Measuring the Efficacy of Tafamidis as a Treatment for ATTR-CM

When a disease is progressive, it can be difficult to discern if treatment is working. Transthyretin amyloid cardiomyopathy (ATTR-CM) is an example, especially as its treatment, tafamidis, presents “relatively few side effects.” Because of this, medical professionals and patients are looking for measures of efficacy to better judge this drug. A recent article published in Healio touched upon an investigation of serum transthyretin as a marker of tafamidis’ efficacy.


First, it’s necessary to understand what this disease is. According to the American Heart Association, ATTR-CM is a rare, underdiagnosed form of amyloidosis that is characterized by deposits of amyloid protein fibrils in the left ventricle. These deposits stiffen the ventricle walls, making it difficult for the heart to relax, fill with blood, and squeeze blood out of the heart. There are two forms of this condition, one of which is hereditary while the other is wild-type. The former is the result of a mutated transthyretin gene, and it is passed from parent to child. In the United States, the most common mutation in this gene occurs in African Americans. The latter does not run in families, and it is severely underdiagnosed. Doctors are working to learn more about this form of ATTR-CM.

Symptoms include:

  • Coughing
  • Wheezing
  • Shortness of breath
  • Increased heart rate
  • Numb hands and/or feet
  • Bloating in the abdomen
  • Swelling in the ankles, legs, and feet
  • Confusion
  • Palpitations
  • Carpal tunnel syndrome

It is important to seek treatment for this condition, as it can lead to heart failure. Treatment is typically focused on preventing heart failure and its symptoms, along with stopping deposits of amyloid protein fibrils from forming. Medications for ATTR-CM are currently being developed as well, many of which are promising. In fact, VYNDAMAX (tafamidis) and VYNDAQEL (tafamidis meglumine) have both been approved. If the condition progresses to heart failure, a heart transplant may be necessary.

Serum Transthyretin as a Measure of Efficacy

A publication in JACC: CardioOncology investigated serum transthyretin as an efficacy marker for tafamidis. Participating researchers evaluated 72 patients with ATTR-CM being treated with tafamidis at Brigham and Women’s Hospital. After investigating this data, they compared it to prior research.

Within the group of patients, 67 had wild-type ATTR-CM, while the remaining five had variant transthyretin. Every patient had their transthyretin measured at baseline, after three months, and after twelve months. Results found:

  • Tafamidis led to an increase in serum transthyretin from 21.8 mg/dL to 29.3 mg/dL (34.5% increase)
    • The patients with variant transthyretin saw an increase of 70.9%
  • Insignificant increase in N-terminal pro-B-type natriuretic peptide (NT-proBNP)
  • Borderline significant increase in high-sensitivity troponin T

Looking Forward

These data are important for medical professionals to understand how to best evaluate the efficacy of tafamidis, especially as it comes at a high price of $225,000 annually and treats a progressive disorder.

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