1 update on antiplatelet and anticoagulant drugs: sticky stuff kfj ng may 2011
TRANSCRIPT
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Anti-Xa and thrombus formation?
Xa
Extrinsic Pathway
IntrinsicPathway
VIII
V
IIa THROMBUS
AT
5aXa activity of AT-penta complex blocks initial thrombin generation & thrombin recruitment through feedback loops
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Fondaparinux (N=1098) LMWH (N=1107)Matisse DVTFatal PE 5 (0.5 %) 5 (0.5 %)
Non-fatal PE or DVT 38 (3.5 %) 40 (3.6 %)
Total symptomatic recurrent VTE 43 (3.9 %) 45 (4.1 %)
-0.15 %
= 3.5%0 1.5% -1.8%
Fondaparinux - LMWH (95 % CI )
Primary Efficacy Outcome (non-fatal or fatal recurrent VTE to 3 months)
Fondaparinux (N=1103) UFH (N=1110)
Fondaparinux - UFH (95 % CI )
Matisse PE
-1.2%
= 3.5%0 0.5% -3.0%
Fatal PE 16 (1.5 %) 15 (1.4 %)
Non-fatal PE or DVT 26 (2.4 %) 41 (3.6 %)
Total symptomatic recurrent VTE 42 (3.8 %) 56 (5.0 %)
ATI S S
EM ... .
. ..
NEJM 2003;349:1695
Ann Intern Med 2004;140:867
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Matisse DVTFondaparinux
sc LMWH 1.2%
1.1%
3.0%
2.6%
0% 2% 4% 6% 8%
Major bleed Clinically relevant non-major bleed
1.1%
1.3%
5.2%
3.2%
0% 2% 4% 6% 8%
3.7 %
4.2 %
Principal Safety OutcomeMajor bleeding during initial
treatment
Fondaparinux
iv UFH
Matisse PE
ATI S S
EM ... .
. ..
4.5 %
6.3 %NEJM 2003;349:1695
Ann Intern Med 2004;140:867
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Copyright ©2010 American Heart Association
Mackman, N. et al. Arterioscler Thromb Vasc Biol 2010;30:369-371
Targets of new anticoagulant drugs
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Gp IIb/IIIa (integrin αIIbβ3) antagonists
• Abciximab (Reopro)
• Eptifibatide (Integrilin)
• Tirofiban (Aggrastat)
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Gp IIb/IIIa antagonists FDA approval
• PCI– Abciximab– Eptifibatide
• ACS– Eptifibatide– Tirofiban
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P2Y12 inhibitors
• Irreversible– Clopidogrel (Plavix)– Prasugrel (Effient)
• Reversible– Ticagrelor (Brilinta)– Cangrelor
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Figure 1 The CHAMPION trials reaffirm that pretreatment with a P2Y12 antagonist is superior to delaying treatment until after the PCI procedure
David P. Faxon (2010) Cangrelor for ACS—lessons from the CHAMPION trialsNat. Rev. Cardiol. doi:10.1038/nrcardio.2009.247
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Monitoring
• Coagulation– TEG– PT/aPTT
• Platelet– PFA-100– Thrombelastography (TEG) Platelet Mapping– VerifyNow