Silvia Oghina1,2,3, Thibaud Damy1,2,3,4,5, Mélanie Bézard1,2,3,4, Mounira Kharoubi1,2,3,4, Arnault Galat1,2,3,4, Elsa Poullot2,6, Soulef Guendouz1,2,3,4, Pascale Fanen2,7, Benoit Funalot2,7, Anissa Moktefi2,6, Jean-Pascal Lefaucheur8,9, Mukedaisi Abulizi10, Jean-François Deux2,3,4,11, Thierry Gendre2,3,12, Vincent Audard2,3,13,14, Khalil El Karoui13,14, Florence Canoui-Poitrine15, Amira Zaroui1,2,16, Emmanuel Itti2,3,10,14, Emmanuel Teiger1,2,3,4, Violaine Planté-Bordeneuve2,3,12. 1. AP-HP (Assistance Publique-Hôpitaux de Paris), Cardiology Department, DHU-ATVB, Henri Mondor University Hospital, Créteil, France. 2. AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France. 3. AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France. 4. Inserm U955, Université Paris-Est Créteil (UPEC), Créteil, France. 5. AP-HP (Assistance Publique-Hôpitaux de Paris), Clinical Investigation Center 1430, Henri Mondor University Hospital, Créteil, France. 6. AP-HP (Assistance Publique-Hôpitaux de Paris), Henri Mondor University Hospital, Pathology Department, Créteil, France. 7. AP-HP (Assistance Publique-Hôpitaux de Paris), Genetics Department, Henri Mondor University Hospital, Créteil, France. 8. EA4391, ENT, Université Paris Est Créteil 8 rue du General Sarrail, Créteil, France. 9. AP-HP (Assistance Publique-Hôpitaux de Paris), Clinical Neurophysiology Unit, Henri Mondor University Hospital, Créteil, France. 10. AP-HP (Assistance Publique-Hôpitaux de Paris), Nuclear Medicine Department, Henri Mondor University Hospital, Créteil, France. 11. AP-HP (Assistance Publique-Hôpitaux de Paris), Radiology Department, Henri Mondor University Hospital, Créteil, France. 12. AP-HP (Assistance Publique-Hôpitaux de Paris), Neurology Department, Henri Mondor University Hospital, Créteil, France. 13. AP-HP (Assistance Publique-Hôpitaux de Paris), Nephrology and Renal Transplantation Department, Henri Mondor University Hospital, Créteil, France. 14. Univsité Paris Est Créteil, Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Institut Mondor de Recherche Biomédicale (IMRB), Créteil, France. 15. AP-HP (Assistance Publique-Hôpitaux de Paris), Public Health Departement, Henri Mondor University Hospital, Créteil, France. 16. CHU la Rabta, Cardiology Department, Jebbari Tunis, Tunisia.
Abstract
AIMS: Hereditary (ATTRv) and wild-type (ATTRwt) transthyretin amyloidosis are severe and fatal systemic diseases, characterised by amyloid fibrillar accumulation principally in the heart or peripheral nerves (or both). Since 2012, tafamidis has been used in France to treat patients with ATTRv with neuropathy (alone or combined with cardiomyopathy). Recently, the Phase III ATTR-ACT trial showed that tafamidis decreased the relative risk of mortality in ATTR amyloidosis with cardiomyopathy. The aims of this study were to assess the clinical characteristics of ATTR amyloidosis in a real-life population in comparison to the population included in the ATTR-ACT trial and to assess the impact of tafamidis treatment on major cardiovascular outcome (MCO)-free survival time without cardiac decompensation, heart transplant, or death. METHODS AND RESULTS: From June 2008 to November 2018, 648 patients with ATTR amyloidosis (423 ATTRwt and 225 ATTRv) consecutively referred to the French Referral Center for cardiac amyloidosis were included. A total of 467 (72%) patients matched the inclusion criteria of the ATTR-ACT trial. For the 631 patients with cardiomyopathy, tafamidis treatment was associated with a longer median MCO-free survival time (n = 98): 1565 (1010-2400) days vs. 771 (686-895) days without treatment (log-rank P < 0.001). This association was confirmed after considering confounding factors (age at inclusion, N-terminal pro-B-type natriuretic peptide and amyloidosis type) with a propensity score (hazard ratio 0.546; P = 0.0132). CONCLUSION: In a large cohort of ATTRwt and ATTRv patients, representative of the inclusion criteria of the ATTR-ACT trial, the present results show an association between tafamidis treatment and a lower occurrence of cardiovascular outcomes in a real-life population.
AIMS: Hereditary (ATTRv) and wild-type (ATTRwt) transthyretin amyloidosis are severe and fatal systemic diseases, characterised by amyloid fibrillar accumulation principally in the heart or peripheral nerves (or both). Since 2012, tafamidis has been used in France to treat patients with ATTRv with neuropathy (alone or combined with cardiomyopathy). Recently, the Phase III ATTR-ACT trial showed that tafamidis decreased the relative risk of mortality in ATTR amyloidosis with cardiomyopathy. The aims of this study were to assess the clinical characteristics of ATTR amyloidosis in a real-life population in comparison to the population included in the ATTR-ACT trial and to assess the impact of tafamidis treatment on major cardiovascular outcome (MCO)-free survival time without cardiac decompensation, heart transplant, or death. METHODS AND RESULTS: From June 2008 to November 2018, 648 patients with ATTR amyloidosis (423 ATTRwt and 225 ATTRv) consecutively referred to the French Referral Center for cardiac amyloidosis were included. A total of 467 (72%) patients matched the inclusion criteria of the ATTR-ACT trial. For the 631 patients with cardiomyopathy, tafamidis treatment was associated with a longer median MCO-free survival time (n = 98): 1565 (1010-2400) days vs. 771 (686-895) days without treatment (log-rank P < 0.001). This association was confirmed after considering confounding factors (age at inclusion, N-terminal pro-B-type natriuretic peptide and amyloidosis type) with a propensity score (hazard ratio 0.546; P = 0.0132). CONCLUSION: In a large cohort of ATTRwt and ATTRv patients, representative of the inclusion criteria of the ATTR-ACT trial, the present results show an association between tafamidis treatment and a lower occurrence of cardiovascular outcomes in a real-life population.
Authors: Svenja Ney; Peter Ihle; Thomas Ruhnke; Christian Günster; Guido Michels; Katharina Seuthe; Martin Hellmich; Roman Pfister Journal: Clin Res Cardiol Date: 2022-10-14 Impact factor: 6.138