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Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE
Teodora Radonic1, Piet de Witte, Marieke J H Baars
1Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center Amsterdam, the Netherlands. t.radonic@amc.nl
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 aortic complications in these patients. Recent studies have found transforming growth factor beta (TGF beta) to be involved in the aortic aneurysm formation. Losartan, an angiotensin II type 1 receptor blocker inhibits TGFbeta in a mouse model of Marfan syndrome leading to inhibition of aortic growth. The main objective of this trial is to assess whether losartan treatment leads to a clinically relevant decrease of aortic dilatation in adult patients with Marfan syndrome.
Methods/Design:
COMPARE study (COzaar in Marfan Patients Reduces aortic Enlargement) is an open-label, randomized, controlled trial with blinded end-points. Treatment with losartan will be compared with no additional treatment after 3 years of follow-up. We will enroll 330 patients with MFS who will be randomly assigned to receive losartan or not. Patients taking beta-blockers will continue taking their standard treatment. The primary end-point is the largest change in aortic diameter at any aortic level measured by means of MRI. Secondary end-points are change in mortality, incidence of dissection, elective aortic surgery, aortic volume, aortic stiffness and ventricular function. We will also investigate gene and protein expression change in the skin under losartan therapy and create prediction models for losartan-treatment response and aortic dilatation.
Discussion:
The COMPARE study will provide important evidence of effects of losartan treatment in adult Marfan patient population. We expect losartan to significantly reduce the occurrence and progression of aortic dilatation. This trial investigates a wide spectrum of clinical, genetic and biochemical effects of losartan aiming to provide further insight in the pathogenesis and treatment of Marfan syndrome.
Trial Registration:
Netherlands Trial Register NTR1423.
Insights
Losartan treatment may reduce aortic dilatation in Marfan syndrome patients. This study investigates losartan
Area of Science:
- Cardiovascular Medicine
- Genetics
- Pharmacology
Background:
- Marfan syndrome (MFS) is a genetic connective tissue disorder affecting approximately 2-3 per 10,000 individuals.
- Aortic complications, including aneurysmal dilatation and dissection, are the primary cause of mortality in MFS patients.
- Current treatments delay but do not prevent aortic disease progression.
Purpose of the Study:
- To assess the efficacy of losartan in reducing aortic dilatation in adult Marfan syndrome patients.
- To investigate the clinical, genetic, and biochemical effects of losartan therapy in MFS.
- To explore prediction models for treatment response and aortic dilatation.
Main Methods:
- The COMPARE study is an open-label, randomized, controlled trial with blinded endpoints.
- 330 MFS patients will be randomized to receive losartan or no additional treatment over 3 years.
- The primary endpoint is the change in aortic diameter measured by MRI; secondary endpoints include mortality, dissection, surgery, and ventricular function.
Main Results:
- This section is not available in the provided abstract.
- Further analysis is required to determine the study's main results.
Conclusions:
- The COMPARE study is expected to provide significant evidence on losartan's effect on aortic dilatation in MFS.
- Losartan is anticipated to reduce the occurrence and progression of aortic dilatation.
- The trial aims to enhance understanding of MFS pathogenesis and treatment strategies.
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