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).

Improved long‐term survival with tafamidis treatment in patients with transthyretin amyloid cardiomyopathy and severe heart failure symptoms

“…Previous analyses have demonstrated the value of long-term tafamidis treatment. 12,[22][23][24] These latest findings support previous data demonstrating that patients who received placebo in ATTR-ACT continued to have poorer survival in the LTE than those who initially received tafamidis. ATTR-ACT was not designed to assess efficacy in NYHA subgroups; however, pre-specified exploratory analyses have previously indicated a reduction in all-cause mortality with pooled tafamidis (80 and 20 mg) versus placebo in NYHA subgroups I-III.…”

Association of Tafamidis With Health Status in Patients With ATTR Cardiac Amyloidosis

“…In ATTR-ACT and the open-label extension, tafamidis was shown to more than double the life expectancy (6.73 vs 2.85 years) and quality-adjusted life-years in patients with ATTR cardiac amyloidosis vs standard of care . Although there was no interaction with NYHA class and all-cause mortality in ATTR-ACT, patients with NYHA class III symptoms had more cardiovascular-related hospitalizations in the tafamidis cohort ( P < .001 for interaction) compared with class II.…”

Tafamidis in patients with severe heart failure due to transthyretin amyloidosis cardiomyopathy: Improved long‐term survival

“…6 A moderate increase in life-years and quality-adjusted life-years (QALY) was observed in the model for patients with NYHA class III when placebo was compared with pooled tafamidis use (20 and 80 mg), respectively from 2.4 to 2.8 life-years and 1.6 to 2.1 QALY, larger improvements were observed in the model for NYHA class I and II from 3.1 to 8.6 life-years and from 2.3 to 7.0 QALY. 7 When interpreting the current study by Elliott et al in the context of the value of tafamidis in patients with NYHA III symptoms, it is relevant to note that the control group was treated with tafamidis for a large part of the follow-up time. This probably resulted in underestimation of the effect of tafamidis.…”

“…With regard to functionality, patients in NYHA III were 2.7 times more likely to have a 10 point improvement (95% CI 1.1–6.6; p = 0.03) in Kansas City Cardiomyopathy Questionnaire overall summary score after 30 months of tafamidis treatment compared to placebo 6 . A moderate increase in life‐years and quality‐adjusted life‐years (QALY) was observed in the model for patients with NYHA class III when placebo was compared with pooled tafamidis use (20 and 80 mg), respectively from 2.4 to 2.8 life‐years and 1.6 to 2.1 QALY, larger improvements were observed in the model for NYHA class I and II from 3.1 to 8.6 life‐years and from 2.3 to 7.0 QALY 7 …”