Disease-modifying treatments in transthyretin amyloid cardiomyopathy: a meta-analysis of randomized controlled trials

Abstract Background and Aims Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and life-threatening disease. With advancements in pharmacology, numerous novel medications are currently under investigation. However, the effects of these treatments on long-term outcomes remain elusive and inconclusive. Methods PubMed, MEDLINE, Embase, and the Cochrane Library were searched for literature inclusion until January 2024. Only phase 3, high-quality, randomized controlled trials related to ATTR-CM were considered for enrolment. Endpoints included all-cause mortality, six-minute walk distance, Kansas City Cardiomyopathy Questionnaire–Overall Summary Score, and serum N-terminal pro-B-type natriuretic peptide (NTproBNP) levels. A random-effects model was applied for meta-analysis. Results Three landmark trials (ATTR-ACT, APOLLO-B, ATTRibute-CM) comprising 866 patients with ATTR-CM were pooled. 66.6% of the subjects were administered with medical treatment. Consistent improvements in all-cause mortality (P=0.001), 6-minute walk distance (P=0.045), Kansas City Cardiomyopathy Questionnaire–Overall Summary Score (P<0.001), and serum NTproBNP level (P=0.002) were present by medical treatment. At 12 months, only NT-proBNP showed significant improvement in the pooled analysis of the APOLLO-B and ATTRibute-CM results. At 30 months, the pooled analysis of ATTR-ACT and ATTRibute-CM demonstrated significantly better all-cause mortality and KCCQ scores in patients received mediation. Conclusions Disease-modifying Treatments is associated with better survival, functional capacity, quality of life, and NTproBNP level in patients with ATTR-CM. Extended follow-up duration might be needed to demonstrate efficacies.