard withrivaroxaban in ATLAS-ACS 2
TIMI 51 was "unprecedented," one expert observed
,
.. 12% .
1 1.5%
. 1294
, 183,
177the trial results are not interpretable because about 12% of
the patients had incomplete follow-up, far higher than the
1% to 1.5% differences in the end-point rates between
rivaroxaban and placebo. A total of 1294 subjects discontinuedthe
trial prematurely, and the company was only able to contact 183, of
which 177 were confirmed to be alive.
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305921.pdf
-
7/29/2019 ( Xarelto) : .
12/20
ATLAS
T.A.Marciniak - FDA
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM305921.pdf
ATLAS
ATLAS , .
-
7/29/2019 ( Xarelto) : .
13/20
The committee members that voted no felt that they could not
rely on the evidence presented
at the meeting. There was concern about the bleeding risk and
the need to balance cardio-
vascular death versus life threatening bleeds. There were also
concerns about missing data.
, , , ,
( , ) .
. .
Summary Minutes of the Cardiovascular and Renal Drugs Advisory
Committee. May 23,
2012.http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/
Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM310093.pdf
,
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM310093.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM310093.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM310093.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM310093.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM310093.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM310093.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM310093.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM310093.pdf
-
7/29/2019 ( Xarelto) : .
14/20
ATLAS
( ) ( 2),
,
/ .
-
7/29/2019 ( Xarelto) : .
15/20
4 2013 . ,
ATLAS, , FDA
- ATLAS -
(vital status) 843 63% 1,338 , *
(, ,
?). TIMI,
, ? ,
, ATLAS , *.
theheart.org, FDA
- . second complete
response letter FDA ( FDA) Janssen
** ( FDA ).
*Wood S. FDA, again, seeks more info on rivaroxaban in ACS.
www.theheart.org. Mar 4, 2013.
**FDA Issues Complete Response Letter for XARELTO (rivaroxaban)
for the Reduction of
Cardiovascular Events in Patients with Acute Coronary
Syndrome.
http://www.prnewswire.com/news-releases/... Mar 4, 2013
http://www.theheart.org/http://www.prnewswire.com/news-releases/http://www.prnewswire.com/news-releases/http://www.prnewswire.com/news-releases/http://www.prnewswire.com/news-releases/http://www.prnewswire.com/news-releases/http://www.prnewswire.com/news-releases/http://www.theheart.org/
-
7/29/2019 ( Xarelto) : .
16/20
A.Komcsi .
Komcsi A., Vorobcsuk A., Kehl D., Aradi D.Use of new-generation
oral anticoagulant agents in patients receiving
antiplatelet therapy after an acute coronary syndrome.
, .
Arch Intern Med2012; DOI:10.1001/archinternmed.2012.4026.
-
7/29/2019 ( Xarelto) : .
17/20
,
. . .
263 48
*
, 95%
TIMI
*
P
-
7/29/2019 ( Xarelto) : .
18/20
() :
Komcsi A., Vorobcsuk A., Kehl D., Aradi D. Use of new-generation
oral anticoagulant agents in patients receivingantiplatelet therapy
after an acute coronary syndrome. Arch Intern Med2012;
DOI:10.1001/archinternmed.2012.4026.
-
7/29/2019 ( Xarelto) : .
19/20
Komcsi A. .: , -
() ,
().
>31000 ,
.
5 - , ,
2 - 3- (APPRAISE-2 ATLAS-ACS 2 TIMI 51).
( 3.03; 95% 2.20-4.16; < 0.001).
- 0.98; 95% , 0.90-1.06; =0.57.
Komcsi A., Vorobcsuk A., Kehl D., Aradi D. Use of new-generation
oral anticoagulant agentsin patients receiving antiplatelet therapy
after an acute coronary syndrome.
Arch Intern Med 2012;
DOI:10.1001/archinternmed.2012.4026.Hernandez AV. Arch Intern
Med 2012; doi:10.1001/2013.jamainternmed.293.
/
-
7/29/2019 ( Xarelto) : .
20/20
Hernandez A.V. No place for novel oral anticoagulantsin current
treatment of acute coronary syndromes.
Komcsi A. .
,
,
( 3.03; 95% 2.20-4.16; < 0.001).
- 0.98; 95% , 0.90-1.06;=0.57.
Komcsi A., Vorobcsuk A., Kehl D., Aradi D. Use of new-generation
oral anticoagulant agents in patients receivingantiplatelet therapy
after an acute coronary syndrome. Arch Intern Med 2012;
DOI:10.1001/archinternmed.2012.4026
Hernandez AV. Arch Intern Med 2012;
doi:10.1001/2013.jamainternmed.293.
