Which patients did recent trials in transthyretin amyloid cardiomyopathy select? - Insights from a prospective patient registry
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Introduction
Several randomized, double-blind, placebo-controlled phase III trials (RCT) explore disease-modifying therapeutics in transthyretin amyloid cardiomyopathy (ATTR-CM). However, it is currently unclear whether patients eligible to participate in the RCT are representative of real-world patients.
Methods
ATTR-CM patients presenting to a tertiary referral center for cardiac amyloidosis at the Medical University of Vienna between March 2012 and May 2024 were included in a prospective cardiac amyloidosis registry. Inclusion and exclusion criteria of the ATTRACT, ATTRIBUTE, HELIOS-B, CARDIO-TTRANSFROM, and the DEPLETTR-CM trial were applied, and the baseline characteristics of the hypothetical trial cohorts as well as their survival were compared.
Results
A total of 353 patients (80.3 years, IQR: 75.5 – 84.2, 17.6% female) were included, out of which 192 patients would have been eligible to participate in ATTRIBUTE, ATTRACT would have recruited 163 patients, HELIOS-B 105 patients, CARDIO-TTRANSFROM 80 subjects, and 71 patients would have been eligible for DEPLETTR-CM.
Patients included in ATTRIBUTE, ATTRACT, HELIOS-B, and CARDIO-TTRANSFORM demonstrated only minor differences regarding baseline characteristics, both among each other and compared to the real-world cohort. However, patients eligible for the DEPLETTR-CM trial exhibited both more severely elevated biomarkers of heart failure (NT-proBNP: 2590pg/mL, IQR: 1614–4423, vs. 2339pg/mL, IQR: 1154–4250; p<0.001) as well more advanced disease assessed utilizing the New York Heart Association and National Amyloidosis Centre stage (p<0.001, respectively). Concerning all-cause mortality, patients who could have been included in DEPLETTR-CM also showed significantly worse survival. At the same time, no significant differences were observed between the real-world cohort and the other patient cohorts.
Conclusions
When applied to our real-world ATTR-CM cohort, recent RCT inclusion and exclusion criteria would have selected patients comparable to the real-world cohort. Only the DEPLETTR-CM trial would have selected patients with more advanced disease and worse prognosis in our cohort.
Clinical perspective
What’s new?
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This is the first study to assess whether patient cohorts in recent ATTR-CM trials represent real-world ATTR-CM patients.
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While this analysis suggests that ATTRACT, ATTRIBUTE, HELIOS-B, and CARDIO-TTRANSFROM would have included a somewhat representative patient sample, DEPLETTR-CM includes patients with more advanced disease.
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Females may have been underrepresented in recent ATTR-CM trials.
What are the clinical implications?
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These results may aid the interpretation of the trial results.
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This may be especially useful as currently there are no trials directly comparing ATTR-CM disease-modifying therapeutics.
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Finally, this analysis should support the design of future trials to be more representative of real- world ATTR-CM patients and more inclusive with regard to women and patients in very early disease stages.
