Abstract Background Introduction of disease-specific medication has revolutionized the management of transthyretin associated cardiomyopathy (ATTR-CM). However, dedicated trials included different patient populations, primary endpoints, and follow-up periods, rendering study comparison challenging. Purpose This systematic review and meta-analysis aimed to harmonize data from all phase-3 placebo-controlled drug trials in ATTR-CM to inform on the magnitude and timing of treatment efficacy of ATTR-specific medication. Methods We searched PubMed and Embase for trials published up to February 23rd, 2025. Efficacy outcomes included all-cause death, cardiovascular (CV-)events, change in 6-minute walk distance (6-MWD), NT-proBNP levels and Kansas-City Cardiomyopathy-Questionnaire-Overall-Score (KCCQ-OS). Outcome metrics were pooled across trials. Results We included data from four identified trials (ATTR-ACT, ATTRibute, APOLLO-B, HELIOS-B) and 2,086 patients. Baseline risk profiles and death rates of the respective placebo groups differed substantially between trials. At 12-months, ATTR-specific medication showed a trend toward less decline in 6-MWD (least squares mean LSM difference: 12.9 meters; 95%-CI -4.1 to 29.8) and was associated with a significantly blunted decline in KCCQ-OS (LSM difference: 4.7points; 95%CI 2.3-7.0) and NT-proBNP (geometric mean fold ratio: 0.80; 95%CI 0.74-0.85) compared to placebo. These effects were consolidated with continued treatment. Over the maximum follow-up period and at 30-months, respectively, ATTR-specific medication reduced the risk for all-cause mortality by 28% (HR 0.72; 95%CI 0.59-0.87) and for CV-events by 42% (OR 0.58; 95%CI 0.47-0.73). Conclusions ATTR-specific medication exhibits early salutary effects on blood biomarkers, functional capacity and quality of life. These effects translate into reductions in CV-events and all-cause mortality after continued treatment.Baseline characteristics and KM-curves Forest plots for outcomes.
Autherith et al. (Thu,) studied this question.