Outcomes with early access tafamidis in patients with variant transthyretin amyloid cardiomyopathy

Introduction

Tafamidis is a transthyretin stabilizer approved for patients with transthyretin amyloid cardiomyopathy (ATTR-CM) that demonstrated a significant reduction in all-cause mortality at 30 months in the pivotal phase III study (ATTRACT). After completing the phase 3 trial all patients could enrol in a long-term extension study to receive treatment. An independent cohort was also added to allow early-access to tafamidis for patients who had not taken part in ATTR-ACT.

Purpose

Evaluate outcomes in patients with variant ATTR-CM (ATTRv-CM) who received early access tafamidis in the independent cohort.

Methods

Minimal enrolment criteria were applied to the independent early access cohort. Among the 1476 patients treated in the independent cohort, 212 (14.4%) had ATTRv-CM and were included in this analysis. Patients received open-label tafamidis free acid 61 mg once daily for up to 60 months. Outcomes included: incidence of all-cause mortality (including heart transplant and cardiac mechanical assist device) and cardiovascular (CV)-related mortality; frequency of all-cause and CV-related hospitalisations; change from baseline in New York Heart Association (NYHA) functional classification, and Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score.

Results

ATTRv patients were most commonly V142I (8.9%), had a mean age of 70.2 years, and were mostly Black or African American (52.8%). At baseline, 16.0%, 49.5%, 32.1%, and 2.4% of patients with ATTRv-CM were NYHA class I, II, III, and IV, respectively, and the mean (SD) KCCQ-OS score was 64.0 (26.3).

The median (range) duration of treatment was 12.7 (0ꟷ54.5) months. Most patients with ATTRv-CM had a stable or improved NYHA class throughout follow-up (Table). Change from baseline in KCCQ-OS score was minimal over 54 months, indicative of stable quality of life (Figure). The incidence of all-cause mortality during the study was 19.3% in patients with ATTRv-CM, and the incidence of CV-related mortality was 10.4%. In patients with ATTRv-CM, the total annual rate of all-cause hospitalisation and CV-related hospitalisations was 0.50 and 0.31, respectively. No new safety signals were identified.

Conclusion

Patients with ATTRv-CM who received early-access tafamidis treatment had stable or improved heart failure symptoms, consistent quality of life, and similar mortality and safety as seen in the overall population.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.