Heparin Sodium and Warfarin Sodium

• Generic Name: heparin
• Dosage Forms: n.a.
• Other Brand Names: HepFlush, Hep-Pak, Heparin Lock flush, Hep-Pak CVC, Hep-Lock, Heparin Sodium ADD-Vantage

Treatment of DVT and PE.

Recommended by the American College of Chest Physicians (ACCP) as an appropriate choice of anticoagulant for initial treatment of acute proximal DVT or PE.

LMWHs or fondaparinux generally preferred over heparin for initial treatment of acute venous thromboembolism; however, heparin may be preferred in patients with renal impairment. IV heparin also may be preferred over sub-Q therapies in patients with PE in whom thrombolytic therapy is being considered or if there is concern about adequate sub-Q absorption.

After full-dose heparin therapy, warfarin or an LMWH generally is administered as follow-up anticoagulant therapy for ≥3 months in adults with venous thromboembolism.

Thromboprophylaxis in General Surgery

Prophylaxis of postoperative DVT and PE in patients undergoing general (e.g., abdominal) surgery who are at risk of thromboembolism.

ACCP recommends pharmacologic (e.g., low-dose heparin) and/or nonpharmacologic/mechanical (e.g., intermittent pneumatic compression) methods of thromboprophylaxis in patients undergoing general surgery, including abdominal, GI, gynecologic, and urologic surgery, according to the patient’s risk of thromboembolism and bleeding. In general, pharmacologic prophylaxis is recommended in patients with high (and possibly moderate) risk of venous thromboembolism who do not have a high risk of bleeding, while mechanical methods are suggested in patients who require thromboprophylaxis but have a high risk of bleeding.

If pharmacologic prophylaxis is indicated in patients undergoing general surgery, ACCP states that an LMWH or low-dose heparin is preferred.

ACCP states that the same recommendations for use of antithrombotic agents in general surgery patients can be applied to patients undergoing bariatric, vascular, and plastic/reconstructive surgery.

Thromboprophylaxis in Cardiac Surgery

Mechanical methods of prophylaxis generally recommended in patients undergoing cardiac surgery; however, ACCP states that low-dose heparin may be considered in cardiac surgery patients with a complicated postoperative course.

Thromboprophylaxis in Neurosurgery

Has been used for prevention of venous thromboembolism in patients undergoing craniotomy; however, benefits may be outweighed by possible increased risk of intracranial hemorrhage. ACCP states that the addition of low-dose heparin to a mechanical method of prophylaxis may be considered in patients at very high risk of thromboembolism (e.g., those undergoing craniotomy for malignant disease) once adequate hemostasis established and risk of bleeding decreases.

Also may be considered as a possible addition to mechanical prophylaxis in high-risk patients undergoing spinal surgery (e.g., those with malignancy or those undergoing surgery with a combined anterior-posterior approach) once adequate hemostasis established and risk of bleeding decreases.

Thromboprophylaxis in Thoracic Surgery

Prevention of postoperative DVT and PE in patients undergoing major thoracic surgery.

Pharmacologic thromboprophylaxis (e.g., low-dose heparin) recommended by ACCP in patients undergoing thoracic surgery who are at high risk of venous thromboembolism, provided risk of bleeding is low.

Thromboprophylaxis in Major Orthopedic Surgery

Has been used for prevention of DVT and PE in patients undergoing total hip-replacement surgery, total knee-replacement surgery, or hip-fracture surgery.

ACCP recommends routine thromboprophylaxis (with a pharmacologic and/or mechanical method) in all patients undergoing major orthopedic surgery because of high risk of postoperative venous thromboembolism; continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery.

Among several antithrombotic agents (e.g., LMWH, fondaparinux, low-dose heparin, warfarin, aspirin) recommended for pharmacologic thromboprophylaxis in patients undergoing major orthopedic surgery, ACCP states LMWHs generally preferred; may consider alternative agents when an LMWH is not available or cannot be used.

When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy and safety of the drugs in addition to other logistics and compliance issues.

Thromboprophylaxis in Selected Medical Conditions

Used for prevention of DVT and PE in acutely ill hospitalized medical patients and in those with medical conditions associated with a high risk of thromboembolism (e.g., cancer).

In general, pharmacologic thromboprophylaxis recommended only in patients considered to be at high risk of venous thromboembolism.

ACCP recommends anticoagulant prophylaxis (e.g., low-dose heparin) in acutely ill, hospitalized medical patients at increased risk of thrombosis who are not actively bleeding and do not have an increased risk of bleeding. Continued thromboprophylaxis suggested for 6–21 days until full mobility is restored or hospital discharge.

Low-dose heparin also suggested by ACCP for pharmacologic thromboprophylaxis in critically ill patients (e.g., those in an intensive care unit [ICU]) who are not actively bleeding and do not have risk factors for bleeding.

Risk of venous thromboembolism is particularly high in patients with cancer. Use of low-dose heparin suggested by ACCP in cancer (solid tumors) outpatients who have additional risk factors for thromboembolism, provided risk of bleeding is low.

Thromboprophylaxis in Trauma

Low-dose heparin may be used for thromboprophylaxis in patients with major trauma. For major trauma patients at high risk of venous thromboembolism, including those with acute spinal cord injury, traumatic brain injury, or spinal surgery for trauma, ACCP suggests the use of both a pharmacologic and mechanical method of prophylaxis, unless contraindications exist.

Thromboembolism During Pregnancy

Has been used for prevention and treatment of venous thromboembolism during pregnancy; however, an LMWH generally is recommended by ACCP because of a more favorable safety profile.

Complications of Pregnancy

Has been used in combination with low-dose aspirin for prevention of recurrent pregnancy loss in women with antiphospholipid antibodies (APLA) syndrome.

Also has been used with aspirin (often combined with immune globulin) for prevention of venous thromboembolism and early pregnancy loss in women who have undergone in vitro fertilization.

Venous Thromboembolism in Pediatric Patients

Has been used for treatment and secondary prevention of venous thromboembolism in neonates and children; venous thromboembolism usually occurs secondary to an identifiable risk factor (e.g., presence of central venous access device) in such patients.

Recommendations regarding use of antithrombotic therapy in children generally based on extrapolation from adult guidelines.

In children with central venous catheters (or umbilical venous catheters) who experience venous thromboembolism, ACCP recommends removal of catheter if no longer functioning or required; at least 3–5 days of therapeutic anticoagulation suggested prior to removal. If such catheters must remain in place, ACCP suggests anticoagulant therapy until catheter is removed.

Cardioversion of Atrial Fibrillation/Flutter

Has been used to reduce the risk of stroke and systemic embolism in patients undergoing electrical or pharmacologic cardioversion for atrial fibrillation or atrial flutter.

Therapeutic anticoagulation with heparin may be used in patients in whom prolonged anticoagulation (e.g., with warfarin for ≥3 weeks) prior to cardioversion is not necessary or not possible; in these situations, heparin or an LMWH generally is administered at the time of transesophageal echocardiograph (TEE) or at presentation (for those with atrial fibrillation ≤48 hours) just prior to cardioversion.

In patients with hemodynamic instability who require urgent cardioversion, ACCP suggests administration of IV heparin or an LMWH prior to cardioversion, if possible; however, such anticoagulant therapy must not delay any emergency intervention.

Thromboembolism Associated with Prosthetic Heart Valves

Used during conversion to maintenance warfarin therapy to reduce the incidence of thromboembolism (e.g., stroke) in patients with prosthetic mechanical heart valves.

ACCP suggests bridging anticoagulation (administration of an LMWH in either prophylactic or therapeutic dosages or IV heparin in prophylactic dosages) during the early postoperative period after insertion of a mechanical heart valve until patient is stable on warfarin therapy.

Also may be used for bridging anticoagulation in patients with a mechanical heart valve in whom therapy with warfarin must be temporarily discontinued (e.g., for major surgery). ACC and AHA state that perioperative use of heparin should be considered for noncardiac surgery, invasive procedures, or dental procedures in patients with prosthetic heart valves who are at high risk for thrombosis without oral antithrombotic therapy (e.g., those with any mechanical mitral valve or a mechanical aortic valve with additional risk factors).

Used for thromboprophylaxis in pregnant women with prosthetic mechanical heart valves. (See Thromboembolism During Pregnancy under Dosage and Administration.)

Renal Vein Thrombosis

Renal vein thrombosis is the most common cause of spontaneous venous thromboembolism in neonates. Although use of anticoagulant therapy in patients with renal vein thrombosis is controversial, heparin is suggested by ACCP as a possible treatment option in selected neonates.

Arterial Thromboembolism

Used to reduce the extent of ischemic injury in patients with acute arterial emboli or thrombosis; however, ACCP states formal studies demonstrating improved outcomes have not been conducted.

In patients with limb ischemia secondary to arterial emboli or thrombosis, immediate systemic anticoagulation with heparin to prevent thrombotic propagation is suggested by ACCP.

Prophylaxis during cardiac catheterization via an artery in neonates and children. If femoral artery thrombosis occurs following cardiac catheterization, therapeutic-dose IV heparin is recommended, followed by subsequent conversion to an LMWH or continued treatment with heparin to complete 5–7 days of therapeutic anticoagulation.

Thromboembolism Associated with Cardiac and Arterial Vascular Surgery

Prevention of activation of the coagulation mechanism during arterial and cardiac surgery.

A nonheparin anticoagulant (e.g., bivalirudin) may be used in place of heparin in patients with acute heparin-induced thrombocytopenia (HIT) or subacute HIT (platelets have recovered, but HIT antibodies still present) who require urgent cardiac surgery. Because HIT antibodies are transient, ACCP states that short-term use of heparin may be appropriate in patients with a remote (>3 months) history of HIT and no detectable antibodies who require cardiac surgery.

Disseminated Intravascular Coagulation

Treatment of acute and chronic consumptive coagulopathies, including disseminated intravascular coagulation.

Thrombosis Associated with Indwelling Venous or Arterial Devices

Maintenance of patency of indwelling peripheral or central venipuncture devices designed for intermittent injections and/or blood sampling.

ACCP suggests use of heparin flushes as an option for primary thromboprophylaxis of central venous access devices in children.

In neonates and children with peripheral arterial catheters, ACCP recommends continuous IV infusion of heparin (in low concentrations) via the catheter for prophylaxis. Also may consider use of heparin for treatment if symptomatic catheter-related thromboembolism occurs.

In neonates with umbilical arterial catheters, ACCP also suggests thromboprophylaxis with low-dose heparin via the catheter to maintain patency.

ST-Segment-Elevation MI (STEMI)

Used in combination with antiplatelet agents (e.g., aspirin) during and after successful coronary artery reperfusion (e.g., thrombolytic agents) for prevention of ischemic complications of STEMI (e.g., death, reinfarction, stroke).

The American College of Cardiology Foundation (ACCF) and AHA state that patients with STEMI undergoing thrombolytic therapy should receive an anticoagulant (e.g., heparin, enoxaparin, fondaparinux) for ≥48 hours, and preferably for the duration of the index hospitalization, up to 8 days or until revascularization is performed. Enoxaparin is preferred over heparin if extended anticoagulation (>48 hours) is necessary.

Acute Ischemic Complications of PCI

Used to reduce the risk of thrombotic complications in patients undergoing PCI. Used in conjunction with aspirin and other standard therapy (e.g., GP IIb/IIIa-receptor inhibitors, P2Y12 receptor antagonists).

Use of a parenteral anticoagulant is recommended in patients undergoing PCI to prevent thrombus formation during the procedure. IV heparin is recommended by AHA, the American College of Cardiology Foundation (ACCF), and the Society for Cardiovascular Angiography and Interventions (SCAI) as an appropriate choice of anticoagulant.

Non-ST-Segment-Elevation Acute Coronary Syndromes (NSTE ACS)

Reduction in the risk of acute cardiac ischemic events (death and/or MI) in patients with NSTE ACS (unstable angina or non-ST-segment-elevation MI [NSTEMI]).

Used concurrently with aspirin and/or other standard therapy (e.g., nitrates, β-adrenergic blocking agents [β-blockers], P2Y12 receptor antagonists).

Initial parenteral anticoagulants with established efficacy in patients with NSTE ACS include enoxaparin, heparin, bivalirudin (only in patients managed with an early invasive strategy), and fondaparinux.

In patients who will undergo CABG, if heparin is already being administered, continue during surgery. If patient is receiving other anticoagulants (enoxaparin, fondaparinux, or bivalirudin), discontinue other anticoagulant and use heparin during CABG.

In patients in whom conservative medical therapy is selected as a postangiographic management strategy, recommendations for continued antiplatelet and anticoagulant therapy generally are based on the presence of CAD.

Treatment of Cerebral Venous Sinus Thrombosis

May be used for treatment of acute cerebral venous sinus (sinovenous) thrombosis in adults. May convert to oral anticoagulant therapy once patient is stabilized.

Recommended by ACCP as an option for initial anticoagulation in children with cerebral venous sinus thrombosis without substantial intracranial hemorrhage. Also has been suggested for use in such children with substantial hemorrhage.

Acute Ischemic Stroke

Heparin anticoagulants (i.e., LMWH or heparin) have been used for thromboprophylaxis in selected patients with acute ischemic stroke; those with additional risk factors for venous thromboembolism are more likely to benefit.

ACCP suggests thromboprophylaxis with an LMWH (in prophylactic dosages), sub-Q heparin, or intermittent pneumatic compression in patients with acute ischemic stroke and restricted mobility; LMWH is preferred over heparin.

Prophylactic-dose heparin usually initiated within 48 hours of onset of stroke and continued throughout hospital stay until patient regains mobility; do not administer within the first 24 hours after thrombolytic therapy.

Also has been used for initial management of acute arterial ischemic stroke in children until dissection and embolic causes have been excluded.

In children with acute arterial ischemic stroke secondary to non-Moyamoya vasculopathy, ACCP recommends ongoing antithrombotic therapy (e.g., heparin) for 3 months.

Heparin may be considered in neonates with a first episode of arterial ischemic stroke associated with a documented cardioembolic source.

Perioperative Management of Antithrombotic Therapy

Used in the perioperative management of patients who require temporary interruption of long-term warfarin therapy for surgery or other invasive procedures.

ACCP suggests perioperative use of an LMWH or IV heparin (bridging anticoagulation) in selected patients with venous thromboembolism, atrial fibrillation, or mechanical prosthetic heart valves depending on their risk of developing thromboembolism without warfarin therapy.

In general, bridging anticoagulation is suggested in such patients who are considered to be at particularly high risk of venous thromboembolism without oral anticoagulant therapy.

Anticoagulant in Blood Transfusions, Blood Samples, and Other Procedures

Used as an in vitro anticoagulant in blood transfusions.

Used for anticoagulation during extracorporeal circulation and dialysis procedures.

• Generic Name: warfarin
• Dosage Forms: n.a.
• Other Brand Names: Coumadin, Jantoven

Treatment and secondary prevention of venous thromboembolism (DVT and/or PE).

Initiate concomitantly with a parenteral anticoagulant (e.g., a low molecular weight heparin [LMWH], heparin [referring throughout this monograph to unfractionated heparin], fondaparinux). Overlap parenteral and oral anticoagulant therapy for ≥5 days and until a stable INR of ≥2 has been maintained for ≥24 hours, then discontinue parenteral anticoagulant.

Anticoagulant therapy generally not recommended for treatment of isolated distal DVT unless symptoms are severe and there is a risk for thrombus extension.

The American College of Chest Physicians (ACCP) recommends a moderate intensity of anticoagulation (target INR 2.5, range 2–3) for most patients with DVT or PE.

Appropriate duration of therapy determined by individual factors (e.g., location of thrombi, presence or absence of precipitating factors, presence of cancer, patient's risk of bleeding). For most cases of venous thromboembolism, a minimum of 3 months of anticoagulant therapy is recommended. Long-term anticoagulation (>3 months) may be considered in selected patients (e.g., those with idiopathic [unprovoked] DVT or PE who are at low risk of bleeding, cancer patients with DVT or PE). (See Dosage under Dosage and Administration.)

Warfarin generally is the preferred anticoagulant for long-term treatment of venous thromboembolism in patients without cancer; however, in patients with cancer, ACCP suggests use of an LMWH over warfarin because of certain factors in such patients that may affect warfarin therapy (e.g., possible reduced response to warfarin, drug interactions, need for invasive procedures that require reversal of anticoagulation).

Used in select pediatric patients with DVT or PE. LMWHs or heparin generally recommended for both initial and ongoing treatment of venous thromboembolism in children; however, warfarin may be indicated in some situations (e.g., recurrent idiopathic venous thromboembolism).

Treatment and secondary prevention of venous thromboembolic events secondary to use of central venous access devices (CVAD) in children. Remove affected CVAD if no longer functioning or required; however, if CVAD required, ACCP suggests giving anticoagulants until catheter is removed. After initial 3 months of therapy, may consider use of prophylactic-dose warfarin (target INR 1.5–1.9); however, therapeutic dosages may be required if recurrent thromboembolism occurs.

Orthopedic Surgery

Prevention of postoperative venous thromboembolism in patients undergoing hip- or knee-replacement surgery or hip-fracture surgery.

ACCP recommends routine thromboprophylaxis (with a pharmacologic and/or mechanical method) in all patients undergoing major orthopedic surgery (hip- or knee-replacement surgery, hip-fracture surgery). Continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery.

Several antithrombotic agents (e.g., LMWHs, fondaparinux, low-dose heparin, warfarin, aspirin) recommended by ACCP for pharmacologic thromboprophylaxis in patients undergoing major orthopedic surgery. Although LMWHs generally preferred, alternative agents (e.g., warfarin) may be considered if an LMWH is not available or cannot be used (e.g., in patients with heparin-induced thrombocytopenia [HIT] or in those who refuse or are uncooperative with sub-Q injections).

When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy, bleeding risk, logistics, and compliance.

Embolism Associated with Atrial Fibrillation

Prevention of stroke and systemic embolism in patients with atrial fibrillation. ACCP, ACC, AHA, the American Stroke Association (ASA), and other experts recommend antithrombotic therapy (e.g., warfarin, aspirin) in all patients with nonvalvular atrial fibrillation (i.e., atrial fibrillation in the absence of rheumatic mitral stenosis, a prosthetic heart valve, or mitral valve repair) who are considered to be at increased risk of stroke, unless such therapy is contraindicated.

Choice of antithrombotic therapy is based on patient's risk for stroke and bleeding. In general, oral anticoagulant therapy (traditionally warfarin) is recommended in patients who have a moderate to high risk for stroke and acceptably low risk of bleeding, while aspirin or no antithrombotic therapy may be considered in patients at low risk of stroke. Patients considered to be at increased risk of stroke generally include those with advanced age (e.g., ≥75 years), history of hypertension, diabetes mellitus, or congestive heart failure. In addition, population-based studies suggest that female sex is an important risk factor for stroke in patients with atrial fibrillation, particularly in patients ≥75 years of age.

AHA and ASA state that oral anticoagulation is not recommended in women ≤65 years of age with atrial fibrillation and no other risk factors; instead, antiplatelet therapy is a reasonable option in selected low-risk women.

In patients with atrial fibrillation at increased risk of stroke who cannot take or choose not to take oral anticoagulants for reasons other than concerns about major bleeding (e.g., those with difficulty maintaining stable INRs, compliance issues, dietary restrictions, cost limitations), combination therapy with clopidogrel and aspirin rather than aspirin alone is recommended.

Antiplatelet agents may be used in combination with warfarin therapy in selected patients who have coexisting conditions that warrant use of antiplatelet therapy (e.g., those with recent placement of an intracoronary stent, those with acute coronary syndrome).

AHA and ASA state that apixaban, dabigatran, or rivaroxaban may be a useful alternative to warfarin for the prevention of stroke and systemic thromboembolism in selected women with paroxysmal or permanent atrial fibrillation and certain risk factors who do not have a prosthetic heart valve or hemodynamically important valve disease, severe renal failure (creatinine clearance <15 mL/minute), lower body weight (<50 kg), or advanced liver disease (impaired baseline clotting function). Warfarin generally should remain the treatment of choice in patients with severe renal impairment pending clinical outcomes data with the non-vitamin K antagonist oral anticoagulants in such patients.

Experts suggest managing antithrombotic therapy in patients with atrial flutter in the same manner as in patients with atrial fibrillation.

Cardioversion of Atrial Fibrillation

Prevention of embolization in patients undergoing pharmacologic or electrical cardioversion of atrial fibrillation.

ACCP and other experts recommend that patients with atrial fibrillation lasting >48 hours or of unknown duration who are to undergo elective cardioversion receive therapeutic anticoagulation (e.g., usually with warfarin) for ≥3 weeks prior to cardioversion; alternatively, a transesophageal echocardiography (TEE)-guided approach may be used. After successful cardioversion, all patients should receive therapeutic anticoagulation for ≥4 weeks.

Experts suggest the same approach to thromboprophylaxis in patients undergoing cardioversion for atrial flutter as that used in patients with atrial fibrillation.

Embolism Associated with Valvular Heart Disease

Prevention of thromboembolism associated with various types of valvular heart disease, in combination with or as an alternative to low-dose aspirin; assess risk of thromboembolism versus risk of bleeding when determining choice of antithrombotic therapy.

Warfarin anticoagulation (INR 2–3) is recommended in patients with rheumatic mitral valve disease and concurrent atrial fibrillation, left atrial thrombus, or a history of systemic embolism.

ACCP suggests warfarin anticoagulation in patients with rheumatic mitral valve disease and normal sinus rhythm who have a left atrial diameter >5.5 cm because of their high risk of developing atrial fibrillation.

Warfarin also recommended by ACC and AHA for prevention of thromboembolic events in selected patients with mitral valve prolapse and a history of stroke who have concomitant atrial fibrillation, mitral valve regurgitation, or left atrial thrombus.

Generally should not initiate antithrombotic therapy in patients with infective endocarditis involving a native valve because of the risk of serious (e.g., intracerebral) hemorrhage and lack of documented efficacy. In patients with a prosthetic valve who are already receiving warfarin, ACCP suggests temporary discontinuance of the drug if infective endocarditis develops and reinitiation of therapy once invasive procedures no longer required and patient is stabilized without signs of neurologic complications.

Used in a limited number of patients undergoing percutaneous balloon mitral valvotomy to prevent left atrial embolism.

Thromboembolism Associated with Prosthetic Heart Valves

Used to reduce the incidence of thromboembolism (e.g., stroke) in patients with prosthetic mechanical or biological heart valves.

Risk of systemic embolism higher with mechanical versus bioprosthetic valves, higher with first-generation mechanical (e.g., caged ball, caged disk) valves versus newer mechanical (e.g., bileaflet, Medtronic Hall tilting disk) valves, higher with >1 prosthetic valve, and higher with prosthetic mitral versus aortic valves; risk also increases in the presence of atrial fibrillation.

Long-term warfarin therapy required in all patients with mechanical heart valves because of associated high risk of thromboembolism.

Warfarin anticoagulation also suggested in patients with mitral bioprosthetic valves, at least for the first 3 months after valve insertion. In patients with aortic bioprosthetic valves who are in sinus rhythm and have no other indications for warfarin therapy, aspirin generally suggested for initial (e.g., first 3 months after valve insertion) and long-term antithrombotic therapy. However, long-term warfarin therapy (INR 2.5, range 2–3) may be indicated in some patients with bioprosthetic heart valves who have additional risk factors for thromboembolism (e.g., atrial fibrillation, prior thromboembolism, left ventricular dysfunction, hypercoagulable states).

In general, target INR of 2.5 (range 2–3) is suggested in patients with an aortic mechanical valve, while target INR of 3 (range 2.5–3.5) is recommended in those with a mitral mechanical valve. A higher intensity of warfarin anticoagulation also may be considered in patients with both aortic and mitral mechanical valves.

ACCP recommends adding low-dose aspirin (e.g., 50–100 mg daily) to warfarin therapy in all patients with mechanical heart valves who are at low risk of bleeding. Combination therapy also may be warranted in some patients with bioprosthetic valves (e.g., those with additional risk factors for thrombosis).

ST-Segment-Elevation MI (STEMI)

Used for secondary prevention to reduce the risk of death, recurrent MI, and thromboembolic events such as stroke or systemic embolization after acute STEMI.

In general, antiplatelet therapy is preferred to anticoagulants for secondary prevention and risk reduction in patients with atherosclerosis, including those with acute STEMI; however, warfarin (in combination with low-dose aspirin) may be indicated in selected patients (e.g., those with atrial fibrillation, prosthetic heart valve, left ventricular thrombus, or concomitant venous thromboembolic disease).

The manufacturer and other experts recommend warfarin therapy (target INR 2–3) in conjunction with low-dose aspirin (≤100 mg daily) for ≥3 months following acute STEMI in high-risk patients (e.g., those with large anterior MI, substantial heart failure, intracardiac thrombus visible on transthoracic echocardiography, atrial fibrillation, history of previous thromboembolic event). Triple therapy with warfarin, low-dose aspirin, and clopidogrel is suggested in some patients (e.g., those with anterior MI and left ventricular thrombus who undergo coronary artery stent placement).

Cerebral Embolism

Oral anticoagulation with warfarin or one of the non-vitamin K antagonist oral anticoagulants (e.g., apixaban, dabigatran, rivaroxaban) is recommended for secondary prevention of cerebral embolism in patients with TIAs or ischemic stroke and concurrent atrial fibrillation, provided no contraindications exist.

Warfarin anticoagulation also is recommended for the prevention of recurrent stroke in patients at high risk for recurring cerebral embolism from other cardiac sources (e.g., prosthetic mechanical heart valves, anterior MI and left ventricular thrombus).

Antiplatelet agents generally preferred over oral anticoagulation for secondary prevention of noncardioembolic stroke in patients with a history of ischemic stroke or TIA.

ACCP, AHA, and ASA generally recommend oral anticoagulation with warfarin following initial therapy with heparin or an LMWH in patients with acute cerebral venous sinus thrombosis. AHA and ASA recommend postpartum anticoagulation with warfarin (target INR of 2–3) as an alternative to LMWH for at least 6 weeks (for a total minimum duration of 6 months of anticoagulant therapy) following LMWH therapy during pregnancy in women with cerebral venous sinus thrombosis. Warfarin is suggested by ACCP as an option for long-term anticoagulation in children with arterial ischemic stroke associated with dissection or a cardioembolic cause. Warfarin also has been used in children with cerebral venous sinus thrombosis who do not have substantial intracranial hemorrhage.

Arterial Occlusive Disease

Has been used in certain patients with peripheral arterial occlusive disease. However, ACCP generally recommends use of antiplatelet agents (aspirin or clopidogrel) for primary or secondary prevention of cardiovascular events in patients with peripheral arterial disease.

Indefinite anticoagulation with warfarin recommended by ACCP in all patients with chronic thromboembolic pulmonary hypertension.

Heparin-Induced Thrombocytopenia

May be used as follow-up therapy after initial treatment with a nonheparin anticoagulant (e.g., lepirudin, argatroban) in patients with HIT. Overlap therapy with warfarin and nonheparin anticoagulant for ≥5 days and until desired INR has been achieved.

Do not initiate warfarin in patients with HIT until substantial platelet recovery occurs (e.g., platelet count ≥150,000/mm3); in patients already receiving warfarin at the time of HIT diagnosis, ACCP suggests administration of vitamin K. (See Necrosis under Cautions.)