Dabigatran Etexilate Mesylate and Dronedarone Hydrochloride

• Generic Name: dabigatran
• Dosage Forms: n.a.
• Other Brand Names: Pradaxa

Reduction in risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Some evidence suggests that dabigatran 150 mg twice daily may produce similar or superior outcomes in such patients compared with warfarin.

The American College of Chest Physicians (ACCP), American Stroke Association (ASA), ACC, AHA, and other experts currently recommend that antithrombotic therapy be given to 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 contraindicated.

Antithrombotic therapy in patients with atrial flutter generally managed in the same manner as in patients with atrial fibrillation.

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 at moderate to high risk of 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 prior ischemic stroke or TIA, advanced age (e.g., ≥75 years), history of hypertension, diabetes mellitus, or CHF. In addition, female sex is considered an important risk factor for stroke in patients with atrial fibrillation, particularly in patients ≥75 years of age.

ACCP and other experts suggest the use of dabigatran as an alternative to warfarin in selected patients with atrial fibrillation at increased risk of stroke (e.g., warfarin-naive patients, those with difficulty maintaining therapeutic INRs with warfarin, those taking multiple drugs that may interact with warfarin). Warfarin may continue to be preferred in certain patients such as those with severe renal insufficiency or liver disease, a history of dyspepsia or GI ulcer, hemodynamically important valvular heart disease or a prosthetic heart valve, and in those already achieving excellent anticoagulation control with warfarin (e.g., INR in therapeutic range >70% of the time).

Relative efficacy and safety of dabigatran and other non-vitamin K antagonist oral anticoagulants (e.g., apixaban, rivaroxaban) remains to be fully elucidated.

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 (Clcr <15 mL/minute), lower body weight (<50 kg), or advanced liver disease (impaired baseline clotting function).

When selecting an appropriate anticoagulant, consider individual patient's risks of stroke and bleeding; patient compliance, preference, and comorbidities; cost; availability of agents to reverse anticoagulant effects in case of bleeding complications; availability of facilities to monitor INR; and degree of current INR control in patients already taking warfarin.

Do not use in patients with prosthetic mechanical heart valves; increased risk of serious thromboembolic and bleeding events observed in such patients receiving dabigatran compared with warfarin therapy.

Efficacy and safety not evaluated in patients with other forms of valvular heart disease, including those with bioprosthetic heart valves; use not recommended in such patients.

Treatment and Secondary Prevention of DVT and/or PE

Treatment and secondary prevention of acute DVT and/or PE following initial treatment with a parenteral anticoagulant for 5–10 days.

Also used as extended therapy to reduce the risk of recurrent DVT and PE in patients treated previously for the acute thromboembolic event.

Recommended by ACCP as an acceptable option for long-term anticoagulation in patients with proximal DVT and/or PE after initial treatment with a parenteral anticoagulant; however, pending additional data with dabigatran, ACCP suggests use of warfarin or LMWH over dabigatran in such patients.

Cardioversion of Atrial Fibrillation/Flutter

Has been used for prevention of stroke and systemic embolism in patients undergoing pharmacologic or electric cardioversion for atrial fibrillation/flutter.

Although warfarin is traditionally used, dabigatran is recommended by ACCP as an acceptable choice of anticoagulant for precardioversion anticoagulation in patients with atrial fibrillation lasting >48 hours or of unknown duration; prolonged precardioversion anticoagulation generally is not required in patients with atrial fibrillation of short duration (e.g., ≤48 hours).

Thromboprophylaxis in Major Orthopedic Surgery

Prevention of postoperative DVT and PE in patients undergoing hip-replacement surgery.

As effective as enoxaparin in reducing the risk of venous thromboembolism in patients undergoing elective total hip-replacement surgery with similar rates of bleeding.

Has been used for prevention of thromboembolism in patients undergoing total knee-replacement surgery.

ACCP considers dabigatran an acceptable option for pharmacologic thromboprophylaxis in patients undergoing total hip- or knee-replacement surgery; however, a low molecular weight heparin (LMWH) generally is preferred. Dabigatran may be a reasonable choice when an LMWH is not available or cannot be used.

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

Cerebral Embolism

Has been used for secondary prevention of cardioembolic stroke in patients with TIAs or ischemic stroke and concurrent atrial fibrillation. ACCP suggests use of dabigatran (150 mg twice daily) over warfarin in such patients.

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

• Generic Name: dronedarone
• Dosage Forms: n.a.
• Other Brand Names: Multaq

Reduction of risk of hospitalization for atrial fibrillation in patients in sinus rhythm who have a history of paroxysmal or persistent atrial fibrillation.

Do not use in patients with permanent atrial fibrillation (i.e., patients in whom normal sinus rhythm will not or cannot be restored); increased risk of cardiovascular events and death in such patients. (See Warnings.)

Less effective than amiodarone in preventing recurrence of atrial fibrillation but appears to have an improved safety profile (based on short-term data). Long-term data and experience needed to elucidate relative safety and tolerability of dronedarone versus amiodarone because of some late-onset adverse effects of amiodarone (e.g., pulmonary toxicity).

Efficacy of retreatment with dronedarone in patients who relapse after initial successful treatment or in those who fail therapy with amiodarone not established.

Individualize treatment of atrial fibrillation/flutter based on relative benefits and risks of various therapies (e.g., rhythm versus rate control, nondrug therapies such as ablation and pacemaker implantation), patient age, and patient preference and tolerance of the arrhythmia.