What are the best treatments for cardiac amyloidosis?

Best Treatments for Cardiac Amyloidosis

The best treatment for cardiac amyloidosis depends on the type, with daratumumab-CyBorD being the standard of care for newly diagnosed AL amyloidosis, while tafamidis is the first-line treatment for ATTR cardiac amyloidosis. 1, 2, 3

Light Chain (AL) Cardiac Amyloidosis Treatment

First-Line Treatment

• Daratumumab-CyBorD (daratumumab plus cyclophosphamide, bortezomib, and dexamethasone) is now the standard of care for newly diagnosed AL amyloidosis 1
  • Produces unprecedented high rates of deep hematologic responses (78.5% vs 49.2% with CyBorD alone)
  • Currently the only FDA-approved treatment specifically for AL amyloidosis

For Transplant-Eligible Patients

• Autologous stem cell transplantation (SCT) may be considered for selected patients 1
  • Eligibility criteria:
    • EF >40% (EF ≤40% is a contraindication)
    • Absence of advanced cardiac involvement
    • Only about 25% of newly diagnosed patients are eligible
  • Daratumumab-CyBorD may be used as induction therapy before SCT

For Transplant-Ineligible Patients

• Alternative regimens for patients who cannot tolerate daratumumab-CyBorD:
  • CyBorD alone (cyclophosphamide, bortezomib, dexamethasone) 1
  • Bortezomib-melphalan-dexamethasone 1
  • For patients with very advanced cardiac involvement (NT-proBNP >8,500 pg/mL): single-agent daratumumab with minimal dexamethasone 1

Cardiac Transplantation

• Generally not recommended for AL amyloidosis due to high risk of recurrence in the transplanted heart 1
• May be considered in very selected patients when followed by bone marrow transplantation (5-year survival rate of 35-55%) 1

Transthyretin (ATTR) Cardiac Amyloidosis Treatment

FDA-Approved Therapies

• Tafamidis (Vyndaqel/Vyndamax): First-line treatment 2, 3
  • Significantly reduces all-cause mortality (29.5% vs 42.9%) and cardiovascular-related hospitalization
  • Stabilizes TTR tetramer, preventing dissociation into amyloidogenic monomers
  • Available in two formulations: 20 mg (Vyndaqel) and 61 mg (Vyndamax)

Other TTR Stabilizers

• Diflunisal: Non-steroidal anti-inflammatory drug that stabilizes TTR 2
  • Not FDA-approved for this indication but has shown effectiveness in slowing disease progression
• Acoramidis (Attruby): Recently FDA-approved TTR stabilizer 2
  • Near-complete TTR stabilizer (~96%)
  • Reduced all-cause mortality by up to 42%

TTR Silencers (Gene Therapy)

• Patisiran: Small interfering RNA that reduces TTR production 2
  • Dosing: 0.3 mg/kg IV every 3 weeks (maximum 30 mg)
• Inotersen: Antisense oligonucleotide that reduces TTR production 2
  • Dosing: 284 mg SC once weekly
  • Requires vitamin A supplementation and monitoring for thrombocytopenia and glomerulonephritis
• Vutrisiran: Small interfering RNA similar to patisiran 2
  • Dosing: 25 mg SC every 3 months
  • Requires vitamin A supplementation

Transplantation Options

• Combined cardiac and liver transplantation for hereditary ATTR amyloidosis 1, 2
  • 5-year survival rate of 50-80% in selected patients
  • Liver transplantation cures the amyloidosis process as TTR protein is synthesized in the liver

Supportive Treatment for All Types of Cardiac Amyloidosis

Heart Failure Management

• Diuretics: Mainstay therapy for fluid overload 1
  • Use with caution to avoid hypotension and volume contraction

Medications to Use with Caution or Avoid

• Beta-blockers: May be useful to increase diastolic filling time and control heart rate in atrial fibrillation, but use with caution 1
• Calcium channel blockers: Should be avoided as they bind to amyloid fibrils causing exaggerated hypotension 1
• Digoxin: Should be avoided as it binds to amyloid fibrils, predisposing to toxicity even with normal serum levels 1

Anticoagulation

• Warfarin or direct thrombin inhibitors are indicated for patients with: 1
  • Atrial fibrillation
  • History of embolic stroke/transient ischemic attack
  • Consider in patients with sinus rhythm who have evidence of atrial mechanical dysfunction

Monitoring Treatment Response

AL Amyloidosis

• Hematologic response: Monitor serum free light chains 1
• Organ response: Assess NT-proBNP, troponin, echocardiography 1

ATTR Amyloidosis

• Regular assessment of cardiac function and symptoms
• Monitor for side effects of specific therapies

Important Considerations

• Early diagnosis and treatment are crucial for better outcomes 2
• Treatment should be initiated promptly once diagnosis is confirmed
• Cardiac amyloidosis management requires collaboration between cardiologists, hematologists, and other specialists 2
• Patients with AL amyloidosis receiving plasma cell-directed therapies need careful monitoring for cardiac decompensation, including heart failure, arrhythmias, and thromboembolism 1

Remember that treatment outcomes are significantly better when cardiac amyloidosis is diagnosed and treated early, before extensive amyloid deposition has occurred.