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Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy - ATTRibute-CM
Contribution To Literature:
Highlighted text has been updated as of January 22, 2024.
The ATTRibute-CM trial showed that acoramidis HCl is superior to placebo for improving both hard CV endpoints as well as quality of life endpoints among patients with ATTR-CM.
Description:
The goal of the trial was to compare the safety and efficacy of acoramidis compared with placebo among patients with transthyretin amyloid cardiomyopathy (ATTR-CM).
Study Design
Eligible patients were randomized in a 2:1 randomized double-blinded fashion to either acoramidis HCl (n = 421) or matching placebo (n = 211). Acoramidis was administered at a dose of 800 mg BID for 30 months.
- Total number of enrollees: 632
- Duration of follow-up: 30 months
- Mean patient age: 77.3 years
- Percentage female: 10%
Inclusion criteria:
- Age 18-90 years
- Met the following two criteria: diagnosed ATTR-CM (wild-type [WT] or variant); New York Heart Association (NYHA) class I-III with ≥1 hospitalization for heart failure (HF); signs and symptoms of volume overload; HF that resulted in diuretic treatment; ATTR-positive biopsy or technetium-99m scintigraphy (99mTc) scan; light chain amyloidosis excluded if diagnosis by 99mTc
- Six-minute walk distance ≥150 m
- N-terminal pro–B-type natriuretic peptide (NT-proBNP) ≥300 pg/mL
- Left ventricular wall thickness ≥12 mm
Exclusion criteria:
- Acute coronary syndrome, stroke, transient ischemic attack, or coronary revascularization within 90 days
- Likely heart transplant within 1 year
- AL amyloidosis
- Transaminitis
- NT-proBNP ≥8500 pg/mL
- Estimated glomerular filtration rate <15
Other salient features/characteristics:
- ATTRwt-CM: 90.4%
- NT-proBNP: 2326 pg/mL
- Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS) at baseline: 71
- Concomitant tafamidis use: 18%
Principal Findings:
The primary endpoint, a hierarchical analysis consisting of all-cause mortality, cumulative frequency of cardiovascular (CV)-related hospitalization, change from baseline in NT-proBNP, and change from baseline in 6-minute walk distance, had an overall win ratio favoring acoramidis (win ratio 1.8, 95% confidence interval [CI] 1.4-2.2, p < 0.0001).
Secondary outcomes for acoramidis vs. placebo:
- All-cause mortality: 19.3% vs. 25.7%; hazard ratio (HR) 0.77, 95% CI 0.54-1.10 (p = 0.15)
- Adjusted mean factor change in NT-proBNP from baseline: 0.529 (95% CI 0.46-0.60, p < 0.05)
- Improvement from baseline in 6-minute walk distance: 39.6 m (95% CI 21.1-58.2, p < 0.001)
- CV-related hospitalization: 26.7% vs. 42.6% (p < 0.0001)
- Least means square change in KCCQ-OS: 9.94 points (95% CI 5.97-13.91, p < 0.001)
Composite of all-cause mortality and CV-related hospitalization: HR 0.65, 95% CI 0.50-0.83 (p = 0.0008; number needed to treat = 7)
Interpretation:
The results of this trial indicate that acoramidis 800 mg BID is superior to placebo for improving both CV endpoints (primarily CV-related hospitalization) as well as surrogate (NT-proBNP) and quality of life endpoints among patients with ATTR-CM. Both tafamidis and acoramidis are stabilizers of transthyretin. Acoramidis has the potential to be an effective and safe alternative to tafamidis for the treatment of ATTR-CM. A head-to-head comparison and cost considerations are important next steps.
References:
Gillmore JD, Judge DP, Cappelli F, et al., on behalf of the ATTRibute-CM Investigators. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. N Engl J Med 2024;390:132-42.
Presented by Dr. Daniel Judge at the American Heart Association Scientific Sessions, Philadelphia, PA, November 12, 2023.
Presented by Dr. Julian Gillmore at the European Society of Cardiology Congress, Amsterdam, Netherlands, August 27, 2023.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure
Keywords: AHA23, Amyloid, Cardiomyopathies, Heart Failure
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