Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM: Exploratory Analysis From
Ahmad Masri1, Daniel P Judge2, Frederick L Ruberg3
1Oregon Health and Science University, Portland, Oregon, USA.
Insights
Acoramidis significantly reduced the cumulative burden of cardiovascular events in transthyretin amyloid cardiomyopathy (ATTR-CM) over 30 months. Early intervention with acoramidis is crucial, as nearly a quarter of events occurred within the first six months.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Transthyretin amyloid cardiomyopathy (ATTR-CM) presents a high burden of recurrent cardiovascular (CV) events.
- Acoramidis, an oral therapy, effectively stabilizes transthyretin (TTR).
- Previous studies showed acoramidis reduced the composite of mortality or first CV hospitalization (CVH) in ATTR-CM.
Purpose of the Study:
- To perform a post hoc exploratory recurrent-event analysis of acoramidis' efficacy on cumulative CV outcomes.
- To evaluate the impact of acoramidis on the incidence of recurrent CV events in ATTR-CM patients.
Main Methods:
- A modified Andersen-Gill model was used to analyze cumulative incidences of CV-related mortality (CVM) or recurrent CVH.
- The analysis included the modified intention-to-treat population from the ATTRibute-CM study and its open-label extension.
- Event data were assessed up to month 30 for CVM or recurrent CVH, and up to month 42 for CVM.
Main Results:
- Acoramidis significantly reduced the cumulative risk of CVM or recurrent CVH by 49% through 30 months (HR: 0.51; P < 0.0001).
- A substantial proportion of CV events (19-22%) occurred within the first six months.
- By month 30, acoramidis demonstrated 53 avoided events per 100 participants compared to placebo, with continuous treatment reducing CVM at 42 months (HR: 0.55; P = 0.0011).
Conclusions:
- Acoramidis significantly lowers the cumulative burden of CV outcomes in ATTR-CM over 30 months.
- The early occurrence of CV events highlights the importance of prompt diagnosis and treatment initiation.
- These findings underscore the benefit of acoramidis in managing the progressive nature of ATTR-CM.
Background:
Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a progressive disease with a significant burden of recurrent cardiovascular (CV) events. Acoramidis, an approved oral therapy for ATTR-CM, achieves early, near-complete (≥90%) TTR stabilization. In the phase 3 ATTRibute-CM (Efficacy and Safety of Acoramidis in Participants with Transthyretin Amyloid Cardiomyopathy) study, acoramidis significantly reduced the composite of all-cause mortality or first CV-related hospitalization (CVH), with an effect observed at month 3. Its efficacy on the burden of cumulative CV outcome events has not been reported.
Objectives:
This study was a post hoc exploratory recurrent-event analysis of the efficacy of acoramidis on the cumulative incidence of CV outcomes from ATTRibute-CM and its open-label extension.
Methods:
Cumulative incidences of centrally adjudicated CV-related mortality (CVM) or recurrent CVH (first and, if applicable, subsequent CVH), recurrent CVH alone (month 30), and CVM (month 42) were measured in the modified intention-to-treat population (acoramidis, n = 409; placebo, n = 202). Mean cumulative events by treatment, and the difference between treatment groups were estimated by using a modified Andersen-Gill model.
Results:
Acoramidis significantly reduced the cumulative risk of CVM or recurrent CVH through month 30 vs placebo (HR: 0.51; 95% CI: 0.43-0.62; P < 0.0001). A notable proportion of CV outcome events (19% of CVM or recurrent CVH events, 22% of CVH) occurred within the first 6 months. Numerically fewer cumulative events were observed with acoramidis compared with placebo at month 1, and the difference increased progressively, resulting at month 30 in 53 events avoided per 100 treated participants (95% CI: 29-79). At month 42, CVM was reduced with continuous acoramidis vs placebo-to-acoramidis (HR: 0.55; 95% CI: 0.39-0.79; P = 0.0011). The annualized frequency of recurrent CVH was significantly decreased through month 30 (relative risk ratio: 0.50; 95% CI: 0.35-0.69; P < 0.0001).
Conclusions:
Acoramidis significantly reduced the cumulative burden of CV outcomes in ATTR-CM over 30 months. Numerically fewer events were observed with acoramidis vs placebo by month 1, and the difference increased progressively over time, resulting in 53 events avoided per 100 treated patients at month 30. Almost one-fourth of the cumulative CV events occurred within the first 6 months. These exploratory findings suggest that cumulative event burden may occur early, highlighting the importance of timely evaluation, diagnosis and treatment in ATTR-CM.
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