Tafamidis For Transthyretin Cardiac Amyloidosis in Older Adults With Associated Geriatric Conditions

Quick Takes

  • Tafamidis, a transthyretin stabilizer, is currently the standard of care for patients diagnosed with transthyretin amyloidosis (ATTR).
  • Taking a comprehensive approach to the care of older adults with ATTR is important.
  • A shared decision-making process for the use of tafamidis should account for geriatric conditions that include social and financial implications.

Tafamidis, a transthyretin stabilizer, inhibits dissociation of the tetrameric transthyretin protein into monomers, which is the rate-limiting step in amyloidogenesis. Tafamidis was shown in the ATTR-ACT (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial) data to significantly reduce morbidity and mortality in older adults with transthyretin cardiac amyloidosis (ATTR-CA).1

Tafamidis is more effective earlier in the course of the disease before significant end-organ dysfunction occurs.2 In the ATTR-ACT, participants with New York Heart Association (NYHA) class III heart failure (HF) survived longer but had an increased risk of hospitalization. Subsequent data from the long-term extension study showed a mortality benefit in patients with NYHA class III HF,3 although data on long-term morbidity, functional capacity, and quality of life in these patients are lacking. Additional subgroup analysis results showed benefits in terms of mortality and morbidity in participants in the ATTR-ACT who were octogenerians.4

Although the Food and Drug Administration (FDA) approved tafamidis across the spectrum of disease irrespective of functional capacity and the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) Guideline for the Management of HF endorses its prescription as a Class 1 recommendation,5 the decision to prescribe tafamidis in frail, older adults with advanced disease requires a nuanced approach. Consistent with the process of shared decision-making, clinicians should carefully explain the benefits and risks of tafamidis in this population.6-8

Benefits include potential prolongation in survival with a therapy that has few to no adverse effects. However, given the high cost of tafamidis, financial toxicity is a risk for many patients who have significant out-of-pocket expenses.

Risks include living longer in a state of poor functional capacity and reduced quality of life with risks for recurrent hospitalization. This case illustrates the complexity of the decision-making process to prescribe a disease-modifying therapy for the cohort of older adults with ATTR-CA who experience multimorbidity, advanced HF, and frailty.


  1. Maurer MS, Schwartz JH, Gundapaneni B, et al.; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 2018;379:1007-16.
  2. Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol 2019;73:2872-91.
  3. Elliott P, Gundapaneni B, Sultan MB, Ines M, Garcia-Pavia P. Improved long-term survival with tafamidis treatment in patients with transthyretin amyloid cardiomyopathy and severe heart failure symptoms. Eur J Heart Fail 2023;25:2060-4.
  4. Garcia-Pavia P, Sultan MB, Gundapaneni B, et al. Tafamidis efficacy among octogenarian patients in the phase 3 ATTR-ACT and ongoing long-term extension study. JACC Heart Fail 2024;12:150-60.
  5. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2022;79:e263-e421.
  6. Fine NM, McMillan JM. Prevalence and prognostic significance of frailty among patients with transthyretin amyloidosis cardiomyopathy. Circ Heart Fail 2021;14:[ePub ahead of print].
  7. Cazalbou S, Naccache L, Sourdet S, et al.; Toulouse Amyloidosis Research Network. Frailty in older patients with transthyretin cardiac amyloidosis. J Clin Med 2023;12:[ePub ahead of print].
  8. Broussier A, David JP, Kharoubi M, et al. Frailty in wild-type transthyretin cardiac amyloidosis: the tip of the iceberg. J Clin Med 2021;10:[ePub ahead of print].

Clinical Topics: Geriatric Cardiology

Keywords: Geriatrics, Cardiac Amyloidosis

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