Summary of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

Grade of Recommendation	Clarity of Risk vs. Benefit	Methodological Strength of Supporting Evidence	Implications
1A	Clear	Randomized Clinical Trials (RCT) without important limitations	Strong recommendation; can apply to most patients in most circumstances without reservation
1C+	Clear	No RCTs but strong RCT results can be unequivocally extrapolated, or overwhelming evidence from observational studies	Strong recommendation; can apply to most patients in most circumstances
1B	Clear	RCTs with important limitations (inconsistent results, methodological flaws¨)	Strong recommendation; likely to apply to most patients
1C	Clear	Observational studies	Intermediate-strength recommendation; may change when stronger evidence is available
2A	Unclear	RCTs without important limitations	Intermediate-strength recommendation; best action may differ depending on circumstances or patients’ or societal values
2C+	Unclear	No RCTs but strong RCT results can be unequivocally extrapolated, or overwhelming evidence from observational studies	Weak recommendation; best action may differ depending on circumstances or patients’ or societal values
2B	Unclear	RCTs with important limitations (inconsistent results, methodological flaws)	Weak recommendation; alternative approaches likely to be better for some patients under some circumstances
2C	Unclear	Observational studies	Very weak recommendations; other alternatives might be equally reasonable

Since studies in category B and C are flawed, it is likely that most recommendations in these classes will be level 2. The following considerations will bear on whether the recommendation is Grade 1 or Grade 2: the magnitude and precision of the treatment effect; patients’ risk of the target event being prevented; the nature of the benefit and the magnitude of the risk associated with treatment; variability in patient preferences; variability in regional resource availability and health-care delivery practice; and cost considerations. Inevitably, weighing these considerations involves subjective judgment.

¨ These situations include RCTs with both lack of blinding and subjective outcomes, where the risk of bias in measurement of outcomes is high, or RCTs with large loss to follow-up.

Antithrombotic Therapy for Coronary Artery Disease

CHEST 2004; 126:513S-548S

Acute Management of Non-ST-Elevation Acute Coronary Syndromes (NSTE ACS)
*Therapy*	*Details*	*Recommendation*	*Grade*
Antiplatelet Therapies	Without clear allergy to Aspirin	Aspirin (Immediate) 75 – 325 mg PO Aspirin (Daily) 75 – 162 mg	1A
	With Aspirin allergy	Clopidogrel (Immediate) 300 mg Clopidogrel (Daily) 75 mg	1A
	Diagnostic catheterization will be delayed or CABG will not occur until > 5 days following coronary angiography	Clopidogrel (Immediate) 300 mg Clopidogrel (Daily) 75 mg x 9 – 12 months + Aspirin (Daily) 75 – 162 mg	1A
	Angiography will take place rapidly (£ 24 hours)	Clopidogrel (after coronary atomy has been determined)	2A
	Patients having received Clopidogrel and are scheduled to undergo CABG	Discontinue Clopidogrel 5 days prior to scheduled surgery	2A
Glycoprotein IIb/IIIa Inhibitors	Moderate-to high-risk patients presenting with NSTE ACS	Eptifibatide or Tirofiban (initial treatment) + Aspirin + Heparin	1A
	Moderate-to high-risk patients presenting with NSTE ACS who are also receiving Clopidogrel	Eptifibatide or Tirofiban (additional initial treatment)	2A
	All patients presenting with NSTE ACS	*Against* Abciximab as initial treatment except when coronary anatomy is known and PCI planned within 24 hours	1A
Antithrombin Therapies	All patients presenting with NSTE ACS	Unfractionated heparin (UFH) recommended over no Heparin for short term use with antiplatelet therapies	1A
	All patients presenting with NSE ACS who are then prescribed IV Heparin	Weight based dosing of UFH and maintenance of aPTT between 50s and 75s	1C+
	Acute treatment of NSTE ACS	Low Molecular Weight Heparins (LMWH) recommended over UFH	1B
	Patients receiving LMWHs with NSTE ACS	*Against* routine monitoring of anticoagulant effect of LMWHs	1C
	Patients receiving LMWHs with NSTE ACS	Continue LMWH during PCI treatment	2C
	Patients receiving GP IIb/IIIa inhibitors as upstream treatment of NSTE ACS	LMWH recommended over UFH as the anticoagulant of choice	2B
	Patients presenting with NSTE ACS	*Against* Direct Thrombin Inhibitors (DTIs) as routine initial antithrombin therapy	1B
Post-Myocardial Infarction and Post-ACS
*Therapy*	*Details*	*Recommendation*	*Grade*
Antiplatelet Therapies	ACS with and without ST-segment elevation	Aspirin (Initial) 160 – 325 mg Aspirin (Indefinite) 75 – 162 mg daily	1A
	Patients with a history of Aspirin –induced bleeding or with risk factors for bleeding	Aspirin £ 100 mg daily	1C+
	Aspirin is contraindicated or not tolerated	Clopidogrel (Long-term) 75 mg daily	1A
Comparison of Antiplatelet and Anticoagulant Therapy and/or Combinations of Aspirin and Warfarin Trials	Most health-care settings, for moderate- and low-risk patients with a myocardial infarction	Aspirin alone recommended over Oral Vitamin K Antagonists (VKA) plus Aspirin	2B
	In health-care settings in which meticulous INR monitoring is standard and routinely accessible, for both high- and low-risk patients after MI	Long-term (up to 4 years) high-intensity oral VKAs (target INR 3.5; range 3.0 – 4.0) without concomitant Aspirin or Moderate-intensity oral VKAs (target INR 2.5; range 2.0 – 3.0) plus Aspirin	2B
	High-risk patients with MI, including those with large anterior MI, those with significant heart failure, those with intracardiac thrombus visible on echocardiography, and those with a history of a thromboembolic event	Combined use of moderate-intensity oral VKAs (INR 2.0 – 3.0) plus low dose Aspirin (£ 100 mg daily) for 3 months after the MI	2A
Chronic, Stable CAD
*Therapy*	*Details*	*Recommendation*	*Grade*
Antiplatelet Therapies	All patients with chronic, stable CAD	Aspirin 75 – 162 mg daily	1A
	All patients with chronic, stable CAD	Continue Aspirin indefinitely	2C
	Stable, chronic coronary disease with a risk profile indicating a high likelihood of development of AMI	Clopidogrel (Long-term) plus Aspirin	2C
Vitamin K Antagonists	Patients with chronic, stable CAD without prior MI	*Against* long-term oral VKAs	2C
Congestive Heart Failure With and Without CAD
*Therapy*	*Details*	*Recommendation*	*Grade*
VKA, Aspirin	CHF due to nonischemic etiology	*Against* routine use of Aspirin or oral VKAs	1B
VKA, Aspirin	Patients with CHF requiring Aspirin	Aspirin, regardless of whether the patient is receiving an ACE-Inhibitor	1C+
Primary Prevention
*Therapy*	*Details*	*Recommendation*	*Grade*
Aspirin, VKA, or Both	Patients with at least moderate risk for a coronary event (based on age and cardiac risk factor profile with a 10-year risk of a cardiac event of > 10%)	Aspirin 75 – 162 mg daily recommended over no antithrombotic therapy	2A
		Aspirin 75 – 162 mg daily recommended over VKAs	2A
	Patients at particularly high risk of events in whom the INR can be monitored without difficulty	Low-dose VKAs with target INR of approximately 1.5	2A
Thrombolysis and Adjunctive Therapy in Acute Myocardial Infarction CHEST 2004;126:549S-575S
Patients with Acute Myocardial Infarction: Thrombolysis
*Therapy*	*Details*	*Recommendation*	*Grade*
Thrombolysis with Streptokinase, t-PA, Anistreplase, Reteplase, and Tenecteplase	Patients with ischemic symptoms characteristic of acute MI £ 12 hours in duration, and ST-segment elevation or left bundle-branch block (of unknown duration) on ECG	Any approved fibrinolytic agent	1A
		Recommended: Streptokinase, Anistreplase, Reteplase, Alteplase, Tenecteplase	1A
	Patients with symptom duration £ 6 hours	Administration of Alteplase or Tenecteplase recommended over Streptokinase	1A
	Patients with known allergy or sensitivity to Streptokinase	Alteplase, Reteplase, Tenecteplase	1A
	Patients with recurrent acute myocardial infarction	*Do not* use repeat administration of Streptokinase	2C
	Patients with ischemic symptoms characteristic of acute MI of £ 12 hours in duration and 12-lead ECG findings consistent with a true posterior MI	Fibrinolytic therapy	2C
	High-risk patients with ongoing symptoms characteristic of acute MI or hemodynamic compromise and duration of 12 – 24 hours who have ST elevation or left bundle-branch block	Administration of IV fibrinolytic therapy	2B
	Health-care settings where prehospital administration of fibrinolytic therapy is feasible and primary angioplasty is not available	Prehospital administration of fibrinolytic therapy only	1A
	Patients with acute MI who are candidates for fibrinolytic therapy	Administration within 30 minutes of arrival to the hospital or first contact with the health-care system	1A
	Patients with any history of intracranial hemorrhage, closed head trauma, or ischemic stroke within the past 3 months	*Against* administration of fibrinolytic therapy	1C+
Adjunctive Treatment with Antithrombotic Agents in Patients Receiving Fibrinolysis for Acute Myocardial Infarction
*Therapy*	*Details*	*Recommendation*	*Grade*
Adjunctive Treatment with Aspirin	Patients with acute ST elevation MI, whether or not they receive fibrinolytic therapy	Aspirin 160 – 325 mg PO at initial evaluation, then indefinite therapy (75 – 162 mg PO daily)	1A
Adjunctive Treatment with Clopidogrel	Patients with allergy to Aspirin	Clopidogrel—loading dose (300 mg PO), maintenance dose (75 mg PO daily)	2C
Adjunctive Treatment with Unfractionated Heparin	Patients receiving Streptokinase	IV UFH 5000 unit bolus 1000 units/hr (patients > 80 kg) 800 units/hr (patients < 80 kg) Target aPTT of 50 – 75 seconds	2C
	Patients receiving Streptokinase	SC UFH 12,500 units Q12H for 48 hours	2A
	All patients with high risk of systemic or venous thromboembolism (anterior MI, pump failure, previous embolus, atrial fibrillation, or left ventricular thrombus)	Administration of IV UFH while receiving streptokinase	1C+
	Patients receiving Alteplase, Tenecteplase, Reteplase for fibrinolysis in acute MI	Administration of weight-adjusted heparin (60 units/kg bolus—maximum 4000 units) followed by 12 units/kg/hour (1000 units/hour maximum) adjusted to maintain aPTT 50 – 75 seconds for 48 hours	1C
Adjunctive Treatment with LMWH	Patients aged £ 75 years with preserved renal function (creatinine £ 2.5 mg/dL in males and £ 2.0 mg/dL in females)	Enoxaparin (30 mg bolus IV followed by 1 mg/kg SC Q12H) with Tenecteplase up to 7 days	2B
Adjunctive Therapy with Glycoprotein IIb/IIIa Receptor Blockers	Patients with acute ST elevation MI	Recommend *against* the combinations: Standard-dose Abciximab + ½-dose Reteplase OR ½-dose Tenecteplase + low-dose IV UFH OVER Standard-dose Reteplase or Tenecteplase	1B
	Patients with acute ST elevation MI	Suggest clinicians not use the combination: Streptokinase + any GP IIb/IIIa inhibitor	2B
Adjunctive Therapy with Direct Thrombin Inhibitors	Patients with acute ST-elevation MI treated with Streptokinase	*Do not* use Bivalirudin routinely	2A
	Patients with known or suspected heparin-induced thrombocytopenia (HIT) who are receiving fibrinolytic therapy	Administration of Hirudin with tPA	1A
		Administration of Bivalirudin with Streptokinase	2A
Antithrombotic Therapy During Percutaneous Coronary Intervention (PCI) CHEST 2004;126:576S-599S
Patients Undergoing PCI: Oral Antiplatelet Therapy
*Therapy*	*Details*	*Recommendation*	*Grade*
Aspirin	Patients undergoing PCI	Pretreatment with Aspirin, 75 – 325 mg	1A
	Long-term treatment after PCI	Aspirin 75 – 162 mg daily	1A
	Long-term treatment after PCI in patients who receive antithrombotic agents such as Clopidogrel or Warfarin	Lower-dose Aspirin (75 – 100 mg daily)	1C+
Ticlopidine Versus Clopidogrel After Stent Placement	Patients who underwent stent placement	Combination of Aspirin and a thienopyridine derivative (Clopidogrel or Ticlopidine) over systemic anticoagulation	1A
	Patients who underwent stent placement	Clopidogrel recommended over Ticlopidine	1A
		Clopidogrel loading dose (300 mg) 6 hours prior to planned PCI	1B
	If Clopidogrel started < 6 hours prior to PCI	Clopidogrel loading dose of 600 mg	2C
	If Ticlopidine is administered	Loading dose of 500 mg at least 6 hours before planned PCI	2C
Aspirin Intolerant Patients	PCI patients who cannot tolerate aspirin	Loading dose of Clopidogrel (300 mg) or Ticlopidine (500 mg) be administered at least 24 hours prior to planned PCI	2C
Duration of Thienopyridine Therapy After Stent Placement	After PCI, in addition to Aspirin	Clopidogrel (75 mg daily) for at least 9 – 12 months	1A
	If Ticlopidine is used in place of Clopidogrel after PCI	Ticlopidine for 2 weeks after placement of a bare metal stent in addition to Aspirin	1B
	Patients with low atherosclerotic risk, such as those with isolated coronary lesions	Clopidogrel for at least 2 weeks after placement of a bare metal stent	1A
		Clopidogrel for 2 – 3 months after placement of a Sirolimus-eluting stent	1C+
		Clopidogrel for 6 months after placement of a Paclitaxel-eluting stent	1C
Other Oral Antiplatelet Agents	Patients after stent placement	Ticlopidine over Cilostazol	1B
	Patients after stent placement	Clopidogrel over Cilostazol	1C
	Aspirin-intolerant patients undergoing PCI	*Do not* use Dipyridamole as an alternative to thienopyridine therapy	2C
Patients Undergoing PCI: GP IIb/IIIa Inhibitors
*Therapy*	*Details*	*Recommendation*	*Grade*
GP IIb/IIIa Inhibitors GP IIb/IIIa Inhibitors	All patients undergoing PCI, particularly for those undergoing primary PCI, or those with refractory unstable angina or other high-risk features	Use of a GP IIb/IIIa antagonist (Abciximab or Eptifibatide)	1A
	Patients undergoing PCI for STEMI	Abciximab recommended over Eptifibatide (Remark: whenever possible, Abciximab should be started prior to balloon inflation)	1B
	All patients undergoing PCI (Abciximab dosing)	Abciximab as a 0.25 mg/kg bolus followed by a 12-hour infusion at a rate of 10 mcg/min	1A
	All patients undergoing PCI (Eptifibatide dosing)	Eptifibatide as a double bolus (each 180 mcg/kg administered 10 minutes apart) followed by an 18-hour infusion of 2.0 mcg/kg/min	1A
	Patients undergoing PCI	*Against* use of Tirofiban as an alternative to Abciximab	1A
	Patients with NSTEMI/UA who are designated as moderate-to-high risk based on TIMI score	Upstream use of a GP IIb/IIIa antagonist (either Eptifibatide or Tirofiban) started as soon as possible prior to PCI	1A
	Patients with NSTEMI/UA who receive upstream treatment with Tirofiban	PCI be deferred for at least 4 hours after initiating Tirofiban infusion	2C
	Patients with planned PCI in NSTEMI/UA patients with an elevated troponin level	Abciximab be started within 24 hours prior to the intervention	1A
Patients Undergoing PCI: Unfractionated Heparin
*Therapy*	*Details*	*Recommendation*	*Grade*
Unfractionated Heparin	Patients receiving a GP IIb/IIIa inhibitor	Heparin bolus (50 – 70 units/kg) to achieve target ACT > 200 s	1C
	Patients not receiving GP IIb/IIIa inhibitor	Heparin be administered in doses sufficient to produce an ACT 250 – 350 s	1C+
		Weight-adjusted Heparin bolus of 60 – 100 units/kg	2C
	Patients after uncomplicated PCI	*Against* routine postprocedural infusion of Heparin	1A
Patients Undergoing PCI: LMWH
*Therapy*	*Details*	Recommendation	*Grade*
Low Molecular Weight Heparin	Patients who have received LMWH prior to PCI	Administration of additional anticoagulant therapy is dependent on the timing of the last dose of LMWH	1C
	If the last dose of Enoxaparin was administered £ 8 hours prior to PCI	No additional anticoagulant therapy	2C
	If the last dose of Enoxaparin was administered between 8 and 12 hours before PCI	0.3 mg/kg bolus of IV Enoxaparin at the time of PCI	2C
	If the last dose of Enoxaparin was administered > 12 hours before PCI	Conventional anticoagulation therapy during PCI	2C
Patients Undergoing PCI: Direct Thrombin Inhibitors
*Therapy*	*Details*	*Recommendation*	*Grade*
Direct Thrombin Inhibitors	Patients undergoing PCI who are not treated with a GP IIb/IIIa antagonist	Bivalirudin (0.75 mg/kg bolus followed by an infusion of 1.75 mg/kg/hour for the duration of PCI) over Heparin during PCI	1A
	In PCI patients who are at low risk for complications	Bivalirudin as an alternative to Heparin as an adjunct to GP IIb/IIIa antagonists	1B
	In PCI patients who are at high risk for bleeding	Bivalirudin over Heparin as an adjunct to GP IIb/IIIa antagonists	1B
Patients Undergoing PCI: Vitamin K Antagonists
*Therapy*	*Details*	*Recommendation*	*Grade*
Vitamin K Antagonists	Patients undergoing PCI with no other indication for systemic anticoagulation therapy	*Against* routine use of Warfarin (or other Vitamin K antagonist) after PCI	1A
Antithrombotic Therapy in Atrial Fibrillation CHEST 2004;126:429S-456S
Long-Term Antithrombotic Therapy for Chronic Atrial Fibrillation (AF) or Atrial Flutter, Anticoagulants and Antiplatelet Agents
*Disease State*	*Details*	*Recommendation*	*Grade*
Atrial Fibrillation	Patients with persistent (“sustained” or “permanent”) or paroxysmal (intermittent) AF at high risk of stroke (having any of the following features: prior ischemic stroke, TIA, systemic embolism, age > 75 years, moderately or severely impaired left ventricular systolic function and/or congestive heart failure, history of hypertension, or diabetes mellitus)	Anticoagulation with an oral VKA, such as Warfarin (Target INR 2.5; Range 2.0 – 3.0)	1A
	Patients with persistent AF or PAF, age 65 – 75 years, in the absence of other risk factors	Antithrombotic therapy: Oral VKA, such as Warfarin (Target INR 2.5; Range 2.0 – 3.0) OR Aspirin 325 mg daily	1A
	Patients with persistent AF or PAF < 65 years old and with no other risk factors	Aspirin 325 mg daily	1B
Atrial Flutter	Patients with atrial flutter	Antithrombotic therapy decisions follow the same risk-based recommendations as for AF	2C
Valvular Heart Disease and Atrial Flutter	Patients with AF and mitral stenosis	Anticoagulation with an oral VKA, such as Warfarin (Target INR 2.5; Range 2.0 – 3.0)	1C+
Valvular Heart Disease and Atrial Flutter	Patients with AF and prosthetic heart valves	Anticoagulation with an oral VKA, such as Warfarin	1C+
Atrial Fibrillation Following Cardiac Surgery	AF occurring shortly after open-heart surgery and lasting > 48 hours	Anticoagulation with an oral VKA, such as Warfarin, if bleeding risks are acceptable Target INR 2.5 (Range 2.0 – 3.0)	2C
Atrial Fibrillation Following Cardiac Surgery		Continue anticoagulation for several weeks following reversion to NSR, particularly if patients have risk factors for thromboembolism	2C
Anticoagulation for Elective Cardioversion of Atrial Fibrillation or Atrial Flutter Patients
*Disease State*	*Details*	*Recommendation*	*Grade*
Atrial Fibrillation *Comment: For all, continuation of anticoagulation beyond 4 weeks is based on whether the patient has experienced more than one episode of AF and on their risk factor status. Patients experiencing more than one episode of AF should be considered as having PAF. Atrial Fibrillation	AF of ³ 48 hours or of unknown duration for whom pharmacologic or electrical cardioversion is planned	Anticoagulation with an oral VKA, such as Warfarin (Target INR 2.5; Range 2.0 – 3.0), for 3 weeks before elective cardioversion and for at least 4 weeks after successful cardioversion	1C+
		Immediate UFH with target PTT of 60 s (range 50 – 70 s) or at least 5 days of Warfarin with target INR of 2.5 (2.0 – 3.0) and a screening multiplane TEE. If no thrombus seen and cardioversion successful, anticoagulation with Warfarin (Target 2.5; Range 2.0 – 3.0) for at least 4 weeks	1B
	Multiplane TEE performed and thrombus visualized	Cardioversion should be postponed and anticoagulation should be continued indefinitely; Obtain repeat TEE before attempting later cardioversion	1B
	Patients with AF of known duration < 48 hours	Cardioversion can be performed without anticoagulation	2C
	Patients with AF of known duration < 48 hours and no known contraindication to anticoagulation	IV Heparin (Target PTT 60 s; range 50 – 70 s), or LMWH (at full DVT treatment doses) at presentation	2C
	Emergency cardioversion where a TEE-guided approach is not possible	IV UFH (target PTT 60 s; range 50 – 70 s) started as soon as possible, followed by 4 weeks of anticoagulation with an oral VKA, such as Warfarin (target INR 2.5; range 2.0 – 3.0) if NSR persists after cardioversion	2C
Atrial Flutter	Patients with atrial flutter	Use of anticoagulants in the same way as for cardioversion of patients with Atrial Fibrillation	2C
Antithrombotic Therapy in Valvular Heart Disease—Native and Prosthetic CHEST 2004;126:457S-482S
*Disease State*	*Details*	*Recommendation*	*Grade*
Rheumatic Mitral Valve Disease with AF or a History of Systemic Embolism	Rheumatic mitral valve disease and AF, or a history of previous systemic embolism	Long term oral anticoagulant therapy Target INR 2.5; Range 2.0 – 3.0	1C+
		*Do not* use concomitant therapy with oral anticoagulants and antiplatelet agents	2C
	Rheumatic mitral valve disease with AF or a history of systemic embolism who suffer systemic embolism while receiving oral anticoagulants at a therapeutic INR	Add Aspirin, 75 – 100 mg daily	1C
		Patients unable to take Aspirin, add Dipyridamole 400 mg daily, or Clopidogrel	1C
Mitral Valve Disease in Sinus Rhythm	Rheumatic mitral valve disease and normal sinus rhythm with a left atrial diameter > 5.5 cm	Long-term VKA Target INR 2.5; Range 2.0 – 3.0	2C
Mitral Valve Disease in Sinus Rhythm	Rheumatic mitral valve disease and normal sinus rhythm with a left atrial diameter < 5.5 cm	*Do not* use antithrombotic therapy	2C
Mitral Valvuloplasty	Patients undergoing mitral valvuloplasty	Anticoagulation with VKA with a target INR of 2.5 (range 2.0 – 3.0) for 3 weeks prior to the procedure and 4 weeks after the procedure	2C
Mitral Valve Prolapse (MVP)
*Disease State*	*Details*	*Recommendation*	*Grade*
Mitral Valve Prolapse	Patients who have not experienced systemic embolism, unexplained TIAs, or AF	Against any antithrombotic therapy	1C
	Documented but unexplained TIAs	Long-term Aspirin therapy, 50 – 162 mg daily	1A
	Documented systemic embolism or recurrent TIAs despite aspirin therapy	Long-term VKA therapy (target INR 2.5; range 2.0 – 3.0)	2C
Mitral Annular Calcification (MAC)
*Disease State*	*Details*	*Recommendation*	*Grade*
Mitral Annular Calcification	Complicated by systemic embolism, not documented to be calcific embolism	Long-term VKA therapy (target INR 2.5; range 2.0 – 3.0)	2C
Aortic Valve and Aortic Arch Disorders
*Disease State*	*Details*	*Recommendation*	*Grade*
Aortic Valve Disease	Patients with aortic valve disease	*Do not* use long-term Vitamin K antagonist therapy unless there is another indication for anticoagulation	2C
Aortic Valve Disease	Mobile aortic atheromas and aortic plaques > 4mm as measured by TEE	Oral anticoagulant therapy	2C
Prosthetic Heart Valves—Mechanical Prosthetic Heart Valves
*Disease State*	*Details*	*Recommendation*	*Grade*
Mechanical Prosthetic Heart Valves Mechanical Prosthetic Heart Valves	All patients with mechanical prosthetic heart valves	Vitamin K Antagonists	1C+
	All patients with mechanical prosthetic heart valves	Administration of UFH or LMWH until the INR is stable at a therapeutic level for 2 consecutive days	2C
	St. Jude Medical bileaflet valve in the aortic position	Target INR of 2.5 (2.0 – 3.0)	1A
	Tilting disk valves and bileaflet mechanical valves in the mitral position	Target INR of 3.0 (2.5 – 3.5)	1C+
	CarboMedics bileaflet valve or Medtronic Hall tilting disk mechanical valves in the aortic position, normal left atrium size and sinus rhythm	Target INR of 2.5 (2.0 – 3.0)	1C+
	Mechanical valves and additional risk factors such as AF, myocardial infarction, left atrial enlargement, endocardial damage, and low ejection fraction	Target INR of 3.0 (2.5 – 3.5) combined with low doses of Aspirin (75 – 100 mg daily)	1C+
	Patients with caged ball or caged disk valves	Target INR 3.0 (2.5 – 3.5) in combination with Aspirin (75 – 100 mg daily)	2A
	Mechanical prosthetic heart valves who suffer systemic embolism despite a therapeutic INR	Maintenance of INR 3.0 (2.5 – 3.5) plus addition of Aspirin (75 – 100 mg daily)	1C+
	Prosthetic heart valves in whom VKA must be discontinued	LMWH or Aspirin 80 – 100 mg daily	1C
Prosthetic Heart Valves—Bioprosthetic Valves
*Time Frame*	*Details*	*Recommendation*	*Grade*
First 3 Months After Valve Insertion	Bioprosthetic valve in the mitral position	VKAs; Target INR 2.5 (range 2.0 – 3.0) for the first 3 months after valve insertion	1C+
	Bioprosthetic valve in the aortic position	VKAs; Target INR 2.5 (2.0 – 3.0) for the first 3 months after valve insertion	2C
	Bioprosthetic valve in the aortic position	Aspirin 80 – 100 mg daily	1C
	Patients who have undergone valve replacement	Heparin (LMWH or UFH) until the INR is stable at therapeutic levels for 2 consecutive days	2C
	Patients with bioprosthetic valves who have a history or systemic embolism	VKAs for 3 – 12 months	1C
	Patients with bioprosthetic valves who have evidence of a left atrial thrombus at surgery	VKAs with a dose sufficient to prolong the INR to a target of 2.5 (range 2.0 – 3.0)	1C
Long-Term Treatment	Patients with bioprosthetic valves who have AF	Long-term treatment with VKAs with a target INR of 2.5 (range 2.0 – 3.0)	1C+
Long-Term Treatment	Patients with bioprosthetic valves who are in sinus rhythm and do not have AF	Long-term therapy with Aspirin, 75 – 100 mg daily	1C+
Infective Endocarditis and Nonbacterial Thrombotic Endocarditis
*Disease State*	*Details*	*Recommendation*	*Grade*
Endocarditis	Mechanical prosthetic valve and endocarditis who have no contraindications	Continuation of long-term Vitamin K Antagonists	2C
	Patients with nonbacterial thrombotic endocarditis and systemic or pulmonary emboli	Full-dose IV UFH or SQ Heparin	1C
	Disseminated cancer or debilitating disease with aseptic vegetations	Full-dose UFH	2C
Prevention of Venous Thromboembolism CHEST 2004;126:338S-400S
General Recommendations
*Situation*	*Details*	*Recommendation*	*Grade*
Mechanical Prophylaxis	Mechanical methods of prophylaxis including graduated compression stockings (GCS), the use of intermittent pneumatic compression (IPC) devices and the venous foot pump (VFP)	Used primarily in patients who are at high risk of bleeding	1C+
		Used as an adjunct to anticoagulant-based prophylaxis	2A
		Careful attention be directed toward ensuring the proper use of, and optimal compliance with, the mechanical device	1C+
Aspirin for Prophylaxis	Any patient group	*Against* the use of Aspirin alone as prophylaxis against VTE	1A
Dosing	For each of the antithrombotic agents	Clinicians consider the manufacturer’s suggested dosing guidelines	1C
Renal Impairment	All patients, particularly elderly patients and those who are at high risk for bleeding	Consider renal impairment when deciding on doses of LMWH, Fondaparinux, the direct thrombin inhibitors and other antithrombotic drugs that are cleared by the kidneys	1C+
Neuraxial Anesthesia	All patients undergoing neuraxial anesthesia or analgesia	Special caution when using anticoagulant prophylaxis	1C+
General, Vascular, Gynecologic and Urologic Surgery
*Surgery Type*	*Details*	*Recommendation*	*Grade*
General Surgery	Low risk general surgery patients Low risk—minor surgery in patients < 40 yr with no additional risk factors	*Against* use of specific prophylaxis other than early and persistent mobilization	1C+
	Moderate risk general surgery patients Moderate risk—nonmajor procedure in patients 40 – 60 yrs or < 40 yrs with additional risk factors or patients undergoing major operations and are < 40 yrs of age with no additional risk factors	Prophylaxis with LDUH 5000 units BID or LMWH £ 3400 units once daily	1A
	Higher risk general surgery patients Higher risk—nonmajor surgery and > 60 years of age or additional risk factors or patients undergoing major surgery who are > 40 year of age or have additional risk factors	Prophylaxis with LDUH 5000 units TID or LMWH > 3400 units daily	1A
	High risk general surgery patients with multiple risk factors	Pharmacologic methods (LDUH TID or LMWH > 3400 units daily) be combined with use of GCS and/or IPC	1C+
	General surgery patients with high risk of bleeding	Mechanical prophylaxis with properly fitted GCS or IPC, at least initially until the bleeding risk decreases	1A

CHEST 2004; 126:513S-548S

Post-Myocardial Infarction and Post-ACS

Thrombolysis and Adjunctive Therapy in Acute Myocardial Infarction

CHEST 2004;126:549S-575S

CHEST 2004;126:576S-599S

Recommendation