Drachman, BrianDamy, ThibaudHanna, MazenWang, RonnieAngeli, Franca S.Garcia-Pavia, Pablo2026-01-282026-01-282024-09Drachman, B, Damy, T, Hanna, M, Wang, R, Angeli, F S & Garcia-Pavia, P 2024, 'Long-term tafamidis efficacy in patients with transthyretin amyloid cardiomyopathy by baseline left ventricular ejection fraction', European Journal of Heart Failure, vol. 26, no. 9, pp. 2038-2046. https://doi.org/10.1002/ejhf.33301388-9842https://hdl.handle.net/10641/7735Publisher Copyright: © 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.Aims: Patients 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 results: Patients 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). Conclusions: Early initiation of tafamidis is associated with reduced mortality in patients with ATTR-CM, irrespective of initial LVEF value. Clinical Trial Registration: ClinicalTrials.gov NCT01994889, NCT02791230.91595722enginfo:eu-repo/semantics/openAccess6-min walk testHeart failureMildly reduced ejection fractionPreserved ejection fractionQuality of lifeReduced ejection fractionCardiology and Cardiovascular MedicineJournal ArticleRandomized Controlled TrialClinical Trial, Phase IIIMulticenter StudyYesyes/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article10.1002/ejhf.3330https://www.scopus.com/pages/publications/85197274411https://www.scopus.com/pages/publications/85197274411#tab=citedBy