This was a retrospective longitudinal new-user, active-comparator claims cohort analysis of US patients from the Komodo Healthcare Map^®, with acoramidis data tokenized with Claritas (a data aggregator, which consolidates prescription data between specialty pharmacies and the acoramidis manufacturer’s hub) via Datavant token. The Komodo database complies with the Health Insurance Portability and Accountability Act. Given the deidentified nature of the data, patient consent and institutional review board approval were not required. Aggregate cohort-level results were reported. This study followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines for comparative effectiveness research.⁸

Patients were included if they were aged ≥18 years with ≥1 claim for acoramidis or tafamidis during the identification period from 12/11/2024 to 4/30/2025 and had ≥6 months of continuous enrollment before the index date (first acoramidis or tafamidis prescription). Patients were excluded if they had multiple myeloma, light chain amyloidosis, hematopoietic stem cell treatment at any time during the study period, had evidence of prior treatment with tafamidis, acoramidis, or a TTR silencer before the index date, or >1 ATTR-CM treatment on index date. Patients were followed until disenrollment, death, treatment switch, or study end date (7/31/2025).

The primary outcome was DI, defined as initiation or dose-equivalent escalation of oral loop diuretics, parenteral loop diuretics use, or addition of a thiazide-type diuretic. The secondary outcome was a composite of DI, HFH (inpatient admission with an HF-related ICD-10-CM diagnosis code in any position), and mortality. A subanalysis of oral loop DI was also conducted.

The statistical analysis plan followed the ISPOR guidelines,⁸ including the specification of the research question, prespecified analytical plans such as eligibility criteria, potential biases, outcome measures, handling of missing data, and all methods described herein. Categorical variables were summarized by frequency and percentage, and continuous variables by mean and SD. Propensity score weighting was used to balance baseline characteristics, time from diagnosis, measures of disease severity, comorbidity burden and medication use, including loop diuretics (Table 1). Collinearity was evaluated using variance inflation factors, and for highly correlated predictors, variables with greater clinical relevance and more robust data were retained. Logistic regression estimated the probability of receiving acoramidis based on prespecified covariates, and adequate balance was defined a priori as absolute standardized mean differences <0.1 for all covariates. Time-to-event outcomes were assessed using weighted Cox proportional hazards models for DI and oral loop DI separately and then for the first of any component of the composite, with tafamidis as the reference group. Kaplan-Meier estimates were used to assess the cumulative incidence of each outcome. Statistical significance was defined as two-sided P<0.05. We assessed falsification outcomes (any fracture, pneumonia, urinary tract infection, vaccination) to detect residual bias.