What is the treatment for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

The treatment of cardiac amyloidosis should be tailored to the specific type of amyloidosis, with tafamidis being the first-line therapy for transthyretin amyloidosis cardiomyopathy (ATTR-CM) to reduce cardiovascular mortality and hospitalizations. 1, 2

Determining Amyloid Type

Accurate typing of cardiac amyloidosis is essential before initiating treatment:

• ATTR amyloidosis: Diagnosed using bone scintigraphy in patients without evidence of monoclonal light chains
• AL amyloidosis: Requires serum free light chain assay, serum and urine immunofixation electrophoresis
• Genetic testing to differentiate hereditary variant (ATTRv) from wild-type (ATTRwt) 1

Treatment Approach by Amyloid Type

Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM)

1. First-line therapy: Tafamidis

   • FDA-approved for both wild-type and hereditary ATTR-CM
   • Dosage: VYNDAQEL 80 mg (four 20-mg capsules) or VYNDAMAX 61 mg (one capsule) orally once daily
   • Reduces cardiovascular mortality and hospitalizations 1, 2
   • Demonstrated 29.5% vs 42.9% reduction in all-cause mortality and reduced cardiovascular-related hospitalizations (0.48 vs 0.70 per year) 1

2. Alternative options (if tafamidis is not available):

   • Diflunisal: Non-FDA approved TTR stabilizer that slows disease progression
   • Acoramidis (Attruby): Novel TTR stabilizer that reduced all-cause mortality by up to 42% and cardiovascular hospitalizations by ~50% 1

3. For ATTRv with polyneuropathy:

   • TTR silencers (patisiran, inotersen, or vutrisiran)
   • Requires vitamin A supplementation due to reduced TTR-mediated vitamin A transport
   • Monitoring requirements for inotersen: weekly platelet counts and biweekly serum creatinine and urine protein-creatinine ratio 1

Light Chain (AL) Amyloidosis

• Proteasome inhibitor-based chemotherapy with daratumumab
• When feasible, autologous stem cell transplantation 3

Symptomatic Management

• Heart failure: Diuretics are the mainstay of supportive treatment 1, 4
• Atrial fibrillation: Anticoagulation recommended regardless of CHA₂DS₂-VASc score 1
• Neuropathic pain: Pregabalin, gabapentin, or duloxetine 1
• Orthostatic hypotension: Increased fluid intake, salt tablets, fludrocortisone, midodrine, droxidopa, or pyridostigmine 1

Advanced Therapies for End-Stage Disease

• Heart transplantation for end-stage disease in selected patients
• Combined heart-liver transplantation for hereditary ATTR
• Heart transplantation followed by bone marrow transplantation in selected AL amyloidosis patients 1, 3

Monitoring and Follow-up

• Regular monitoring of disease progression every 6-12 months
• Assess neurological function and cardiac status 1
• Monitor for BCRP substrate-related toxicities when tafamidis is co-administered with drugs that are BCRP substrates (e.g., methotrexate, rosuvastatin, imatinib) 2

Important Considerations and Pitfalls

• Early treatment is critical for better outcomes in terms of neuropathy impairment and quality of life 1
• Avoid calcium channel blockers and digoxin as they may bind to amyloid fibrils and cause toxicity
• Use beta-blockers cautiously and at low doses for dysrhythmia management 4
• Economic considerations: Tafamidis has low economic value at 2020 list prices (>$180,000 per QALY gained) 1
• Pregnancy: Tafamidis may cause fetal harm when administered to pregnant women based on animal studies 2

Early diagnosis and prompt initiation of appropriate therapy are essential for improving outcomes in cardiac amyloidosis, which traditionally has had a poor prognosis 3, 4.