DEPLETTR-CM trial selected ATTR-CM patients with more advanced disease and worse survival (NT-proBNP 2590 pg/mL vs 2339 pg/mL; p<0.001) vs other recent trials.
Are patients eligible for recent ATTR-CM RCTs representative of real-world patients in terms of baseline characteristics and survival?
Most recent ATTR-CM RCTs select patients representative of real-world cohorts, with the exception of DEPLETTR-CM which selects for more advanced disease.
Absolute Event Rate: 0% vs 0%
Abstract Introduction Several randomised 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 participation in the RCT are representative of real-world patients. We therefore explored differences between a real-world ATTR-CM cohort and the subgroups of patients who would have been eligible for inclusion in the ATTRACT, ATTRIBUTE, HELIOS-B, CARDIO-TTRANSFORM, and DEPLETTR-CM trials. Methods ATTR-CM patients presenting to a tertiary referral centre 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 respective RCT 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 inclusion in DEPLETTR-CM. Patients included in ATTRIBUTE, ATTRACT, HELIOS-B, and CARDIO-TTRANSFORM demonstrated only minor differences with regard to baseline characteristics, both among each other as well as compared to the real-world cohort. However, patients eligible to the DEPLETTR-CM trial exhibited both more severely elevated biomarkers of heart failure (NT-proBNP: 2590 pg/mL, IQR: 1614–4423, vs. 2339 pg/mL, IQR: 1154–4250; p0.001) as well more advanced disease assessed utilising the New York Heart Association and National Amyloidosis Centre stage (p0.001, respectively). With regard to all-cause mortality, patients who could have been included in DEPLETTR-CM also showed significantly worse survival, while no significant differences were observed between the real-world cohort and the other patient cohorts. Conclusion When applied to our real-world ATTR-CM cohort, recent RCT inclusion and exclusion criteria would have selected patients which are rather 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.
Poledniczek et al. (Sat,) reported a other. DEPLETTR-CM trial selected ATTR-CM patients with more advanced disease and worse survival (NT-proBNP 2590 pg/mL vs 2339 pg/mL; p<0.001) vs other recent trials.