Antithrombotic Therapy for Coronary Artery Disease

Antithrombotic Therapy for Coronary Artery Disease. (Update 2005-2006)

Adapted from 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy, Chest 2004.

Antithrombotic Therapy for Coronary Artery Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Robert A. Harrington, Richard C. Becker, Michael Ezekowitz, Thomas W. Meade, Christopher M. O'Connor, David A. Vorchheimer, and Gordon H. Guyatt
Chest 126: 513S-548S.

Thrombolysis and Adjunctive Therapy in Acute Myocardial Infarction: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Venu Menon, Robert A. Harrington, Judith S. Hochman, Christopher P. Cannon, Shaun D. Goodman, Robert G. Wilcox, Holger J. Sch?nemann, and E. Magnus Ohman
Chest 126: 549S-575S.

Antithrombotic Therapy During Percutaneous Coronary Intervention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Jeffrey J. Popma, Peter Berger, E. Magnus Ohman, Robert A. Harrington, Cindy Grines, and Jeffrey I. Weitz
Chest 126: 576S-599S.

ST Elevation MI within 12 hours ( include new or Unknown duration LBBB and true posterior MI)
Thrombolytic agents † Antiplatelet Antithrombin
ASA Clopidogrel GP IIb/IIIa receptor blockers UFH LMWH
• Not use in closed head trauma, ischemic stroke within 3 months.
• Streptokinase (Not use: when MI is >6 h or repeatedly or history of allergy).
• Alteplase,
• Reteplase,
• Tenecteplase.
• Thrombolytic therapy should be within 30 min. • Immediate dose of 75 - 325 mg PO. Maintenance dose of 75-162 mg PO daily. • When there is ASA allergic history
• Immediate dose of 300 mg PO. Maintenance dose of 75 mg PO daily. • No combination of Streptokinase and IIb/IIIa.
• No combination of standard dose Abciximab and half-dose of Reteplase
• Abciximab and Eptifibatide are approved with PCI.
• Eptifibatide and Tirofiban are approved for non PC I- ACS. • With Streptokinase
5000 U IV bolus followed by 1000 U/h infusion for patients > 80 kg, and 800 U/h for patients < 80 kg. - Target PTT of 50-75 sec.
For 48 h.
• With other thrombolytic
Weight-adjusted dose of 60 U/kg IV bolus (maximum of 4000 U) followed by 12 U/kg/h infusion (maximum of 1000 U/h). Target PTT of 50-75 sec.
For 48 h. .
Non ST Elevation ACS
Thrombolytic agents Antiplatelet Antithrombin
ASA Clopidogrel GP IIb/IIIa receptor blockers UFH LMWH
. • Immediate dose of 75 - 325 mg PO.
• Maintenance dose of 75-162 mg PO daily. • When there is ASA allergic history or when cardiac catheterization or cardiac surgery will be delayed.
• Immediate dose of 300 mg PO. Maintenance dose of 75 mg PO daily.
• In moderate-high risk patients. *
• Eptifibatide or Tirofiban (not Abciximab) in addition to other antithrombotic therapy.
• Weight-based dosing and maintaining PTT of 50-75 sec. • Favor LMWH over UFH.
• Enoxaparin 1 mg/kg SC every 12 hrs for 48 hr or more.
• Do not use if Cr cl < 30 ml/min
† = Include high risk patients with ongoing ischemic symptoms or hemodynamic compromise during 12-24 hours.
* = Short term risks of death or nonfatal MI in patients with unstable angina (Table below)

. High
(At least one of the following features must be present) Intermediate
(No high risk features but must have one of the following features) Low
(No high or intermediate risk features but may have any of the following features)
History Accelerate ischemic symptoms in preceding 48 hr. Prior MI, peripheral or cerebrovascular disease, CABG, prior ASA use. .
Chest pain Ongoing rest pain >20 min Rest pain >20 min, now resolved.
Rest pain <20 min or relieved with rest or sublingual nitroglycerin New onset or progressive CCS class III or IV angina in the past 2 weeks.
Clinical >75 yo, pulmonary edema, new or worsening heart murmur, S3 or new/worsening rales, hypotension, bradycardia, tachycardia. <70 yo .
ECG Transient ST- segment changes (>0.05 mV), new or presumed new BBB, sustained ventricular tachycardia. T-wave inversion >0.2 mV.
Pathologic Q wave. Normal or unchanged ECG during episode of chest pain
Cardiac markers Elevated troponin Mildly elevated troponin (eg, < 0.1) Normal
• UFH = Unfractionate Heparin. LMWH = Low Molecular Weight Heparin.
• Antiplatelet: ASA; COX-1 and COX-2 inhibitors; Dipyridamole; Thienopyridines; GPIIb/IIIa Receptor Antagonists.
• Thienopyridines: Ticlopidine (Ticlid ); Clopidogrel (Plavix).
• GP IIb/IIIa inhibitors: Abciximab (Reopro); Tirofiban (Aggrastat); Eptifibatide (Integrilin)

During PCI
Thrombolytic agents Antiplatelet Antithrombin
ASA Clopidogrel GP IIb/IIIa receptor blockers UFH LMWH
• Pre PCI with ASA 75-325 mg PO.
• Post PCI with ASA 75-162 mg PO daily. • Recommending Clopidogrel over Ticlopidine.
• < 6 h before PCI, use 600 mg PO.
• > 6 h before PCI, use 300 mg PO.
(• Dose of Ticlopidine is 500 mg. PO 6 h before PCI.)
• Should give Abcixibab ‡ or Eptifibatide at the beginning of PCI procedure.
• PCI for STEMI. Recommending Abciximab over Eptifibatide.
• In NSTEMI, if treated with Tirofiban, PCI should be delayed for 4 hours.
• With IIb/IIIa, use UFH at dose of 50-70 IU/kg. Target ACT of >200 s.
• Without IIb/IIIa, UFH at dose of 60-100 IU. Target ACT of 250-350 s.
• No post PCI heparin. • LMWH < 8 h, no more heparin.
• LMWH 8-12 h, additional dose of 0.3 mg/kg IV.
• LMWH >12 h, use standard dose of heparin therapy.
Following PCI
Thrombolytic agents Antiplatelet Antithrombin
ASA Clopidogrel GP IIb/IIIa receptor blockers UFH LMWH
. 75-161 mg PO daily. • In high risk patients. 75 mg PO daily for 9-12 months.
• For low risk patients.
(1) 3 months after Sirolimus-eluting stent.
(2) 6 months after Paclitaxel-eluting stent.
. • No post PCI heparin. .
‡ Abciximab dose is 0.25 mg/kg bolus followed by 12 h infusion at rate of 10 microgram/min Eptifibatide dose is double bolus of 180 microgram/kg each 10 minutes apart, followed by 18 h infusion of 2.0 microgram/kg/min.

• UFH = Unfractionate Heparin. LMWH = Low Molecular Weight Heparin.
• Antiplatelet: ASA; COX-1 and COX-2 inhibitors; Dipyridamole; Thienopyridines; GPIIb/IIIa Receptor Antagonists.
• Thienopyridines: Ticlopidine (Ticlid ); Clopidogrel (Plavix).
• GPIIb/IIIa inhibitors: Abciximab (Reopro); Tirofiban (Aggrastat); Eptifibatide (Integrilin)
Post MI and Post ACS *
Thrombolytic agents Antiplatelet Antithrombin
ASA Clopidogrel GP IIb/IIIa receptor blockers UFH LMWH
• Maintenance dose of 75-162 mg PO daily. • When there is ASA allergic history or in high risk patients in dose of 75 mg PO daily.
Chronic, Stable CAD *
Thrombolytic agents Antiplatelet Antithrombin
ASA Clopidogrel GP IIb/IIIa receptor blockers UFH LMWH
. Long term daily dose of 75-162 mg PO. Long term daily dose of 75 mg along with ASA in high risk patients. . .
Congestive Heart Failure with or without CAD
Thrombolytic agents Antiplatelet Antithrombin
ASA Clopidogrel GP IIb/IIIa receptor blockers UFH LMWH
Long term daily dose of 75-162 mg PO daily only in ischemic heart disease.
* Oral anticoagulation (VKAs) in post MI patients (large anterior MI, significant heart failure, LV thrombus, history of thromboembolic event. Use medium intensity (INR 2.5) with low dose ASA for 3 months.

• UFH = Unfractionate Heparin. LMWH = Low Molecular Weight Heparin.
• Antiplatelet: ASA; COX-1 and COX-2 inhibitors; Dipyridamole; Thienopyridines; GPIIb/IIIa Receptor Antagonists.
• Thienopyridines: Ticlopidine (Ticlid ); Clopidogrel (Plavix).
• GPIIb/IIIa inhibitors: Abciximab (Reopro); Tirofiban (Aggrastat); Eptifibatide (Integrilin)
Thrombolytic dose *

. Brand Name Initial Follow up
Streptokinase Streptase 1.5 million unit IV over 30-60 min
Alteplase Activase, tPA
(Total dose not >100 mg in 90 min) 15 mg IV bolus 0.75 mg/kg IV over 30 min (maximum 50 mg) 0.5 mg/kg over the next 60 min (maximum 35 mg)
Reteplase Retavase, rPA 10 unit IV over 2 min 2nd dose of 10 unit IV over 2 min, 30 min after the 1st dose. .
Tenecteplase
TNK IV over 10-15 sec
• <60 kg - 30 mg
• 60-69 kg - 35 mg
• 70-79 kg - 40 mg
• 80-89 kg - 45 mg
• >90 kg - 50 mg . .
* = ACC/AHA Pocket Guideline. Management of Patient With ST-Elevation Myocardial Infarction, 2004

GP IIb/IIIa dose
. Brand Name 1 ry PCI. ST-Elevation Myocardial Infarction * Unstable Angina and Non ST-Elevation Myocardial Infarction †
Abciximab Reopro • 10-60 min before PCI
• Bolus 0.25 mg/kg
• Infusion 0.125 microgm/kg/min (maximum 10 microgm/kg/min) for 12-18 hr
• Bolus 0.25 mg/kg
• Infusion 0.125 microgm/kg/min (maximum 10 microgm/kg/min) for 12-24 hr
Tirofiban Aggrastat • Bolus 10 microgm/kg
• Infusion 0.15 microgm/kg/min for 18-24 hr • 0.4 microgm /kg/min for 30 min followed by
• Infusion 0.1 microgm/kg/min for 48-96 hr
Eptifibatide Integrilin • 1st bolus 180 microgm/kg followed by
• Infusion 2.0 microgm/kg/min for 18-24 hr
• 2nd bolus 180 microgm/kg 10 min after the 1st
• Bolus 180 microgm/kg followed by
• Infusion 2.0 microgm/kg/min for 72-96 hr
* = ACC/AHA Pocket Guideline. Management of Patients With ST-Elevation Myocardial Infarction, 2004
† = ACC/AHA Pocket Guideline. Management of Patients With Unstable Angina and Non-ST-Elevation Myocardial Infarction, 2002

ST Elevation MI within 12 hours ( include new or Unknown duration LBBB and true posterior MI)
Thrombolytic agents †	Antiplatelet			Antithrombin
Thrombolytic agents †	ASA	Clopidogrel	GP IIb/IIIa receptor blockers	UFH	LMWH
• Not use in closed head trauma, ischemic stroke within 3 months. • Streptokinase (Not use: when MI is >6 h or repeatedly or history of allergy). • Alteplase, • Reteplase, • Tenecteplase. • Thrombolytic therapy should be within 30 min.	• Immediate dose of 75 - 325 mg PO. Maintenance dose of 75-162 mg PO daily.	• When there is ASA allergic history • Immediate dose of 300 mg PO. Maintenance dose of 75 mg PO daily.	• No combination of Streptokinase and IIb/IIIa. • No combination of standard dose Abciximab and half-dose of Reteplase • Abciximab and Eptifibatide are approved with PCI. • Eptifibatide and Tirofiban are approved for non PC I- ACS.	• With Streptokinase 5000 U IV bolus followed by 1000 U/h infusion for patients > 80 kg, and 800 U/h for patients < 80 kg. - Target PTT of 50-75 sec. For 48 h. • With other thrombolytic Weight-adjusted dose of 60 U/kg IV bolus (maximum of 4000 U) followed by 12 U/kg/h infusion (maximum of 1000 U/h). Target PTT of 50-75 sec. For 48 h.	.
Non ST Elevation ACS
Thrombolytic agents	Antiplatelet			Antithrombin
Thrombolytic agents	ASA	Clopidogrel	GP IIb/IIIa receptor blockers	UFH	LMWH
.	• Immediate dose of 75 - 325 mg PO. • Maintenance dose of 75-162 mg PO daily.	• When there is ASA allergic history or when cardiac catheterization or cardiac surgery will be delayed. • Immediate dose of 300 mg PO. Maintenance dose of 75 mg PO daily.	• In moderate-high risk patients. * • Eptifibatide or Tirofiban (not Abciximab) in addition to other antithrombotic therapy.	• Weight-based dosing and maintaining PTT of 50-75 sec.	• Favor LMWH over UFH. • Enoxaparin 1 mg/kg SC every 12 hrs for 48 hr or more. • Do not use if Cr cl < 30 ml/min

.	High (At least one of the following features must be present)	Intermediate (No high risk features but must have one of the following features)	Low (No high or intermediate risk features but may have any of the following features)
History	Accelerate ischemic symptoms in preceding 48 hr.	Prior MI, peripheral or cerebrovascular disease, CABG, prior ASA use.	.
Chest pain	Ongoing rest pain >20 min	Rest pain >20 min, now resolved. Rest pain <20 min or relieved with rest or sublingual nitroglycerin	New onset or progressive CCS class III or IV angina in the past 2 weeks.
Clinical	>75 yo, pulmonary edema, new or worsening heart murmur, S3 or new/worsening rales, hypotension, bradycardia, tachycardia.	<70 yo	.
ECG	Transient ST- segment changes (>0.05 mV), new or presumed new BBB, sustained ventricular tachycardia.	T-wave inversion >0.2 mV. Pathologic Q wave.	Normal or unchanged ECG during episode of chest pain
Cardiac markers	Elevated troponin	Mildly elevated troponin (eg, < 0.1)	Normal

During PCI
Thrombolytic agents	Antiplatelet			Antithrombin
Thrombolytic agents	ASA	Clopidogrel	GP IIb/IIIa receptor blockers	UFH	LMWH
	• Pre PCI with ASA 75-325 mg PO. • Post PCI with ASA 75-162 mg PO daily.	• Recommending Clopidogrel over Ticlopidine. • < 6 h before PCI, use 600 mg PO. • > 6 h before PCI, use 300 mg PO. (• Dose of Ticlopidine is 500 mg. PO 6 h before PCI.)	• Should give Abcixibab ‡ or Eptifibatide at the beginning of PCI procedure. • PCI for STEMI. Recommending Abciximab over Eptifibatide. • In NSTEMI, if treated with Tirofiban, PCI should be delayed for 4 hours.	• With IIb/IIIa, use UFH at dose of 50-70 IU/kg. Target ACT of >200 s. • Without IIb/IIIa, UFH at dose of 60-100 IU. Target ACT of 250-350 s. • No post PCI heparin.	• LMWH < 8 h, no more heparin. • LMWH 8-12 h, additional dose of 0.3 mg/kg IV. • LMWH >12 h, use standard dose of heparin therapy.
Following PCI
Thrombolytic agents	Antiplatelet			Antithrombin
Thrombolytic agents	ASA	Clopidogrel	GP IIb/IIIa receptor blockers	UFH	LMWH
.	75-161 mg PO daily.	• In high risk patients. 75 mg PO daily for 9-12 months. • For low risk patients. (1) 3 months after Sirolimus-eluting stent. (2) 6 months after Paclitaxel-eluting stent.	.	• No post PCI heparin.	.

Post MI and Post ACS *
Thrombolytic agents	Antiplatelet			Antithrombin
Thrombolytic agents	ASA	Clopidogrel	GP IIb/IIIa receptor blockers	UFH	LMWH
	• Maintenance dose of 75-162 mg PO daily.	• When there is ASA allergic history or in high risk patients in dose of 75 mg PO daily.
Chronic, Stable CAD *
Thrombolytic agents	Antiplatelet			Antithrombin
Thrombolytic agents	ASA	Clopidogrel	GP IIb/IIIa receptor blockers	UFH	LMWH
.	Long term daily dose of 75-162 mg PO.	Long term daily dose of 75 mg along with ASA in high risk patients.	.		.
Congestive Heart Failure with or without CAD
Thrombolytic agents	Antiplatelet			Antithrombin
Thrombolytic agents	ASA	Clopidogrel	GP IIb/IIIa receptor blockers	UFH	LMWH
	Long term daily dose of 75-162 mg PO daily only in ischemic heart disease.

.	Brand Name	Initial	Follow up
Streptokinase	Streptase	1.5 million unit IV over 30-60 min
Alteplase	Activase, tPA (Total dose not >100 mg in 90 min)	15 mg IV bolus	0.75 mg/kg IV over 30 min (maximum 50 mg)	0.5 mg/kg over the next 60 min (maximum 35 mg)
Reteplase	Retavase, rPA	10 unit IV over 2 min	2nd dose of 10 unit IV over 2 min, 30 min after the 1st dose.	.
Tenecteplase	TNK	IV over 10-15 sec • <60 kg - 30 mg • 60-69 kg - 35 mg • 70-79 kg - 40 mg • 80-89 kg - 45 mg • >90 kg - 50 mg	.	.

.	Brand Name	1 ry PCI. ST-Elevation Myocardial Infarction *	Unstable Angina and Non ST-Elevation Myocardial Infarction †
Abciximab	Reopro	• 10-60 min before PCI • Bolus 0.25 mg/kg • Infusion 0.125 microgm/kg/min (maximum 10 microgm/kg/min) for 12-18 hr	• Bolus 0.25 mg/kg • Infusion 0.125 microgm/kg/min (maximum 10 microgm/kg/min) for 12-24 hr
Tirofiban	Aggrastat	• Bolus 10 microgm/kg • Infusion 0.15 microgm/kg/min for 18-24 hr	• 0.4 microgm /kg/min for 30 min followed by • Infusion 0.1 microgm/kg/min for 48-96 hr
Eptifibatide	Integrilin	• 1st bolus 180 microgm/kg followed by • Infusion 2.0 microgm/kg/min for 18-24 hr • 2nd bolus 180 microgm/kg 10 min after the 1st	• Bolus 180 microgm/kg followed by • Infusion 2.0 microgm/kg/min for 72-96 hr