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

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. Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease caused by a protein called transthyretin. When misfolded, transthyretin forms harmful fibrils that can build up in the heart. Over time, ATTR-CM progresses and can worsen heart disease, requiring diuretic treatment or hospitalization. Diuretic intensification (the addition of new or increased diuretic therapy) is an early marker of heart failure progression and is associated with an increased risk of cardiovascular hospitalizations and death. The medicines acoramidis and tafamidis are used to treat ATTR-CM, with acoramidis being the most recent option available. Both prevent transthyretin from misfolding, but it is unknown if one leads to better outcomes. We compared their effectiveness in patients starting these medicines for the first time using patient medical billing records from December 2024 to April 2025. Specifically, we assessed how often patients experienced diuretic intensification, were hospitalized for heart failure, or died. We matched patient characteristics to ensure outcome differences were not due to differences between patients. We found that fewer patients treated with acoramidis required diuretic intensification compared with tafamidis (12% vs. 21%), resulting in a 43% lower risk of diuretic intensification. Additionally, fewer patients treated with acoramidis experienced diuretic intensification, hospitalization due to heart failure, or death compared with tafamidis (18% vs. 26%), resulting in a 34% lower risk of these combined events. These findings suggest that for patients with ATTR-CM, acoramidis may be better than tafamidis at preventing worsening heart problems. This information may help patients and doctors choose their treatment for ATTR-CM.