Research Update on Loeys-Dietz Syndrome and Marfan syndrome

Dr. Hal Dietz, Victor A. McKusick Professor of Institute of Genetic Medicine and Professor of Pediatrics and Investigator of Howard Hughes Medical Institute at The Johns Hopkins Hospital and Chair of the Loeys-Dietz Syndrome Foundation Medical Advisory Council (MAC), presents “Research Update on Loeys-Dietz Syndrome” at the 2012 LDSF Conference in Baltimore, Maryland, USA. Dr. Dietz discusses the latest on LDS mice model research findings.

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Common blood pressure drug reduces aortic enlargement in Marfan syndrome

marfansyndromeuk1.jpgA common drug that is used to treat high blood pressure in the general population has been found to significantly reduce a dangerous and frequently fatal cardiac problem in patients with Marfan syndrome.

Results of the COMPARE (COzaar in Marfan PAtients Reduces aortic Enlargement) study reveal that patients treated with losartan (Cozaar) had a significantly reduced rate of aortic enlargement after 3 years compared to patients who did not receive the treatment.

“Our study is the first large, prospective randomized study to assess the effects of losartan on aortic enlargement in adults with Marfan syndrome, and confirms previous findings in a mouse model,” said lead investigator Maarten Groenink MD, PhD from the Departments of Cardiology and Radiology at Academic Medical Centre in Amsterdam, The Netherlands.

“We’re very excited to see that such a commonly used drug that is not expensive and has a familiar side-effect profile could have a significant effect on this very serious and frightening risk factor for these patients. These findings may change standard clinical management.”

Marfan syndrome, a heritable connective tissue disorder, affects 2-3 in 10,000 people. It causes progressive enlargement of the aorta, making it prone to rupture, which can be fatal in more than 50% of cases. Currently, the only effective treatment is prophylactic surgical aortic root replacement.

Read More: Yottafire

Learning to Defuse the Aorta

losartanWhen Dr. Hal Dietz arrived at Johns Hopkins University in the 1980s, he became obsessed with helping children with Marfan syndrome, a rare and often fatal disorder that can cause the aorta, the large blood vessel that carries blood from the heart, to grow and grow until it bursts.

“Nothing we were doing seemed to make a difference in their lives,” he said.

These doomed children had a distinctive look that clearly had a genetic basis. They were typically very tall and thin, with long arms, legs and fingers. They often had unusually flexible joints, flat feet and teeth that were crowded in their mouth.

“I decided to study genetics with the sole incentive to identify the gene for Marfan syndrome and ultimately to understand the mechanism,” said Dr. Dietz, now director of the William S. Smilow Center for Marfan Syndrome Research at Johns Hopkins.

That journey has led to surprising discoveries about Marfan’s causes and a soon-to-be published clinical trial of a drug that may help its sufferers.

Dr. Dietz’s work also inspired research that may lead to a blood test that detects enlarged aortas, potentially saving thousands of lives, even among those who do not have Marfan syndrome.

Read More: The New York Times

Common blood pressure drug reduces aortic enlargement in Marfan syndrome – Update

There were no differences in the rate of aortic dissections (0 in the losartan group and 2 controls) or elective aortic surgery (10 in the losartan group and 9 in controls) and no cardiovascular deaths occurred.

marfan syndrome uk logo squareBy European Society of Cardiology, [RxPG] AMSTERDAM, The Netherlands – A common drug that is used to treat high blood pressure in the general population has been found to significantly reduce a dangerous and frequently fatal cardiac problem in patients with Marfan syndrome.

Results of the COMPARE (COzaar in Marfan PAtients Reduces aortic Enlargement) study reveal that patients treated with losartan (Cozaar) had a significantly reduced rate of aortic enlargement after 3 years compared to patients who did not receive the treatment.

Our study is the first large, prospective randomized study to assess the effects of losartan on aortic enlargement in adults with Marfan syndrome, and confirms previous findings in a mouse model, said lead investigator Maarten Groenink MD, PhD from the Departments of Cardiology and Radiology at Academic Medical Centre in Amsterdam, The Netherlands.

We’re very excited to see that such a commonly used drug that is not expensive and has a familiar side-effect profile could have a significant effect on this very serious and frightening risk factor for these patients. These findings may change standard clinical management.

Marfan syndrome, a heritable connective tissue disorder, affects 2-3 in 10,000 people. It causes progressive enlargement of the aorta, making it prone to rupture, which can be fatal in more than 50% of cases. Currently, the only effective treatment is prophylactic surgical aortic root replacement.

In addition to lowering blood pressure, the main benefit of losartan is believed to be its interference with the biochemical process that causes aortic enlargement.

To assess this, the COMPARE study included 233 participants (47% female) with Marfan syndrome from all four academic Marfan screening centers in the Netherlands.

Subjects were a mean age of 41 years, 27% had previously undergone prophylactic aortic root replacement, and the majority (73%) were being treated with beta blockers.

A total of 117 subjects were randomized to receive no further treatment, while 116 were randomized to receive losartan 50 mg daily, doubling after 14 days if there were no side effects.

Aortic enlargement was monitored with magnetic resonance imaging (MRI) for three years of follow-up.

During the study period, if patients in either arm required prophylactic aortic root replacement the decision was left to the discretion of the attending cardiologists based on existing guidelines and anticoagulation therapy was initiated when appropriate.

The study showed that after 3 years aortic root enlargement was significantly less in the losartan group than in controls (0.77 mm vs. 1.35 mm, p=0.014), and 50% of losartan patients showed no growth of the aortic root compared to 31% of controls (p=0.022).

Read More: rxpg news

Losartan shown effective in Marfan syndrome

losartanAMSTERDAM – Daily losartan significantly slowed the aortic root dilatation rate in adults with Marfan syndrome in a 3-year randomized clinical trial.

“I think we can be positive about this treatment. We can now recommend losartan in clinical practice,” Dr. Maarten Groenink said at the annual congress of the European Society of Cardiology.

The COMPARE (Cozaar in Marfan Patients Reduces Aortic Enlargement) trial included 218 patients at all four university Marfan centres in the Netherlands. Patients were randomized to oral losartan at a target dose of 100 mg/day or no losartan in addition to standard-of-care treatment with beta-blockers. Roughly half of the patients in the losartan group were unable to tolerate the full dose of losartan in addition to a beta-blocker; those patients were maintained on losartan at 50 mg/day. Aortic root diameter was measured by MRI at enrollment and after 3 years of prospective follow-up. The aortic dilatation rate was significantly lower in the losartan group than in controls both in the patients with a native root and in those who had undergone aortic root replacement surgery, reported Dr. Groenink, a cardiologist at the Academic Medical Centre, Amsterdam.

Read More: Family Practice News

Common blood pressure drug reduces aortic enlargement in Marfan syndrome

marfan-syndrome-uk-logo-square150AMSTERDAM, The Netherlands – A common drug that is used to treat high blood pressure in the general population has been found to significantly reduce a dangerous and frequently fatal cardiac problem in patients with Marfan syndrome.

Results of the COMPARE (COzaar in Marfan PAtients Reduces aortic Enlargement) study reveal that patients treated with losartan (Cozaar) had a significantly reduced rate of aortic enlargement after 3 years compared to patients who did not receive the treatment.

“Our study is the first large, prospective randomized study to assess the effects of losartan on aortic enlargement in adults with Marfan syndrome, and confirms previous findings in a mouse model,” said lead investigator Maarten Groenink MD, PhD from the Departments of Cardiology and Radiology at Academic Medical Centre in Amsterdam, The Netherlands.

“We’re very excited to see that such a commonly used drug that is not expensive and has a familiar side-effect profile could have a significant effect on this very serious and frightening risk factor for these patients. These findings may change standard clinical management.”

Marfan syndrome, a heritable connective tissue disorder, affects 2-3 in 10,000 people. It causes progressive enlargement of the aorta, making it prone to rupture, which can be fatal in more than 50% of cases. Currently, the only effective treatment is prophylactic surgical aortic root replacement.

In addition to lowering blood pressure, the main benefit of losartan is believed to be its interference with the biochemical process that causes aortic enlargement.

To assess this, the COMPARE study included 233 participants (47% female) with Marfan syndrome from all four academic Marfan screening centers in the Netherlands.

Read More: Science Codex