Cardiac Amyloidosis Medication

Updated: May 09, 2019
  • Author: Gyanendra K Sharma, MD, FACC, FASE; Chief Editor: Terrence X O'Brien, MD, MS, FACC  more...
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Medication

Medication Summary

The goals of pharmacotherapy include symptom relief, improved cardiac output, shortened hospital stay, fewer emergency department visits, and decreased mortality.

Tafamidis meglumine (Vyndaqel) and tafamidis (Vyndamax) are the first drugs approved by the FDA for cardiomyopathy caused by transthyretin-mediated amyloidosis (ATTR-CM) in adults. [72, 73]  

Because of their negative inotropic effects, rate-limiting calcium channel blocking agents (ie, verapamil, diltiazem) are contraindicated, as they can precipitate congestive heart failure.

Melphalan and prednisone have been used with limited benefit in cardiac amyloidosis. Better results may be obtained with the combination of melphalan and dexamethasone. Cyclophosphamide and thalidomide have also been used as an alternative therapy. Colchicine has also been used sometimes. Autologous stem cell transplantation and high-dose chemotherapy have shown promise in patients with limited cardiac involvement, with increased survival and better quality of life.

In a study that used a combination of cyclophosphamide/bortezomib/dexamethasone (CyBorD) to treat 230 patients with light chain (AL) amyloidosis, investigators found that the overall hematologic response rate was 60%. [74] Of the 201 patients with measurable disease, the overall hematologic response rate was 62%, with 43% achieving at least very good partial response (VGPR). [74]  In another study, use of triple therapy (bortezomib, dexamethasone, and an alkylating agent) in the treatment of patients with AL who presented with symptomatic heart failure resulted in improved survival after adjustment of clinical variables. [75]

Cardiac transplantation is not a good choice in patients with cardiac involvement because of increased mortality. [76, 77, 78, 79, 80, 81, 82]  A 2016 Mayo Clinic study showed a median overall survival of 3.5 years in 23 patients (median age, 53 years) with AL who received orthotopic heart transplantation. [83] Seven patients who achieved a complete hematologic response to either chemotherapy or autologous stem cell transplantation had a median survival of 10.8 years. [83]

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Diuretics, Loop

Class Summary

These agents relieve peripheral and pulmonary congestion. They promote excretion of water and electrolytes by the kidneys and are used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention has resulted in edema or ascites.

Furosemide (Lasix)

Furosemide increases excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. The bioavailability of oral furosemide is 50%. If a switch is made from IV to oral administration, an equivalent oral dose should be used. Doses vary depending on the patient's clinical condition.

Patients with evidence of heart failure require diuretic therapy. As these patients are preload dependent, such a therapy should be judiciously used to avoid hypotension and depletion of intravascular volume.

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Inotropic Agents

Class Summary

Inotropic agents are reserved for patients who need hemodynamic-directed treatment during acute decompensation, those refractory to maximal standard therapy, as palliation for end-stage heart failure, or as a bridge to transplantation for appropriate candidates.

Digoxin (Lanoxin)

Digoxin is a cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system. It acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.

Digoxin binds to amyloid fibrils and predisposes these patients to digoxin toxicity. [62] A low dose of digoxin should be used when indicated, as toxicity can occur even when serum digoxin level is in the therapeutic range. No precise dose recommendation can be made due to lack of evidence. Patients receiving digoxin should be closely monitored for electrocardiographic evidence of digoxin toxicity (eg, heart block, ventricular arrhythmia, junctional rhythm).

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Antidysrhythmics, III

Class Summary

Antiarrhythmics are useful in patients with supraventricular and nonsustained ventricular tachycardias. Not all antiarrhythmics are considered safe in patients with structural heart disease.

Amiodarone (Cordarone)

Amiodarone may inhibit atrioventricular conduction and sinus node function. It prolongs the action potential and refractory period in myocardium and inhibits adrenergic stimulation. Amiodarone may improve mortality rates in patients with cardiomyopathy.

It is better tolerated and should be used in patients with atrial fibrillation. Amiodarone can be used intravenously (150 mg IV bolus; then 1 mg/minute for 6 hrs followed by 0.5 mg/minute for 18 hrs or by mouth 400 mg 3 times daily for 7 days followed by 400 mg twice daily for 1 week as a loading dose. The usual maintenance dose is 200-400 mg daily. The patients should be closely followed for amiodarone toxicity, including QT prolongation, hepatic, and thyroid function abnormalities. Dose of warfarin should be reduced, and digoxin should not be administered concurrently with amiodarone in patients with amyloidosis.

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Anticoagulants, Cardiovascular

Class Summary

The use of anticoagulants is restricted to patients in atrial fibrillation, with artificial valves, and with known mural thrombus. Some data support their use in patients with low ejection fractions.

Warfarin (Coumadin)

Warfarin interferes with the hepatic synthesis of vitamin K–dependent coagulation factors. Anticoagulation therapy is indicated in patients with atrial fibrillation or documented cardiac thrombi. It is also indicated in advanced amyloidosis with the loss of atrial function when thrombi can form even in presence of a sinus rhythm. [63] Usual starting dose of warfarin is 2.5-5 mg daily depending upon the age of the patient and comorbid conditions

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Alpha-Adrenergic Agonists

Class Summary

These agents may reduce sympathetic outflow, which may reduce muscle tone.

Midodrine

Midodrine is a prodrug with activity as an alpha1-adrenoreceptor agonist. This agent is widely used to treat orthostatic hypotension. Midodrine acts directly on the vasculature to increase BP and avoids electrolyte abnormalities associated with fludrocortisone. Fludrocortisone should be avoided because of risk of salt and water retention. Midodrine has often caused an unpleasant sensation in the scalp (due to piloerection).

Usual recommended dose of Midodrine is 10 mg by mouth 3 times daily.

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Transthyretin Binders

Class Summary

Accumulation of amyloid fibrils composed of misfolded transthyretin protein in the heart leads to transthyretin amyloid cardiomyopathy and heart failure. Drugs that stabilize the amyloidogenic process may slow disease progression.

Tafamidis (Vyndamax)

Tafamidis is indicated for cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. Tafamidis is a selective stabilizer of TTR. Tafamidis binds to TTR at thyroxine binding sites, stabilizing the tetramer and slowing dissociation into monomers, the rate-limiting step in the amyloidogenic process. NOTE: Tafamidis and tafamidis meglumine are not interchangeable on a mg-per-mg basis.

Tafamidis meglumine (Vyndaqel)

Tafamidis meglumine is indicated for cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. Tafamidis is a selective stabilizer of TTR. Tafamidis binds to TTR at thyroxine binding sites, stabilizing the tetramer and slowing dissociation into monomers, the rate-limiting step in the amyloidogenic process. NOTE: Tafamidis and tafamidis meglumine are not interchangeable on a mg-per-mg basis.

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