Tafamadis for Patients with Transthyretin Amyloid Cardiomyopathy

Transthyretin Amyloid Cardiomyopathy occurs with one (or more) mutations to the TTR gene.  With any substitution to this gene, it becomes unstable and results in misfolding and production of amyloid fibers, which then infiltrate the myocardium.  Clinical manifestations often vary depending on the individual and the genetic substitution and can yield neuropathies, cardiomyopathy or both.  In the United States, there are believed to be less than 6,500 people with Transthyretin Amyloid Cardiomyopathy.  However, given the significant impact this mutation / disease has on the quality of life of those affected, the FDA recently approved a medication that helps to reduce disease progression and prolong life expectancy.

During my Family Medicine rotation, I saw one of Dr. Streete-Smalls’ patient who was diagnosed with Transthyretin Amyloid Cardiomyopathy and was a part of the Phase 4 clinical trial of the medication.  Given the fact that the medication moved to Phase 4, it was worthy of evaluation and review especially as a patient in the office was now taking this medication.

The article selected reviews the Phase 3 trial assessing the use of Tafamidis to help treat Transthyretin Amyloid Cardiomyopathy.  This double-blind, placebo-controlled study randomly assigned 441 patients (264 received different doses of Tafamidis and 177 received placebo pills) over a 30 month period to assess functionality and effectiveness.  The authors evaluated all-cause mortality, followed by frequency of cardiovascular-related hospitalizations as their primary analysis and looked at the Kansas City Cardiomyopathy Questionnaire-Overall Summary to assess changes from baseline as their secondary analysis.

The study ultimately resulted that Tafamidis reduced all-cause mortality and cardiovascular-related hospitalizations and reduced the decline in functional capacity and quality of life (in comparison to the placebo) with 95% confidence interval.  The authors also found that there was a lower rate of decline on the KCCQ-OS score and a lower rate of decline in distance for the 6-minute walk test.  These findings show that Tafamidis is having a positive impact on patients with Transthyretin Amyloid Cardiomyopathy and improving their quality of life.  In reading other articles / publications on Tafamidis, I found an article that assessed the safety and effectiveness of the drug, which resulted in the fact that Tafamidis is safe and effective up to 6 years in clinical practice and in today’s climate there are no unexpected adverse effects with long-term use of the medication.

Given the success of the phase 3 trial, my hope would be that this medication continues to offer a safe an effective treatment option for patients with Transthyretin Amyloid Cardiomyopathy.  Pfizer, the company that manufactures Tafamidis, funded the clinical trials thus far, which is to be expected at such early stages of research.  However, I would like to see companies fund research to provide another layer of insight to ensure the drug is truly safe and effective for patients to use in clinical practice, as the drug becomes more mainstream.

https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-amyloid-cardiomyopathy?topicRef=85952&source=see_link#H1
http://www.amyloidosis.org/wp-content/uploads/2017/05/2017-ATTR-guide.pdf
https://www.tandfonline.com/doi/full/10.1080/13506129.2017.1357545

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