What are the treatment options for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

Treatment of cardiac amyloidosis should be based on the specific amyloid subtype, with tafamidis as first-line therapy for ATTR cardiomyopathy and daratumumab-based regimens for AL amyloidosis. 1, 2

Diagnosis and Classification

Before initiating treatment, accurate typing of cardiac amyloidosis is essential:

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

Treatment of ATTR Cardiac Amyloidosis

First-Line Therapy

• Tafamidis (Vyndaqel/Vyndamax): FDA-approved TTR stabilizer that reduces all-cause mortality (29.5% vs 42.9%) and cardiovascular-related hospitalizations (0.48 vs 0.70 per year) 2, 3
  • Dosing: Either tafamidis meglumine 80 mg (4 × 20 mg capsules) or tafamidis 61 mg (1 capsule) once daily
  • Take capsules whole; do not crush or cut 3

Alternative Options

• Diflunisal: Non-FDA approved TTR stabilizer that slows disease progression by binding to TTR tetramer 2
• Acoramidis (Attruby): Novel TTR stabilizer that reduced all-cause mortality by up to 42% and cardiovascular hospitalizations by ~50% 2

TTR Silencers (for ATTRv with polyneuropathy)

• Patisiran: Requires premedication and vitamin A supplementation
• Inotersen: Requires monitoring for thrombocytopenia and glomerulonephritis
• Vutrisiran: Less frequent dosing schedule than other silencers 2

Treatment of AL Cardiac Amyloidosis

First-Line Therapy

• Daratumumab + CyBorD (cyclophosphamide, bortezomib, dexamethasone): Standard of care for newly diagnosed AL amyloidosis, with very good partial responses or better in 78.5% of patients 1
  • Only FDA-approved therapy for AL amyloidosis

For Eligible Patients

• High-dose melphalan + autologous stem cell transplantation (HDM/SCT):
  • For highly selected patients with less advanced cardiac involvement
  • Offers possibility of long-lasting remission with very good partial hematological response in about 70% of patients
  • Median survival >15 years in patients achieving complete response 1
  • Generally, EF <40% is considered a contraindication to SCT 1

For Patients Not Eligible for SCT

• Bortezomib-based regimens in combination with dexamethasone and an alkylating agent:
  • CyBorD (cyclophosphamide, bortezomib, dexamethasone)
  • Bortezomib-melphalan-dexamethasone 1
• Single-agent daratumumab with minimal dexamethasone for patients with advanced cardiac involvement (NT-proBNP >8,500 pg/mL) 1

Symptomatic Management

Heart Failure Management

• Diuretics: Mainstay of supportive treatment for cardiac failure 1, 4
• Careful fluid management: Monitor for volume depletion

Arrhythmia Management

• Anticoagulation: Recommended for atrial fibrillation regardless of CHA₂DS₂-VASc score 2
• Low-dose beta-blockers or amiodarone: For management of dysrhythmias 5

Orthostatic Hypotension

• Increased fluid intake, salt tablets, fludrocortisone, midodrine, droxidopa, or pyridostigmine 2

Advanced Therapies for End-Stage Disease

• Heart transplantation: For selected patients with end-stage disease 2
• Combined heart-liver transplantation: For hereditary ATTR, as liver transplantation cures the disease process 2
• Heart transplantation followed by bone marrow transplantation: In selected AL amyloidosis patients 2

Monitoring and Follow-up

• Regular monitoring of disease progression every 6-12 months:
  • Neurological function assessment
  • Cardiac status evaluation
  • Response to therapy 2

Important Considerations

• Early treatment is critical for better outcomes in terms of neuropathy impairment and quality of life 2
• Treatment should be coordinated through a multidisciplinary team including cardiology, hematology, neurology, and other specialties as needed 1
• Economic considerations: Tafamidis has low economic value at current list prices (>$180,000 per QALY gained) 2

The treatment landscape for cardiac amyloidosis has evolved dramatically, with disease-modifying therapies now available for both major types, offering significant improvements in survival and quality of life when initiated early in the disease course.