2004-10-25 13:24:03暈炫
antiplatelet therapy in NSTE ACS
Antiplatelet therapy in NSTE ACS
JAMA. Oct, 2004. Review
high risk in ACS
--elevated cardiac enzymes
==TnI > 0.05 ng/mL, CKMB > 3% of CK, CKMB > 16 mg/dL
--multiple episodes of chest pain
--current aspirin use
--previous revasculization
TIMI risk score: (TIMI = Thrombolysis in MI)
1. Age 65 years
2. Presence of at least three risk factors for CHD
risk factor方面
3. Prior coronary stenosis of 50 percent
4. Use of aspirin in prior seven days
history方面
5. Presence of ST segment deviation on admission ECG
6. At least two anginal episodes in prior 24 hours
7. Elevated serum cardiac biomarkers
admission後表現
poor prognositic factor
--ST elevation in aVR lead, in NSTEMI
Pathophysiology in ACS
--plaque rupture or erosion + subsequent thrombosis
--endothelial dysfunction and inflammation
THEN
--activated GIIb/IIIa glycoprotein + fibrinogen
--thrombus formation
classification of anti-platelet drug
1. Aspirin
---bokey, tapal
---inhibit cox-1 → reduce level of Thromboxane A2
---function of Thromboxane A2
(1) platelet shape change
(2) activation of GpⅡb/Ⅲa receptor → via fibrinogen
(3) promote dense granule to release Ca & ADP
2. GⅡb/Ⅲa antagonist
---Abciximab, Eptifibatide, Tirofiban
3. thienopyridenes
---Ticlopidine, clopidogrel
Aspirin
--irreversibly acetylating Cox-1
--reduece production of Thromboxane A2
--good cost-effective
--failed to prevent ACS in high risk patients
--prior use of aspirin. poor response to Aspirin during ACS attack
compared with naive to aspirin
--aspirin resistance?
Thienopyridenes
--inhibit ADP receptor (adenosine diphospate)
--would be activated by ADP, which was released from endothelial cell or RBC
--activated ADP receptor would stimulate
(1) platelet shape change
(2) activation of GpⅡb/Ⅲa receptor → via fibrinogen
(3) promote dense granule to release Ca & ADP
ADP receptor antagonist
--final step of platelet aggregation
--add to Aspirin + heparin
--no increase of ICH risk
--In NSTEMI patient, divided into 2 group
(1)medical Tx: no benifit from add of GpⅡb/Ⅲa antagonist
(2)need PCI: benefit from add of GpⅡb/Ⅲa antagonist
--response: dependent on the intesity of platelet aggregation inhibition
About drug resistance
(1)Aspirin
---genetic polymorphism: PLT receptor, (PIa2)
---inadequate dose
---oxidative stress(increased arachidonic acid perioxidation)
---NSAID (Ibuprofen) use before aspirin
---increased expression of Cox-1
(2)Thienopyridenes
---Genetic polymorphism
---plavix is prodrug, which is needed to metabolized by CYP3A4(statin)
---Dose statin impact the effect of plavix?? still unknown
---However, high dose statin imprved the prognosis of CAD
JAMA. Oct, 2004. Review
high risk in ACS
--elevated cardiac enzymes
==TnI > 0.05 ng/mL, CKMB > 3% of CK, CKMB > 16 mg/dL
--multiple episodes of chest pain
--current aspirin use
--previous revasculization
TIMI risk score: (TIMI = Thrombolysis in MI)
1. Age 65 years
2. Presence of at least three risk factors for CHD
risk factor方面
3. Prior coronary stenosis of 50 percent
4. Use of aspirin in prior seven days
history方面
5. Presence of ST segment deviation on admission ECG
6. At least two anginal episodes in prior 24 hours
7. Elevated serum cardiac biomarkers
admission後表現
poor prognositic factor
--ST elevation in aVR lead, in NSTEMI
Pathophysiology in ACS
--plaque rupture or erosion + subsequent thrombosis
--endothelial dysfunction and inflammation
THEN
--activated GIIb/IIIa glycoprotein + fibrinogen
--thrombus formation
classification of anti-platelet drug
1. Aspirin
---bokey, tapal
---inhibit cox-1 → reduce level of Thromboxane A2
---function of Thromboxane A2
(1) platelet shape change
(2) activation of GpⅡb/Ⅲa receptor → via fibrinogen
(3) promote dense granule to release Ca & ADP
2. GⅡb/Ⅲa antagonist
---Abciximab, Eptifibatide, Tirofiban
3. thienopyridenes
---Ticlopidine, clopidogrel
Aspirin
--irreversibly acetylating Cox-1
--reduece production of Thromboxane A2
--good cost-effective
--failed to prevent ACS in high risk patients
--prior use of aspirin. poor response to Aspirin during ACS attack
compared with naive to aspirin
--aspirin resistance?
Thienopyridenes
--inhibit ADP receptor (adenosine diphospate)
--would be activated by ADP, which was released from endothelial cell or RBC
--activated ADP receptor would stimulate
(1) platelet shape change
(2) activation of GpⅡb/Ⅲa receptor → via fibrinogen
(3) promote dense granule to release Ca & ADP
ADP receptor antagonist
--final step of platelet aggregation
--add to Aspirin + heparin
--no increase of ICH risk
--In NSTEMI patient, divided into 2 group
(1)medical Tx: no benifit from add of GpⅡb/Ⅲa antagonist
(2)need PCI: benefit from add of GpⅡb/Ⅲa antagonist
--response: dependent on the intesity of platelet aggregation inhibition
About drug resistance
(1)Aspirin
---genetic polymorphism: PLT receptor, (PIa2)
---inadequate dose
---oxidative stress(increased arachidonic acid perioxidation)
---NSAID (Ibuprofen) use before aspirin
---increased expression of Cox-1
(2)Thienopyridenes
---Genetic polymorphism
---plavix is prodrug, which is needed to metabolized by CYP3A4(statin)
---Dose statin impact the effect of plavix?? still unknown
---However, high dose statin imprved the prognosis of CAD