Modeling of Survival and Frequency of Cardiovascular-Related Hospitalization in Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis

• Published in: American journal of cardiovascular drugs : drugs, devices, and other interventions devices, and other interventions, 2021-09, Vol.21 (5), p.535-543
• Main Authors: Vong, Camille, Boucher, Martin, Riley, Steve, Harnisch, Lutz O.
• Format: Article
• Language: English
• Subjects: Amyloidosis; Binding sites; Cardiology; Cardiomyopathy; Clinical trials; Ejection fraction; Heart transplants; Hospitalization; Medical prognosis; Medicine; Medicine & Public Health; Mortality; Original; Original Research Article; Patients; Peptides; Pharmacology/Toxicology; Pharmacotherapy
• ISSN: 1175-3277; 1179-187X
• DOI: 10.1007/s40256-021-00464-y

Introduction ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) demonstrated the efficacy and safety of tafamidis in transthyretin amyloid cardiomyopathy (ATTR-CM). Model-based analyses from ATTR-ACT can examine predictor effects on dose–response/exposure–response relationships. Methods Parametric hazard distributions were developed for all-cause mortality and frequency of cardiovascular-related hospitalization. Time-to-event models were fitted to survival data, and repeated time-to-event models were fitted to hospitalization data. Disease-specific characteristics were assessed as baseline predictors of event hazards. Results There were 441 patients in this analysis. At month 30, 70.5% (tafamidis) and 57.1% (placebo) of patients were alive, with 154/441 deaths reported; 495 cardiovascular-related hospitalizations occurred. The cumulative risk of death was 42.1% (95% confidence interval [CI] 24.2–58.0) lower with tafamidis than with placebo, regardless of New York Heart Association (NYHA) class; significant predictors of decreased risk were genotype (wild-type), greater 6-Minute Walk Test (6MWT) distance, higher left ventricular ejection fraction (LVEF), and lower blood urea nitrogen (BUN) and N-terminal pro-B-type natriuretic peptide concentrations. The average cumulative risk of cardiovascular-related hospitalization up to 30 months was 40.8% (95% CI 31.0–49.7) lower with tafamidis in NYHA class I/II patients. Significant predictors of reduced risk were greater 6MWT distance, higher LVEF, and lower BUN and troponin I concentrations. Conclusions Tafamidis reduced cumulative mortality and hospitalization risk versus placebo in patients with ATTR-CM. Baseline predictors of outcome were consistent with the cardiovascular nature of the disease and suggested that earlier treatment may improve outcomes. Clinical Trials.gov Identifier NCT01994889 (date of registration: November 26, 2013).