Health impact of tafamidis in transthyretin amyloid cardiomyopathy patients: an analysis from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and the open-label long-term extension studies

Abstract

Aim: The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) showed that tafamidis reduced all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to estimate the impact of tafamidis on survival and quality-adjusted life-years (QALYs).

Methods and results: A multi-state, cohort, Markov model was developed to simulate the disease course of ATTR-CM throughout a lifetime. For survival extrapolation, survival curves were fitted by treatment arm and New York Heart Association (NYHA) Class I/II (68% of patients) and NYHA Class III (32% of patients) cohorts using the individual patient-level data from both the ATTR-ACT and the corresponding long-term extension study. Univariate and multivariate sensitivity analyses were conducted. The predicted mean survival for the total population (NYHA Class I/II + III) was 6.73 years for tafamidis and 2.85 years for the standard of care (SoC), resulting in an incremental mean survival of 3.88 years [95% confidence interval (CI) 1.32-5.66]. Of the 6.73 life-years, patients on tafamidis spend, on average, 4.82 years in NYHA Class I/II, while patients on SoC spend an average of 1.60 life-years in these classes. The combination of longer survival in lower NYHA classes produced a QALY gain of 5.39 for tafamidis and 2.11 for SoC, resulting in 3.29 incremental QALYs (95% CI 1.21-4.74) in favour of tafamidis.

Conclusion: Based on the disease simulation model results, tafamidis is expected to more than double the life expectancy and QALYs of ATTR-CM patients compared to SoC. Longer-term follow-up data from the ATTR-ACT extension study will further inform these findings.

Clinical trials.gov identifier: NCT01994889 (date of registration: 26 November 2013).

Keywords: Cardiomyopathy; Mortality; Tafamidis; Transthyretin; Amyloidosis.

Figure 1

Model structure. NYHA, New York Heart Association Functional Classification.

Figure 2

Overview of observed and predicted survival for standard of care and tafamidis for (A) New York Heart Association I/II patients and (B) New York Heart Association III. NAR, number at risk; SoC, standard of care.

Figure 3

Predicted extrapolation and overall survival Kaplan–Meier for tafamidis and standard of care arms from Tafamidis in Transthyretin Cardiomyopathy Clinical Trial. SoC, standard of care.

Figure 4

Overview of (A) the mean and incremental mean survival and (B) quality-adjusted life-years by health state as predicted by the model. NYHA, New York Heart Association Functional Classification; QALYs, quality-adjusted life-years; SoC, standard of care.