The effect of quality of life on all cause mortality in tafamidis treated vs. placebo ATTR-CM patients: post hoc analyses from the ATTR-ACT study

Background/Introduction In ATTR CM, deterioration in health related quality of life (QoL) is common and prognostically relevant. Tafamidis is the only near-complete TTR kinetic stabilizer for treating transthyretin amyloid cardiomyopathy (ATTR-CM) that is administered orally once daily and has demonstrated a statistically significant reduction in mortality at 30 months compared with placebo. Purpose This post hoc analysis of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) study evaluated the correlation of trajectories of patient reported QoL (Kansas City Cardiomyopathy Questionnaire–Overall Summary [KCCQ-OS] and EuroQol Visual Analogue Scale [EQ VAS]) with all cause mortality (ACM), and assessed the effect of tafamidis (80mg) on ACM after accounting for changes in QoL. Methods QoL was assessed every 6 months using KCCQ-OS and EQ VAS. Patients were categorized as “improved/maintained” for >-5 points (KCCQ-OS change from baseline [CFB]) and for >-3 points (EQ VAS CFB), respectively, or otherwise “worsened” at each visit. The last observation carried forward method was used for the missing assessments until death. Least squares mean for CFB were obtained from the mixed models for repeated measures at each visit through Month 30. The hazard ratios (HR) (95% CI) of ACM comparing “improved/maintained” versus “worsened” at each visit were obtained from the Cox proportional hazard model adjusted for baseline scores for tafamidis 80mg and placebo separately. The time dependent Cox models evaluated ACM risk (tafamidis vs. placebo), adjusting for time-varying KCCQ-OS status, or time-varying EQ VAS status in separate models. Results For KCCQ-OS, 176 tafamidis and 177 placebo patients were assessed at baseline with CFB scores decreasing to 110 and 84 at Month 30, respectively. In total, there were 54 versus 76 ACM events, respectively. The ACM HR for tafamidis vs. placebo adjusted for time varying KCCQ-OS status was 0.65 (95% CI 0.43–0.99) (Fig. 1). Among patients treated with tafamidis 80 mg, KCCQ-OS improved with significant ACM hazard reduction (59~78%) than those with deterioration in KCCQ-OS at all visits (Month 12~30). This effect was not observed in patients in the placebo group. Similar findings were observed with EQ VAS, with HR of 0.65 (95% CI 0.44–0.97) for tafamidis vs. placebo adjusted for time varying EQ VAS status over 30 months (Fig. 2). In patients treated with tafamidis 80 mg, EQ VAS improved with significant ACM hazard reduction (53~73%) than those with deterioration in EQ VAS at Month 12, 18 and 24. Conclusions In this post-hoc analysis, tafamidis reduced ACM even after adjusting for time-varying QoL status. Longitudinal QoL trajectories act as dynamic prognostic indicators for ATTR CM.Figure 1Figure 2