Comparative Effectiveness of TTR Stabilizers for the Treatment of ATTR-CM Using Real-World Evidence.

Authors

Richard Wright, Trejeeve Martyn, Allison Keshishian, Elizabeth Nagelhout, Bret Zeldow, Margarita Udall, David Lanfear, Daniel P Judge

Published in

Cardiology and therapy. Sep 23, 2026. Epub Sep 23, 2026.

Abstract

Progression of transthyretin amyloid cardiomyopathy (ATTR-CM) can cause worsening congestion, requiring diuretic intensification (DI), heart failure (HF)-related hospitalizations (HFH), and death. Acoramidis and tafamidis are approved for ATTR-CM, but head-to-head trials are lacking. We evaluated the real-world comparative effectiveness of acoramidis versus tafamidis in newly treated patients with ATTR-CM.
Retrospective study using Komodo Healthcare Map® US claims data tokenized to Claritas. Patients aged ≥18 years newly initiating acoramidis or tafamidis between 12/11/2024 and 04/30/2025 with ≥1 prescription claim (first defined as index date), ≥6 months continuous enrollment preindex date, no multiple myeloma, light chain amyloidosis, or hematopoietic stem cell treatments, and no prior treatments for ATTR-CM were included and followed until disenrollment, death, treatment switch, or study end (07/31/2025). Outcomes included DI (initiation or dose-equivalent escalation of oral loop diuretics, parenteral loop diuretic use, or addition of thiazide-like diuretic) and composite of DI, HFH (inpatient admission with HF-related International Classification of Diseases, 10th Revision, Clinical Modification, diagnosis code in any position), and mortality. Propensity score weighting balanced baseline characteristics, disease severity, comorbidity burden, and baseline medication use. Time-to-event outcomes were assessed using weighted Cox proportional hazards models.
After weighting, patients treated with acoramidis (n = 170) and tafamidis (weighted sample size = 448) were comparable. Mean follow-up was 139 and 143 days, respectively. DI cumulative incidence curves separated early and remained divergent. Acoramidis significantly reduced the hazard of DI events by 43% versus tafamidis (11.8% vs. 20.5%; hazard ratio [HR], 0.57; 95% CI, 0.35-0.92; p = 0.021). Acoramidis had a significantly lower risk of composite events, with a 34% hazard reduction compared with tafamidis (17.6% vs. 26.4%; HR, 0.66; 95% CI, 0.44-0.99; p = 0.046).
In this first real-world comparative effectiveness study of newly treated patients, acoramidis had a significantly lower risk of DI events and composite events of DI, HFH, and mortality than tafamidis, potentially supporting improved clinical stability with acoramidis initiation. Additional evaluation with longer follow-up, larger cohorts, and/or prospective clinical outcomes is warranted. Graphical abstract available for this article.

PMID:
42776416
Bibliographic data and abstract were imported from PubMed on 24 Sep 2026.

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