"Tafamidis in Transthyretin Amyloid Cardiomyopathy".The New England Journal of Medicine. 2019. 379(11):1007-1016.PubMed•Full text•PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcomes
8.2 Secondary Outcomes
9 Funding
10 Further Reading

Clinical Question

In patients with transthyretin amyloid cardiomyopathy, does treatment with tafamidis reduce all-cause mortality and cardiovascular-related hospitalizations?

Bottom Line

In patients with transthyretin amyloid cardiomyopathy, treatment with tafamidis significantly reduced all-cause mortality and cardiovascular-related hospitalizations, as well as the decline in functional capacity and quality of life, compared with placebo.

Major Points

Transthyretin amyloid cardiomyopathy is characterized by the accumulation of amyloid fibrils composed of transthyretin protein in the heart, leading to cardiomyopathy and heart failure. Tafamidis is a benzoxazole derivative that binds to transthyretin, inhibiting its dissociation into monomers and subsequent amyloidogenesis.

Guidelines

As of the last update, no specific guidelines for the use of tafamidis in transthyretin amyloid cardiomyopathy were available.

Design

Multicenter, international, double-blind, placebo-controlled, phase 3 trial.

Population

441 patients with transthyretin amyloid cardiomyopathy.

Inclusion Criteria
- Between 18 and 90 years of age
- Transthyretin amyloid cardiomyopathy confirmed by biopsy or scintigraphy
- Cardiac involvement confirmed by echocardiography, history of heart failure, NT-proBNP level above 600 pg/ml, and a 6-minute walk-test distance over 100 m

Exclusion Criteria
- Heart failure not due to transthyretin amyloid cardiomyopathy
- NYHA class IV heart failure
- Light-chain amyloidosis
- History of organ transplantation
- Implanted cardiac device
- Previous tafamidis treatment
- Estimated glomerular filtration rate lower than 25 ml/min/1.73m²
- Liver transaminase levels exceeding two times the upper limit of normal

Baseline Characteristics
- Median age: 75 years
- Mostly male patients

Interventions

- 80 mg of tafamidis (n=264)
- 20 mg of tafamidis (n=264)
- Placebo (n=177)

Outcomes

Primary Outcomes
- Patients who received tafamidis had lower all-cause mortality and rate of cardiovascular-related hospitalizations than the placebo group (P<0.001), with a win ratio of 1.695.

Secondary Outcomes
- Improvement in the distance walked during the 6-minute walk test and KCCQ-OS scores, indicating reduced decline in functional capacity and quality of life, respectively.

Funding

Sponsored by Pfizer.

Further Reading

Further information can be found in the full text of the original article.