Key result
Acoramidis cuts cardiovascular hospitalizations ~34% compared to tafamidis in indirect comparison.
Why the study?
Heterogeneity across trials and imbalances in treatment effect modifiers make unadjusted indirect comparisons of acoramidis and tafamidis outcomes in ATTR-CM inappropriate.
Does acoramidis improve cardiovascular-related hospitalization and all-cause mortality compared to tafamidis 80 mg in patients with transthyretin amyloid cardiomyopathy?
Meta-Analysis (n=298)
Does acoramidis improve cardiovascular-related hospitalization and all-cause mortality compared to tafamidis 80 mg in patients with transthyretin amyloid cardiomyopathy?
In a matching-adjusted indirect comparison, acoramidis was associated with a 34% relative risk reduction in cardiovascular hospitalization compared to tafamidis in patients with ATTR-CM, though mortality outcomes were not significantly different.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“What these data do not clarify, however, is whether there is any difference in clinical benefit of acoramidis compared with tafamidis. In the ATTRibute-CM trial, the relative risk reduction of the composite endpoint of mortality and cardiovascular hospitalizations was driven primarily by a reduction in the risk of cardiovascular hospitalizations but not by a reduction in the risk of mortality.”
“The ICER evidence ratings for the TTR stabilizers reflect uncertainties around the magnitude of the clinical benefits in those patients who are currently being diagnosed with ATTR-CM; tafamidis showed large benefits in the original (more severe) population in which it was studied.”
“The significant reduction in diuretic intensification, an early indicator of worsening heart failure, points to improved disease control and clinical stability. The progressive nature of ATTR-CM is evident in all Phase 3 trials and is seen again here. This demonstrates the need for clinicians to proactively mitigate disease progression, and these data have the potential to meaningfully inform treatment selection in newly diagnosed patients and in patients currently on other treatments.”
Indirect comparison supports comparable efficacy between stabilizers; leaves open need for head-to-head trials to inform selection in ATTR-CM.
Aims Phase 3 trials have shown that acoramidis and tafamidis reduce the risk of all-cause mortality (ACM) and cardiovascular-related hospitalization (CVH) versus placebo in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Heterogeneity across trials and imbalances in treatment effect modifiers make unadjusted indirect comparisons of treatment outcomes inappropriate. We assessed the efficacy of acoramidis and tafamidis using population-adjusted indirect comparisons. Methods and Results We used matching-adjusted indirect comparison (MAIC) to assess the comparative efficacy of acoramidis and tafamidis 80 mg on reducing ACM and CVH over 30 months. We utilized individual patient data from ATTRibute-CM (acoramidis; NCT03860935) and published aggregate data from ATTR-ACT (tafamidis; NCT01994889) and adjusted for population differences. After adjusting for treatment effect modifiers and excluding data after initiation of concomitant tafamidis use in ATTRibute-CM, the effective sample size for ATTRibute-CM was 298 (acoramidis, n = 209; placebo, n = 89). In this MAIC model, acoramidis was associated with a 34% relative risk reduction in the cumulative frequency of CVH versus tafamidis (relative risk ratio 0.66; 95% CI 0.46–0.95). No statistically significant difference in ACM was observed between acoramidis and tafamidis, although the point estimate numerically favoured acoramidis (HR 0.72; 95% CI 0.41–1.26). No statistically significant differences were identified in the indirect comparisons of adverse events between acoramidis and tafamidis. Conclusion In an anchored MAIC, acoramidis was associated with improved outcomes, reflected by a lower risk of CVH versus tafamidis. In the absence of head-to-head data, these findings may offer important insights regarding the relative effectiveness of newer treatments in ATTR-CM.
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Masri et al. (2026) conducted a meta-analysis in Transthyretin amyloid cardiomyopathy (ATTR-CM) (n=298). Acoramidis vs. Tafamidis 80 mg was evaluated on Cumulative frequency of cardiovascular-related hospitalization (relative risk ratio 0.66, 95% CI 0.46-0.95). In a matching-adjusted indirect comparison, acoramidis reduced the cumulative frequency of cardiovascular hospitalizations by 34% compared to tafamidis (RR 0.66; 95% CI 0.46-0.95).
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