Journal of the American College of Cardiology最新文献

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.

Background: Timely diagnosis and treatment are critical to reduce morbidity and mortality for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Limited existing data suggest underdiagnosis of ATTR-CM and inequity in predictors of diagnosis patterns.

Objective: This study sought to describe the time from heart failure (HF) diagnosis to ATTR-CM diagnosis and identify predictors for delayed diagnosis of ATTR-CM.

Methods: This retrospective cohort study used Veterans Health Administration (VHA) data. We identified patients with HF and ATTR-CM diagnosed between 2016 and 2022 using an algorithm based on diagnoses and medications. The primary outcome was the time to diagnosis of ATTR-CM and was defined as the number of days between each patient's first HF diagnosis and their first ATTR-CM diagnosis. We also evaluated the number of days between first HF hospitalization or first loop diuretic prescription and ATTR-CM diagnosis. We used multivariable logistic regression to assess demographic, clinical, and socioeconomic predictors of time to ATTR-CM diagnosis using >6 months as a meaningful delay.

Results: A total of 2,557 patients with HF and ATTR-CM were identified. The mean age at the time of ATTR-CM diagnosis was 81 years. Most veterans were male (2,544; 99.5%) and White (1,440; 56%). The median time to diagnosis to ATTR-CM was 490 days. For the 1,882 veterans with a loop diuretic prescription before ATTR-CM diagnosis, the median time between initial loop prescription and ATTR-CM diagnosis was 835 days (Q1-Q3: 250-1850). Across Department of Veterans Affairs sites, the median number of days to diagnosis ranged from 169 to 1,070 days. After adjustment, Black race (OR: 0.71; 95% CI: 0.57-0.88) and older age (OR: 0.66; 95% CI: 0.59-0.73) were associated with a shorter time to diagnosis, whereas a history of atrial fibrillation (OR: 1.21; 95% CI: 1.00-1.45), coronary artery disease (OR: 1.38; 95% CI: 1.15-1.64), or chronic kidney disease (OR: 1.79; 95% CI: 1.50-2.15) was associated with longer time to diagnosis.

Conclusions: There are clinically important delays between incident HF and diagnosis of ATTR-CM. Carrying a diagnosis of atrial fibrillation, coronary artery disease, or chronic kidney disease was associated with a longer delay to diagnosis. These findings uncover an opportunity for clinicians to consider concomitant ATTR-CM in patients with alternate etiologies for their cardiomyopathy, as expediting evaluation for ATTR-CM following HF diagnosis is critical to reduce the morbidity of this progressive condition.