Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial.

نویسندگان

  • Maarten Groenink
  • Alexander W den Hartog
  • Romy Franken
  • Teodora Radonic
  • Vivian de Waard
  • Janneke Timmermans
  • Arthur J Scholte
  • Maarten P van den Berg
  • Anje M Spijkerboer
  • Henk A Marquering
  • Aeilko H Zwinderman
  • Barbara J M Mulder
چکیده

AIM Patients with Marfan syndrome have an increased risk of life-threatening aortic complications, mostly preceded by aortic dilatation. Treatment with losartan, an angiotensin-II receptor-1 blocker, may reduce aortic dilatation rate in Marfan patients. METHODS AND RESULTS In this multicentre, open-label, randomized controlled trial with blinded assessments, we compared losartan treatment with no additional treatment in operated and unoperated adults with Marfan syndrome. The primary endpoint was aortic dilatation rate at any predefined aortic level after 3 years of follow-up, as determined by magnetic resonance imaging. A total of 233 participants (47% female) underwent randomization to either losartan (n = 116) or no additional treatment (n = 117). Aortic root dilatation rate after 3.1 ± 0.4 years of follow-up was significantly lower in the losartan group than in controls (0.77 ± 1.36 vs. 1.35 ± 1.55 mm, P = 0.014). Aortic dilatation rate in the trajectory beyond the aortic root was not significantly reduced by losartan. In patients with prior aortic root replacement, aortic arch dilatation rate was significantly lower in the losartan group when compared with the control group (0.50 ± 1.26 vs. 1.01 ± 1.31 mm, P = 0.033). No significant differences in separate clinical endpoints or the composite endpoint (aortic dissection, elective aortic surgery, cardiovascular death) between the groups could be demonstrated. CONCLUSION In adult Marfan patients, losartan treatment reduces aortic root dilatation rate. After aortic root replacement, losartan treatment reduces dilatation rate of the aortic arch.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE trial

BACKGROUND Marfan syndrome (MFS) is one of the most common systemic disorders of connective tissue with the incidence of approximately 2-3 per 10 000 individuals. Aortic disease, leading to progressive aneurysmal dilatation and dissection is the main cause of morbidity and mortality of Marfan patients. Current treatment (e.g. beta blockers and elective surgery) does postpone but cannot prevent ...

متن کامل

Beneficial Outcome of Losartan Therapy Depends on Type of FBN1 Mutation in Marfan Syndrome.

BACKGROUND It has been shown that losartan reduces aortic dilatation in patients with Marfan syndrome. However, treatment response is highly variable. This study investigates losartan effectiveness in genetically classified subgroups. METHODS AND RESULTS In this predefined substudy of COMPARE, Marfan patients were randomized to daily receive losartan 100 mg or no losartan. Aortic root dimensi...

متن کامل

Rationale and design of a randomized clinical trial (Marfan Sartan) of angiotensin II receptor blocker therapy versus placebo in individuals with Marfan syndrome.

BACKGROUND Recent studies have demonstrated that blockade of the angiotensin II type 1 receptor with losartan decreases aortic damage in an animal model of Marfan syndrome (a KI mouse model with a pathogenic mutation in the gene coding for fibrillin-1). AIMS To demonstrate a beneficial effect of losartan on aortic dilatation when added to optimal therapy in patients with Marfan syndrome. ME...

متن کامل

COMPARE and Pediatric Heart Network Investigator trials: Losartan finally validated in humans with Marfan, but much work remains!

A landmark study by Habashi et al(1) in 2006 documented for the first time both the prevention and reversal of structural changes in the aorta associated with Marfan syndrome, via pharmacological means. This study, carried out in a rat model, concluded that such results were due to an inhibitor effect by the drug losartan on TGB-β1 (Figure 1). Habashi's paper prompted some physicians, in the ab...

متن کامل

Losartan treatment in adult patients with Marfan syndrome: can we finally COMPARE?

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with a prevalence of 1 in 5000 individuals. The syndrome results from mutations in the fibrillin-1-encoding gene (FBN1). As .600 mutations in FBN1 have been reported, a great variety of phenotypes are encountered. Hence, MFS is a systemic disorder which may differently affect the cardiovascular, ocular, and musculoskeleta...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • European heart journal

دوره 34 45  شماره 

صفحات  -

تاریخ انتشار 2013