OBJECTIVES: ATTR-CM is a rapidly progressing, debilitating condition characterized by progressive heart failure and conduction disorders, leading to significant morbidity and mortality. Tafamidis, a TTR stabilizer, is the only approved ATTR-CM treatment; however, with multiple new therapies in late-stage development, it is important to understand the nature of disease worsening that may occur in patients receiving tafamidis, to clarify unmet need for new therapies and inform treatment decision-making. The current review synthesizes published data on the frequency of disease worsening with tafamidis in ATTR-CM.

METHODS: PubMed was searched for all publications with “tafamidis” in any search field that were published from January 2018 to February 2024. Publications retrieved underwent abstract screening to preliminarily assess their relevance to the research question: “What percentage of patients experience worsening of ATTR-CM while receiving tafamidis?” Publications identified as potentially relevant at this stage then underwent full-text screening, to yield a final set of relevant publications from which data on the target research question were extracted.

RESULTS: Overall, 391 references were retrieved for abstract screening; 60 advanced to full-text screening and ultimately 16 to data extraction. These 16 references suggest that among patients initiating tafamidis, worsening on “intermediate-term” (biomarker-based/surrogate) outcomes generally occurs in 40%–70% over 6–12 months, worsening as evidenced by need for hospitalization in 10%–30% over 12–24 months, and death in 5%–25% over 12–24 months.

CONCLUSIONS: Disease worsening as captured by intermediate-term (biomarker-based/surrogate) outcomes linked to morbidity and mortality may occur in more than half of patients over the first 6–12 months of tafamidis treatment. Accordingly, over the first 12–24 months of tafamidis treatment, downstream morbidity (hospitalization) and mortality occur in a substantial proportion of patients. These findings highlight the remaining morbidity/mortality burden in ATTR-CM, and the continued need for new treatments addressing this burden.