Teams from the Cochin, Hôtel-Dieu and Necker-Enfants Malades AP-HP hospitals, the University of Paris and Inserm, in collaboration with the North/East/Ile-de-France reference center for neuromuscular diseases, with the support of the Monegasque association against myopathies, carried out work on the impact of early preventive treatment with angiotensin-converting enzyme inhibitors (ACEi) in Duchenne muscular dystrophy. The results of this work show that this early preventive treatment for patients 8 years or older with Duchenne muscular dystrophy is associated with significantly higher overall survival and lower hospitalization rates for patients treated. The results of this work were published on March 22, 2021, in the European Heart Journal.

Duchenne muscular dystrophy is a serious genetic disorder caused by the lack of an essential support protein for muscle contraction, dystrophin. It causes muscle and myocardial damage and does not have any current specific curative treatment. The approach developed in the work published in the European Heart Journal is the first to demonstrate an unquestionable reduction in mortality, very significant especially in cardiovascular mortality , thanks to this early treatment.

The patients included in this retrospective study were identified among the 668 patients registered in the “DMD-Heart-Registry”. This register, coordinated by Pr Wahbi, includes patients admitted between January 1986 and October 2018 in eight French medical centers for the management of Duchenne muscular dystrophy. More than 600 children were included in this retrospective work and the team in charge of this work observed a reduction in mortality estimated, after 12 years of follow-up, at more than 50%. A first pilot study conducted in 2007 on 60 children coordinated within the cardiology department of Cochin AP-HP hospital (Pr Duboc, Pr Meune, Dr Bécane, Pr Wahbi) already indicated the potential benefit of such a treatment. Today it is a larger, multicenter national study involving several hundred patients affected by this orphan disease, which confirms the initial results.

Three main structures within AP-HP have largely contributed to the outcome of this work: the constitutive rare diseases reference center for cardiac myopathies (Pr Wahbi, Pr D. Duboc) within the cardiology service of the Cochin AP-HP hospital which coordinated this work, helped by the neuro-pediatrics department of the Necker-Enfants malades AP-HP hospital (Pr Desguerre) which allowed the bio-statistical analysis of the results which was carried out by the clinical epidemiology center of Hôtel-Dieu AP-HP (Pr Porcher, Pr Ravaud).

The practical conclusion of this study shows that this early preventive angiotensin-converting enzyme inhibitors (ACEi) therapy for patients 8 years of age or older with Duchenne muscular dystrophy is associated with significantly higher overall survival and lower heart failure hospitalization rate for patients in care.

Reference :

Association between Pharmacological Angiotensin Converting Enzyme Inhibition and Overall Survival in Duchenne Muscular Dystrophy (Analysis of Registry Data) : Raphaël Porcher, PhD, Isabelle Desguerre, MD, PhD, Helge Amthor, MD, PhD, Brigitte Chabrol, MD, PhD, Frédérique Audic, MD, François Rivier, MD, PhD, Arnaud Isapof, MD, Vincent Tiffreau, MD, PhD, Emmanuelle Campana-Salort, MD, France Leturcq, MD, Sylvie Tuffery-Giraud, MD, Rabah Ben Yaou, MD, Djillali Annane, MD, PhD, Pascal Amédro, MD, PhD, Christine Barnerias, MD, Henri Marc Bécane, MD, Anthony Béhin, MD, Damien Bonnet, MD, PhD, Guillaume Bassez, MD, PhD, Mireille Cossée, MD, Grégoire de La Villéon, MD, Claire Delcourte, MD, Abdallah Fayssoil, MD, PhD, Bertand Fontaine, MD, PhD, François Godart, MD, PhD, Sophie Guillaumont, MD, Emmanuelle Jaillette, MD, Pascal Laforêt, MD, PhD, Sarah Leonard-Louis, MD, Frederic Lofaso, MD, PhD, Michele Mayer, MD, Raul Juntas Morales, MD, Christophe Meune, MD, PhD, David Orlikowski, MD, PhD, Caroline Ovaert, MD, PhD, Hélène Prigent, MD, PhD, Malika Saadi, MD, Maximilien Sochala, MD, Celine Tard, MD, Guy Vaksmann, MD, Ulrike Walther-Louvier, MD, Bruno Eymard, MD, PhD, Tanya Stojkovic, MD, Philippe Ravaud, MD, PhD, Denis Duboc, MD, PhD, Karim Wahbi, MD, PhD. European Heart Journal.

DOI: https://doi.org/10.1093/eurheartj/ehab054