First Comparison of Diflunisal and Tafamidis in Patients with Transthyretin Amyloid Cardiomyopathy

Gilad and colleagues at the Amyloidosis Center at Boston University School of Medicine and Boston Medical Center presented results of a study comparing therapies for transthyretin amyloid cardiomyopathy (ATTR-CM), which increasingly is being recognized as a cause of heart failure. This evaluation may be of interest to clinicians because previously no study had compared the 2 therapies in patients with ATTR-CM.

In 2019, tafamidis became the first FDA-approved treatment for ATTR-CM after demonstrating lower rates of all-cause mortality and cardiovascular-related hospitalizations compared with placebo.1 Although it is the first FDA-approved therapy for ATTR-CM, tafamidis often has high patient copayments. With treatment costing approximately $225,000 per year, many patients’ copayments total thousands of dollars per month. Diflunisal is a generic nonsteroidal anti-inflammatory drug with a mechanism of action similar to tafamidis and has been used previously in patients with ATTR-CM.

The investigators retrospectively evaluated patients who were initiated on diflunisal (N = 43), tafamidis (N = 23), or neither (control; N = 62) from 2009 to 2020. For 110 patients, a 1-year follow-up was performed. Tafamidis was prescribed as first-line therapy after FDA approval in May 2019; patients who could not afford tafamidis or who were treated prior to tafamidis approval were included in the diflunisal cohort.

In the treated groups, New York Heart Association Functional Classification, plasma B-type natriuretic peptide, cardiac troponin, and prealbumin were similar; higher disease biomarkers were exhibited by controls. At 1 year, the researchers reported no significant difference in disease markers between treated groups, although there was a trend of higher prealbumin levels noted in the diflunisal group. The greatest estimated glomerular filtration rate reduction was reported in the diflunisal group; however, at 1 year, when compared across groups, estimated glomerular filtration rate was noninferior (P = .46). The authors concluded that although no study has previously compared diflunisal and tafamidis in patients with ATTR-CM, when comparing treatment cohorts at 1 year, there was no difference in biomarker progression. Ongoing studies are warranted, and longer follow-up is needed. Based on the preliminary results of this study, for patients with financial concerns, diflunisal may be a reasonable alternative to treatment with tafamidis.

Source: Gilad A, Joshi T, Mendelson L, et al. Treating transthyretin amyloid cardiomyopathy: a comparison of diflunisal and tafamidis. Presented at: ACC.21, the American College of Cardiology 70th Annual Scientific Session & Expo, May 15-17, 2021. Poster 21659.


1. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007-1016.

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