Stage-dependent timing of relative and absolute treatment benefit in transthyretin amyloid cardiomyopathy
Year: 2026
Type: article
Abstract: BACKGROUND: In transthyretin amyloid cardiomyopathy (ATTR-CM), treatment effects are often delayed and stage-dependent, which complicates interpretation of a single HR. The timing of relative and absolute benefit at each stage is unclear. We examined stage-specific treatment effects of tafamidis using complementary time-to-event analyses. METHODS: Individual patient-level data were reconstructed from published Kaplan-Meier curves of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial long-term extension and analysed by National Amyloidosis Centre (NAC) stage. Time to benefit (TTB) was estimated from flexible parametric (Royston-Parmar) models with time-varying treatment effects, providing time-varying HRs and absolute risk reduction and was cross-checked with truncated Cox and restricted mean survival time (RMST) trajectory analyses. RESULTS: Effects differed by NAC stage. Tafamidis reduced mortality in NAC1 (HR 0.45, 95% CI 0.27 to 0.73) and NAC2 (HR 0.55, 95% CI 0.35 to 0.86); no effect was seen in NAC3. Hazard reduction was early and consistent in NAC1 but delayed in NAC2. HR-based TTB was 36 months in NAC1 and 50 months in NAC2 and was not reached in NAC3. RMST-based TTB occurred later (38 and 61 months). At maximum follow-up, RMST gain was 17 months in NAC1, 13 months in NAC2 and 1 month in NAC3. CONCLUSIONS: Survival benefit from tafamidis is stage-dependent, appearing earlier and lasting longer in less advanced disease. In intermediate-stage disease, relative effects preceded—and at times diverged from—absolute survival gains. These data support early initiation of therapy and the use of complementary analytical approaches alongside the conventional HR.
Source: Open Heart
Institution: Saga University
Language: English
Subfield: Internal Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,391
OpenAlex ID: W7223707615