Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly...
-
Upload
amy-carter -
Category
Documents
-
view
222 -
download
0
Transcript of Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly...
![Page 1: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/1.jpg)
![Page 2: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/2.jpg)
![Page 3: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/3.jpg)
Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic protection, and improves net clinical
outcome.
Bivalirudin Advantage
![Page 4: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/4.jpg)
ATIIa
Hep
UFH
IIaS
C
Direct antithrombin
LMWH
AT Xa AT Xa
Pentasaccharide
![Page 5: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/5.jpg)
IIa II
Fibrinogen Fibrin clot
Extrinsic pathway
Intrinsicpathway
AT XaAT AT
Fondaparinux
Xa
Antithrombin
Fondaparinux: A Synthetic Factor Xa Inhibitor
Adapted with permission from Turpie AGG et al. N Engl J Med. 2001;344:619.
THROMBIN
![Page 6: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/6.jpg)
Key Steps in Coagulation Pathway
Inhibition of one molecule of factor Xa can inhibit the
generation of 50 molecules of thrombin2
Intrinsic pathway Extrinsic pathway
1 .Rosenberg RD, Aird WC. N Engl J Med 1999;340(20):1555–64.2 .Wessler S, Yin ET. Thrombo Diath Haemorrh 1974;32(1):71–8.
Intrinsic pathway
1
50
Xa X
II
FibrinFibrinogen
Clot
Xa
Va
PL
Ca2+
IIa
VIIIa
Ca2+
PL
IXa
![Page 7: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/7.jpg)
Herbert JM et al. Cardiovasc Drug Rev. 1997;15:1 .van Boeckel CAA et al. Angew Chem, Int Ed Engl. 1993;32:1671 .
·Once daily administration ·Rapid onset (Cmax/2=25 min)·Half life: 15-18 h.·Effects reversible with administration
of activated Factor VII (Novoseven®)·No liver metabolism·Renal clearance·No protein binding (other than AT)·No reported cases of HIT·No dose adjustment necessary in
elderly
Fondaparinux: A Synthetic Inhibitor of Factor Xa
![Page 8: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/8.jpg)
12,000 Patients with STEMI < 12 h of symptom onset:Inclusion ST mm prec leads or 2 mm limb leads 1
:ExclusionContra-ind. for anticoagulant, INR>1.8, pregnancy, ICH<12 mo .
12,000 Patients with STEMI < 12 h of symptom onsetInclusion: ST 2 mm prec leads or 1 mm limb leads
Exclusion: Contra-ind. for anticoagulant, INR>1.8, pregnancy, ICH<12 mo.
UFH not indicatedUFH not indicated
OASIS-6: Randomized, Double Blind
Lytics (SK, TPA, TNK, RPA), Primary PCI or no reperfusion (eg. late)Lytics (SK, TPA, TNK, RPA), Primary PCI or no reperfusion (eg. late)
StratificationStratification
UFH indicatedUFH indicatedRandomization Randomization
Fondaparinux2.5 mg Placebo
Fondaparinux2.5 mg UFH
JAMA 2006;295:1519-30
![Page 9: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/9.jpg)
Primary Efficacy OutcomeDeath/MI at 30 Days
Days
Cum
ulati
ve H
azar
d0.
00.
020.
040.
060.
080.
100.
12
0 3 6 9 12 15 18 21 24 27 30
UFH/Placebo
Fondaparinux
HR 0.86 95% CI 0.77-0.96
P=0.008
The OASIS-6 Trial Group. JAMA 2006;295:1519-30
![Page 10: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/10.jpg)
Death or MI 3 or 6 months
Days
Cum
ulati
ve H
azar
d
0.0
0.02
0.04
0.06
0.08
0.10
0.12
0 18 36 54 72 90 108 126 144 162 180
UFH/Placebo
Fondaparinux
HR 0.88 95% CI 0.79-0.99
P=0.029
The OASIS-6 Trial Group. JAMA 2006;295:1519-30
![Page 11: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/11.jpg)
•Primary :Efficacy:Death, MI, refractory ischemia day 9
Safety:Major bleeds
Risk benefit:Death, MI, refractory ischemia, major bleeds •SecondaryAbove & each component (especially deaths) at 30 & 180 d :•HypothesisFirst test non-inferiority, then test superiority :
•Primary: Efficacy: Death, MI, refractory ischemia 9 day
Safety: Major bleeds
Risk benefit: Death, MI, refractory ischemia, major bleeds•Secondary: Above & each component (especially deaths) at 30 & 180 d•Hypothesis: First test non-inferiority, then test superiority
![Page 12: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/12.jpg)
Death at 6 Months
Days
Cum
ulati
ve H
azar
d0.
00.
020.
040.
06
0 20 40 60 80 100 120 140 160 180
HR 0.8995% CI 0.79-0.99
p=0.037
Enoxaparin
Fondaparinux
![Page 13: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/13.jpg)
Death or MI: 6 Months
Days
Cum
ulati
ve H
azar
d
0.0
0.02
0.04
0.06
0.08
0.10
0.12
0 20 40 60 80 100 120 140 160 180
HR 0.9195% CI 0.84-0.99
p=0.036
Enoxaparin
Fondaparinux
![Page 14: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/14.jpg)
Major Bleeding: 6 Months
Days
Cum
ulati
ve H
azar
d
0.0
0.01
0.02
0.03
0.04
0.05
0.06
0 20 40 60 80 100 120 140 160 180
HR 0.7295% CI 0.63-0.82
p<<0.00001
Enoxaparin
Fondaparinux
![Page 15: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/15.jpg)
Death, MI, RI or Major Bleeding at 6 Months
Days
Cum
ulati
ve H
azar
d0.
00.
050.
100.
15
0 20 40 60 80 100 120 140 160 180
Enoxaparin
Fondaparinux
HR 0.8795% CI 0.81-0.93
p<<0.00001
![Page 16: Compared to Heparin/Enoxaparin with GP IIb/IIa inhibitors,Bivalirudin monotherapy significantly reduces major bleeding while providing similar ischemic.](https://reader034.fdocuments.net/reader034/viewer/2022051620/56649efd5503460f94c1189d/html5/thumbnails/16.jpg)
Fondaparinux
•Difficult to monitor (no aPTT or ACT)
•Long half-life•Catheter thrombosis
during PCI
DisadvantagesAdvantages•SC administration
―Potential exists for outpatient
management•Once-daily
administration•Predictable
anticoagulant response•Fixed dose•No antigenicity•Potentially no need for
serologic parameters•Does not cross the
placenta•HIT antibodies do not
cross-react•Decreased bleeding
complications vs UFH or LMWH
Simoons ML, et al. J Am Coll Cardiol. 2004;43:2183-2190.Yusuf S, et al. N Engl J Med. 2066;354:1464-1476 .