(P105) IMPROVED SURVIVAL WITH ~5 YEARS OF CONTINUOUS TAFAMIDIS TREATMENT AMONG PATIENTS WITH NYHA CLASS III TRANSTHYRETIN AMYLOID CARDIOMYOPATHY

Background: Treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in patients with severe heart failure symptoms (New York Heart Association [NYHA] class III) has been debated. Tafamidis is the only approved treatment for this fatal disease. This analysis assessed survival by NYHA class in patients with ATTR-CM in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and its ongoing long-term extension (LTE) study.

METHODS AND RESULTS: In ATTR-ACT, patients received tafamidis meglumine (80 or 20 mg) or placebo for up to 30 months. Patients completing ATTR-ACT could enrol in the LTE to receive tafamidis meglumine (same dose as in ATTR-ACT; placebo patients randomised 2:1 to 80 mg or 20 mg). Following a protocol amendment, patients transitioned to tafamidis free acid 61 mg (bioequivalent to tafamidis meglumine 80 mg). In an interim analysis, survival with continuous high-dose tafamidis (80 mg/61 mg) or placebo to tafamidis (placebo in ATTR-ACT then tafamidis in the LTE) was evaluated over ~5 years using a Cox proportional hazards model for patients with NYHA classifications of I/II, or III at baseline. Treatment and transthyretin genotype (variant and wild type) were included in the model. At baseline, 121 (68.8%) of 176 patients in the continuous tafamidis group (80 mg/61 mg) were NYHA class I/II and 55 (31.3%) were NYHA class III; 114 (64.6%) of 177 in the placebo to tafamidis group were NYHA class I/II and 63 (35.6%) class III. A trend for reduced all-cause mortality with continuous tafamidis treatment strengthened alongside length of observation in the LTE for both NYHA subgroups. In all LTE analyses, treatment with continuous tafamidis was associated with a lower risk of all-cause mortality than treatment with placebo to tafamidis in patients who were NYHA class I/II at baseline. In the data cut representing a median follow-up of ~5 years, the risk of all-cause mortality was lower in both subgroups, including patients who were NYHA class III (hazard ratio: 0.636; 95% confidence interval: 0.408, 0.992; p=0.0460; Table). The safety profile for tafamidis remains consistent with that of ATTR-ACT.

Conclusion: In patients continuously treated with tafamidis, a reduction in all-cause mortality was observed in patients in all NYHA classes (I/II and III) over a median follow-up of ~5 years. Our findings not only support the use of tafamidis in all patients with ATTR-CM, including the most severe symptoms (NYHA class III), but further emphasize the importance of early diagnosis and continued treatment. NCT01994889; NCT02791230