Is tafamidis (Vyndaqel) used in wild-type cardiac amyloidosis?

Tafamidis Use in Wild-Type Cardiac Amyloidosis

Yes, tafamidis is indicated for the treatment of wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) to reduce cardiovascular mortality and cardiovascular-related hospitalization. 1

Indications and Evidence

• Tafamidis is FDA-approved for the treatment of cardiomyopathy of wild-type or hereditary (variant) transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization 1
• The 2022 AHA/ACC/HFSA guidelines provide a Class 1 (strong) recommendation with Level B-R evidence for tafamidis use in patients with wild-type or variant transthyretin cardiac amyloidosis with NYHA class I to III heart failure symptoms 2
• Tafamidis is currently the only therapy proven to improve cardiovascular outcomes in ATTR-CM, including the wild-type form 2

Dosing and Administration

• Tafamidis is available in two formulations 2:
  • Tafamidis meglumine (Vyndaqel): 80 mg (four 20-mg capsules) once daily
  • Tafamidis (Vyndamax): 61 mg (one capsule) once daily
• The two formulations are not substitutable on a per mg basis 1
• Capsules should be swallowed whole and not crushed or cut 1

Efficacy in Wild-Type ATTR-CM

• In the ATTR-ACT trial, tafamidis demonstrated lower all-cause mortality (29.5% versus 42.9%) and lower cardiovascular-related hospitalization (0.48 versus 0.70 per year) after 30 months compared to placebo 2
• Real-world data supports that tafamidis use is associated with reduced heart failure exacerbations and all-cause mortality in patients with wild-type TTR amyloidosis and heart failure 3
• Tafamidis appears to slow down cardiac disease progression in ATTRwt-CM patients based on cardiovascular magnetic resonance imaging parameters after one year of therapy 4
• Early experience in Japanese patients with ATTRwt-CM showed tafamidis to be safe with maintenance of disease severity in the short term 5

Patient Selection Considerations

• Greatest benefit is observed when administered early in the disease course 2
• The survival benefit becomes apparent after approximately 18 months of treatment 2
• Benefit has not been observed in patients with 2:
  • NYHA class IV symptoms
  • Severe aortic stenosis
  • Impaired renal function (eGFR <25 mL/min/1.73 m²)
• Patients with NYHA class III symptoms may experience higher rates of cardiovascular-related hospitalizations, potentially due to longer survival during a more severe period of disease 2

Cost Considerations

• At 2020 list prices, tafamidis provided low economic value (>$180,000 per QALY gained) 2
• The cost would need to decrease by approximately 80% to be considered intermediate value 2
• For patients with affordability issues, some clinicians may consider the 20-mg dose, as there is evidence of benefit, though this is not FDA-approved 2

Management Algorithm for ATTR-CM

1. Confirm diagnosis of ATTR-CM through appropriate testing 2
2. Perform TTR gene sequencing to differentiate between wild-type (ATTRwt) and variant (ATTRv) forms 2
3. For ATTRwt-CM with NYHA class I-III symptoms, initiate tafamidis therapy 2
4. For patients with atrial fibrillation and cardiac amyloidosis, anticoagulation is reasonable regardless of CHA₂DS₂-VASc score (Class 2a recommendation) 2
5. Standard heart failure medications may be poorly tolerated in ATTR-CM patients 2:
   • ARNi, ACEi, and ARB may exacerbate hypotension due to amyloid-associated autonomic dysfunction
   • Beta blockers may worsen symptoms as patients rely on heart rate response to maintain cardiac function

Monitoring

• Regular follow-up to assess:
  • NT-proBNP and troponin levels 2
  • Echocardiography including strain measurements 2
  • Electrocardiogram and Holter monitoring 2
  • NYHA functional class 2

In summary, tafamidis is a first-line therapy for wild-type transthyretin cardiac amyloidosis with demonstrated mortality and hospitalization benefits, though cost remains a significant barrier to treatment.