Long‐term tafamidis efficacy in patients with transthyretin amyloid cardiomyopathy by baseline left ventricular ejection fraction

Abstract

AbstractAimsPatients with transthyretin amyloid cardiomyopathy (ATTR‐CM) present with diverse left ventricular ejection fraction (LVEF). This study assessed tafamidis efficacy by baseline LVEF in the phase 3 Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR‐ACT) and its long‐term extension (LTE) study.Methods and resultsPatients were randomized to 30 months of tafamidis or placebo treatment in ATTR‐ACT. On completion, patients could join an LTE study to receive tafamidis. All‐cause mortality (death, heart transplant, or cardiac mechanical assist device implantation) from baseline to the end of follow‐up was assessed in patients continuously treated with tafamidis (80 mg meglumine or 61 mg free acid) or delayed tafamidis treatment (placebo in ATTR‐ACT; tafamidis in the LTE study) according to baseline LVEF (<50% or ≥50%). Supportive outcomes were evaluated over a shorter follow‐up. Patients with baseline LVEF <50% (n = 177: 88 tafamidis‐ and 89 placebo‐treated) had signs of more severe heart failure, a higher proportion were Black, and had variant ATTR‐CM than those with LVEF ≥50% (n = 171: 85 tafamidis‐ and 86 placebo‐treated). At the end of follow‐up (median 60–64 months), all‐cause mortality was numerically higher in patients with baseline LVEF <50%; however, consistent with supportive findings, continuous tafamidis treatment was associated with a 47% reduction in mortality risk compared with delayed tafamidis treatment in patients with LVEF <50% and ≥50% (hazard ratio 0.53 [95% confidence interval 0.367–0.758]; p < 0.001, and 0.53 [0.344–0.818]; p < 0.01, respectively).ConclusionsEarly initiation of tafamidis is associated with reduced mortality in patients with ATTR‐CM, irrespective of initial LVEF value.Clinical Trial Registration: ClinicalTrials.gov NCT01994889, NCT02791230.