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The use of diflunisal for transthyretin cardiac amyloidosis: a review

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Abstract

Transthyretin cardiac amyloidosis (ATTR-CM) is caused by the accumulation of misfolded transthyretin (TTR) protein in the myocardium. Diflunisal, an agent that stabilizes TTR, has been used as an off-label therapeutic for ATTR-CM. Given limited data surrounding the use of diflunisal, a systematic review of the literature is warranted. We searched the PubMed, MEDLINE, and Embase databases for studies that reported on the use of diflunisal therapy for patients with ATTR-CM. We included English language studies which assessed the effect of diflunisal in adult patients with ATTR-CM who received diflunisal as primary treatment and reported clinical outcomes with emphasis on studies that noted the safety and efficacy of diflunisal in cardiac manifestations of ATTR amyloidosis. We excluded studies which did not use diflunisal therapy or used diflunisal therapy for non-cardiac manifestations of TTR amyloidosis. We also excluded case reports, abstracts, oral presentations, and studies with fewer than 10 subjects. Our search yielded 316 records, and we included 6 studies reporting on 400 patients. Non-comparative single-arm small non-randomized trials for diflunisal comprised 4 of the included studies. The 2 studies that compared diflunisal versus no treatment found improvements in TTR concentration, left atrial volume index, cardiac troponin I, and global longitudinal strain. Overall, diflunisal use was associated with decreased mortality and number of orthotopic heart transplant in ATTR-CM patients. Although a smaller number of patients had to stop treatment due to gastrointestinal side effects and transient renal dysfunction, there were no severe reactions reported in the studies included in our review. This systematic review supports the use of diflunisal for ATTR-CM. Additional long-term analyses and randomized clinical trials are needed to confirm these results.

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Abbreviations

ATTR-CM:

Transthyretin amyloid cardiomyopathy

TTR:

Transthyretin

hATTR:

Hereditary transthyretin amyloidosis

ATTRwt:

Wild-type transthyretin amyloidosis

OHT:

Orthotopic heart transplant

LV:

Left ventricle

EF:

Ejection fraction

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Authors and Affiliations

  1. Department Medicine, Division of Cardiovascular Medicine, Boston University Hospital, 801 Massachusetts Avenue Suite 400, Boston, MA, 02118, USA

    Michel Ibrahim & Leili Behrooz

  2. Division of Cardiology At Mount Sinai Medical Center, Columbia University, 4300 Alton Rd, Miami Beach, FL, 33140, USA

    Garly Rushler Saint Croix & Olivia Mechanic

  3. Department of Medicine, University of Miami Miller School of Medicine, 1120 NW 14th Street, Clinical Research Building, Miami, 33136, FL, USA

    Spencer Lacy

  4. Department of Internal Medicine Boston Medical Center, Boston University School of Medicine, 72 East Concord St, Boston, MA, 02118, USA

    Michael Fattouh & Maria Irene Barillas-Lara

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  1. Michel Ibrahim
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  2. Garly Rushler Saint Croix
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  3. Spencer Lacy
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  4. Michael Fattouh
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  6. Leili Behrooz
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Correspondence to Leili Behrooz.

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Ibrahim, M., Saint Croix, G.R., Lacy, S. et al. The use of diflunisal for transthyretin cardiac amyloidosis: a review. Heart Fail Rev 27, 517–524 (2022). https://doi.org/10.1007/s10741-021-10143-4

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  • DOI: https://doi.org/10.1007/s10741-021-10143-4

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