Contemporary Real-World Treatment of Cardiac Transthyretin Amyloidosis with Tafamidis: A Long-Term Multicenter, Observational Study

R. J. Nies (Köln)¹, S. Ney (Köln)², I. Kindermann (Homburg/Saar)³, Y. Bewarder (Homburg/Saar)³, A. Zimmer (Homburg/Saar)³, F. Knebel (Berlin)⁴, K. Hahn (Berlin)⁵, S. Spethmann (Berlin)⁶, P. Lüdike (Osnabrück)⁷, L. Michel (Essen)⁸, T. Rassaf (Essen)⁸, M. Papathanasiou (Frankfurt am Main)⁹, S. Störk (Würzburg)¹⁰, V. Cejka (Würzburg)¹⁰, A. Polzin (Düsseldorf)¹¹, F. Voß (Düsseldorf)¹¹, M. Kelm (Düsseldorf)¹¹, B. Unsöld (Gießen)¹², C. Meindl (Regensburg)¹³, M. Paulus (Regensburg)¹³, A. Yilmaz (Münster)¹⁴, B. Chamling (Greifswald)¹⁵, C. Morbach (Würzburg)¹⁶, R. Pfister (Köln)^2
1Universitätsklinikum Köln Klinik III für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland; ²Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; ³Universitätsklinikum des Saarlandes Innere Medizin III - Kardiologie, Angiologie und internistische Intensivmedizin Homburg/Saar, Deutschland; ⁴Sana Klinikum Lichtenberg Klinik für Innere Medizin II, Schwerpunkt Kardiologie Berlin, Deutschland; ⁵Klinik für Neurologie Amyloidosis Center Charite Berlin Berlin, Deutschland; ⁶Charité - Universitätsmedizin Berlin Klinik für Kardiologie, Angiologie und Intensivmedizin Berlin, Deutschland; ⁷Marienhospital Osnabrück Klinik für Innere Medizin / Kardiologie und Intensivmedizin Osnabrück, Deutschland; ⁸Universitätsklinikum Essen Klinik für Kardiologie und Angiologie Essen, Deutschland; ⁹Universitätsklinikum Frankfurt Med. Klinik III - Kardiologie, Angiologie Frankfurt am Main, Deutschland; ¹⁰Universitätsklinikum Würzburg Deutsches Zentrum für Herzinsuffizienz/DZHI Würzburg, Deutschland; ¹¹Universitätsklinikum Düsseldorf Klinik für Kardiologie, Pneumologie und Angiologie Düsseldorf, Deutschland; ¹²Universitätsklinikum Gießen und Marburg GmbH Medizinische Klinik I - Kardiologie und Angiologie Gießen, Deutschland; ¹³Universitätsklinikum Regensburg Klinik und Poliklinik für Innere Med. II, Kardiologie Regensburg, Deutschland; ¹⁴Universitätsklinikum Münster Herz-MRT-Zentrum Münster, Deutschland; ¹⁵Universitätsmedizin Greifswald Klinik und Poliklinik für Innere Medizin B Greifswald, Deutschland; ¹⁶Universitätsklinikum Würzburg Medizinische Klinik I, Kardiologie Würzburg, Deutschland

Ams: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a severe and progressive disease with several emerging disease-modifying therapies. Tafamidis 61 mg was the first drug approved for ATTR-CM therapy but contemporary real-world evidence on outcomes is lacking.

Methods: This retrospective, multicenter study included patients with ATTR-CM from eight German tertiary care centers enrolled in the first year after approval and commercial availability of tafamidis 61 mg in Europe (April 2020 to March 2021). The primary endpoint was all-cause mortality, and the secondary endpoint was a composite of all-cause mortality and/or heart failure (HF) hospitalization.

Results: A total of 313 patients with median age 79 [76 - 82] years, 85% males and 8% variant ATTR were analyzed of whom 83% (n = 259) were treated with tafamidis 61 mg. During median follow-up of 39 [18 – 48] months, 21% of patients died and 42% experienced a composite endpoint. Patients treated with tafamidis exhibited a 3-year survival of 86% and an event-free survival of 63%. After propensity-score matching for age, NYHA class, NAC stage, and serum albumin, tafamidis was significantly associated with a 72% reduction in all-cause mortality (HR 0.28; 95% confidence interval [CI] 0.13 - 0.61; p = 0.001) and a 44% reduction of the composite endpoint (HR 0.56; 95% CI 0.33 - 0.97; p = 0.039). Survival benefit was consistent in wildtype ATTR-CM patients and those with ATTR-CM diagnoses within the last 12 months. Among tafamidis-treated patients, NAC stage III, age ≥ 80 years, and serum albumin ≤ 42.5 g/L were associated with all-cause mortality, while NYHA class ≥ III, NAC stage ≥ II, age ≥ 80 years, and serum albumin ≤ 42.5 g/L were associated with risk of the composite endpoint.

Conclusions: This study provides data for a benchmark of long-term outcomes of contemporary real-world patients with ATTR-CM treated with tafamidis 61 mg. Low serum albumin, advanced NAC stage, and older age were strong predictors of adverse outcomes, emphasizing the importance of early diagnosis and timely therapy of ATTR-CM.