Marfan Sartan: a randomized, double-blind, placebo-controlled trial.
OBJECTIVE
To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS).


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)].


CONCLUSIONS
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.
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.
Olivier
O
Milleron
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.
Florence
F
Arnoult
Unité de Recherche Clinique HU Paris Île-de-France Ouest, AP-HP, Hôpital Ambroise Paré, Boulogne, France.
Jacques
J
Ropers
Unité de Recherche Clinique HU Paris Île-de-France Ouest, AP-HP, Hôpital Ambroise Paré, Boulogne, France Université Versailles St-Quentin, Paris EA2506, France.
Philippe
P
Aegerter
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.
Delphine
D
Detaint
Centre National de Référence pour le syndrome de Marfan et apparentés, Hôpital Bichat, 46 rue Henry Huchard, Paris 75018, France.
Gabriel
G
Delorme
Centre National de Référence pour le syndrome de Marfan et apparentés, Hôpital Bichat, 46 rue Henry Huchard, Paris 75018, France.
David
D
Attias
AP-HP, Hôpital Bichat, Biostatistique et Recherche Clinique, Paris, France INSERM, Paris U738, France Université Denis Diderot Paris VII, 75013 Paris, France.
Florence
F
Tubach
Service de Génétique, Hôpital Hôtel-Dieu, Lyon, France.
Sophie
S
Dupuis-Girod
Service de Génétique, Hôpital Hôtel-Dieu, Lyon, France.
Henry
H
Plauchu
Service de Cardiologie, Lyon, France.
Martine
M
Barthelet
Service de Cardiologie, Lyon, France.
Francois
F
Sassolas
Service de Cardiologie, Lyon, France.
Nicolas
N
Pangaud
Service de Génétique, CHU Bordeaux, Bordeaux, France.
Sophie
S
Naudion
Service des Maladies Cardio-vasculaires Congénitales, CHU Bordeaux, Bordeaux, France.
Julie
J
Thomas-Chabaneix
CHU Toulouse, Toulouse, France.
Yves
Y
Dulac
CHU Toulouse, Toulouse, France.
Thomas
T
Edouard
CHU Dijon, Dijon, France.
Jean-Eric
JE
Wolf
CHU Dijon, Dijon, France.
Laurence
L
Faivre
Service de Génétique Clinique, CHU Hôpital sud, Université de Rennes 1, Rennes, France.
Sylvie
S
Odent
service de Cardiologie, CHU Hôpital Pontchaillou, Rennes, France.
Adeline
A
Basquin
CHU Marseille, Marseille, France.
Gilbert
G
Habib
CHU Marseille, Marseille, France.
Patrick
P
Collignon
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.
Catherine
C
Boileau
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.
Guillaume
G
Jondeau
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001018:Aortic Diseases / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D001794:Blood Pressure / Q000187:drug effects; D004108:Dilatation, Pathologic / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000517:prevention & control; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008382:Marfan Syndrome / Q000150:complications* / Q000401:mortality; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan
Aorta; Echocardiography; Marfan; Sartan