Olivier Milleron1, Florence Arnoult2, Jacques Ropers3, Philippe Aegerter4, Delphine Detaint1, Gabriel Delorme5, David Attias5, Florence Tubach6, Sophie Dupuis-Girod7, Henry Plauchu7, Martine Barthelet8, Francois Sassolas8, Nicolas Pangaud8, Sophie Naudion9, Julie Thomas-Chabaneix10, Yves Dulac11, Thomas Edouard11, Jean-Eric Wolf12, Laurence Faivre12, Sylvie Odent13, Adeline Basquin14, Gilbert Habib15, Patrick Collignon15, Catherine Boileau16, Guillaume Jondeau17. 1. Centre National de Référence pour le syndrome de Marfan et apparentés, Hôpital Bichat, 46 rue Henry Huchard, Paris 75018, France Service de Cardiologie, AP-HP, Hôpital Bichat, Paris, France. 2. Centre National de Référence pour le syndrome de Marfan et apparentés, Hôpital Bichat, 46 rue Henry Huchard, Paris 75018, France Service d'explorations fonctionnelles, AP-HP, Hôpital Bichat, Paris, France. 3. Unité de Recherche Clinique HU Paris Île-de-France Ouest, AP-HP, Hôpital Ambroise Paré, Boulogne, France. 4. Unité de Recherche Clinique HU Paris Île-de-France Ouest, AP-HP, Hôpital Ambroise Paré, Boulogne, France Université Versailles St-Quentin, Paris EA2506, France. 5. Centre National de Référence pour le syndrome de Marfan et apparentés, Hôpital Bichat, 46 rue Henry Huchard, Paris 75018, France. 6. AP-HP, Hôpital Bichat, Biostatistique et Recherche Clinique, Paris, France INSERM, Paris U738, France Université Denis Diderot Paris VII, 75013 Paris, France. 7. Service de Génétique, Hôpital Hôtel-Dieu, Lyon, France. 8. Service de Cardiologie, Lyon, France. 9. Service de Génétique, CHU Bordeaux, Bordeaux, France. 10. Service des Maladies Cardio-vasculaires Congénitales, CHU Bordeaux, Bordeaux, France. 11. CHU Toulouse, Toulouse, France. 12. CHU Dijon, Dijon, France. 13. Service de Génétique Clinique, CHU Hôpital sud, Université de Rennes 1, Rennes, France. 14. service de Cardiologie, CHU Hôpital Pontchaillou, Rennes, France. 15. CHU Marseille, Marseille, France. 16. Centre National de Référence pour le syndrome de Marfan et apparentés, Hôpital Bichat, 46 rue Henry Huchard, Paris 75018, France Université Denis Diderot Paris VII, 75013 Paris, France INSERM LVTS U1148, Paris 75018, France Département de Génétique, AP-HP, Hôpital Bichat, Paris, France. 17. Centre National de Référence pour le syndrome de Marfan et apparentés, Hôpital Bichat, 46 rue Henry Huchard, Paris 75018, France Service de Cardiologie, AP-HP, Hôpital Bichat, Paris, France INSERM LVTS U1148, Paris 75018, France guillaume.jondeau@bch.aphp.fr.
Abstract
AIMS: To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS). METHODS AND RESULTS: A double-blind, randomized, multi-centre, placebo-controlled, add on trial comparing Losartan (50 mg when <50 kg, 100 mg otherwise) vs. placebo in patients with MFS according to Ghent criteria, age >10 years old, and receiving standard therapy. 303 patients, mean age 29.9 years old, were randomized. The two groups were similar at baseline, 86% receiving β-blocker therapy. The median follow-up was 3.5 years. The evolution of aortic diameter at the level of the sinuses of Valsalva was not modified by the adjunction of Losartan, with a mean increase in aortic diameter at the level of the sinuses of Valsalva of 0.44 mm/year (s.e. = 0.07) (-0.043 z/year, s.e. = 0.04) in patients receiving Losartan and 0.51 mm/year (s.e. = 0.06) (-0.01 z/year, s.e. = 0.03) in those receiving placebo (P = 0.36 for the comparison on slopes in millimeter per year and P = 0.69 for the comparison on slopes on z-scores). Patients receiving Losartan had a slight but significant decrease in systolic and diastolic blood pressure throughout the study (5 mmHg). During the study period, aortic surgery was performed in 28 patients (15Losartan, 13 placebo), death occurred in 3 patients [0 Losartan, 3 placebo, sudden death (1) suicide (1) oesophagus cancer (1)]. CONCLUSION:Losartan was able to decrease blood pressure in patients with MFS but not to limit aortic dilatation during a 3-year period in patients >10 years old. β-Blocker therapy alone should therefore remain the standard first line therapy in these patients. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS). METHODS AND RESULTS: A double-blind, randomized, multi-centre, placebo-controlled, add on trial comparing Losartan (50 mg when <50 kg, 100 mg otherwise) vs. placebo in patients with MFS according to Ghent criteria, age >10 years old, and receiving standard therapy. 303 patients, mean age 29.9 years old, were randomized. The two groups were similar at baseline, 86% receiving β-blocker therapy. The median follow-up was 3.5 years. The evolution of aortic diameter at the level of the sinuses of Valsalva was not modified by the adjunction of Losartan, with a mean increase in aortic diameter at the level of the sinuses of Valsalva of 0.44 mm/year (s.e. = 0.07) (-0.043 z/year, s.e. = 0.04) in patients receiving Losartan and 0.51 mm/year (s.e. = 0.06) (-0.01 z/year, s.e. = 0.03) in those receiving placebo (P = 0.36 for the comparison on slopes in millimeter per year and P = 0.69 for the comparison on slopes on z-scores). Patients receiving Losartan had a slight but significant decrease in systolic and diastolic blood pressure throughout the study (5 mmHg). During the study period, aortic surgery was performed in 28 patients (15 Losartan, 13 placebo), death occurred in 3 patients [0 Losartan, 3 placebo, sudden death (1) suicide (1) oesophagus cancer (1)]. CONCLUSION:Losartan was able to decrease blood pressure in patients with MFS but not to limit aortic dilatation during a 3-year period in patients >10 years old. β-Blocker therapy alone should therefore remain the standard first line therapy in these patients. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Sherene Shalhub; Peter H Byers; Kelli L Hicks; Dawn M Coleman; Frank M Davis; Giovanni De Caridi; K Nicole Weaver; Erin M Miller; Marc L Schermerhorn; Katie Shean; Gustavo Oderich; Mauricio Ribeiro; Cole Nishikawa; Kristofer Charlton-Ouw; Christian-Alexander Behrendt; E Sebastian Debus; Yskert von Kodolitsch; Devin Zarkowsky; Richard J Powell; Melanie Pepin; Dianna M Milewicz; Ellen S Regalado; Peter F Lawrence; Karen Woo Journal: J Vasc Surg Date: 2019-07-26 Impact factor: 4.268
Authors: Jorge Oller; Nerea Méndez-Barbero; E Josue Ruiz; Silvia Villahoz; Marjolijn Renard; Lizet I Canelas; Ana M Briones; Rut Alberca; Noelia Lozano-Vidal; María A Hurlé; Dianna Milewicz; Arturo Evangelista; Mercedes Salaices; J Francisco Nistal; Luis Jesús Jiménez-Borreguero; Julie De Backer; Miguel R Campanero; Juan Miguel Redondo Journal: Nat Med Date: 2017-01-09 Impact factor: 53.440