Drug shows promise for Marfan patients

A popular blood-pressure medication has shown promise as a therapy for Marfan syndrome, slowing and, in some cases, stopping the enlargement of a major blood vessel that can lead to fatal ruptures, Johns Hopkins researchers reported today.

Although they cautioned that their study was small and the results preliminary, the scientists at Hopkins' School of Medicine say the drug could reduce the need for the open-heart operations that many patients need to stay alive.


"The results are telling me that there is the potential to prevent aortic disease for a lifetime," said Dr. Harry Dietz, the Hopkins geneticist and cardiologist who led the study appearing in today's New England Journal of Medicine. The aorta is the body's largest artery, carrying blood from the heart to other parts of the body.

In a study of 18 patients, the aorta enlarged by an average of half a millimeter a year after the drug, losartan, was given - compared to an average of 3.5 millimeters before.


"Everyone showed some degree of reduction," said Dietz, adding that 10 patients showed no enlargement at all.

Though a much larger trial is under way to compare losartin with conventional therapy, Dietz said he decided to give the drug to a small group of children with severe disease who were not responding to the drugs they were taking. Those children were at grave risk of complications and faced the possibility of numerous heart operations. (Surgeons replace the damaged section of a patient's aorta with a Dacron tube. But as children age, they often need repeated operations to keep up with the aorta's growth.)

Though he called results of the small study "dramatic," Dietz said doctors should not routinely switch patients to losartin until the larger study is complete and its results known. That could be six years away.

"I personally am not telling all my patients that they should switch to losartin," he said. "I think if patients have not responded well to other therapy and are getting into a desperate situation, I might, in consultation with the family, reach the decision that this is worth trying."

Afflicting 40,000 people in the United States, Marfan is an inherited defect of connective tissue that causes people to be unusually tall and lanky and suffer from dislocated lenses and enlarged aortas. Aortic tears and ruptures can be fatal and are the most serious medical complication.

Dr. Josephine Grima, vice president for research at the National Marfan Foundation, said the drug holds great promise but should not become a mainstream treatment until answers emerge from the larger trial.

"Without a controlled trial, we will not be able to determine how effective it is," she said. In that trial, 604 patients between the ages of 6 months and 25 years will receive either losartin or a beta blocker.

For many years, doctors have tried to forestall ruptures with beta blockers - blood-pressure medications that may relieve pressure on the aorta but do nothing to correct the underlying defect. According to Dietz, it remains unclear whether those drugs lower the risk of aortic complications or prevent the need for surgery.


Losartin belongs to a class of medications called angiotensin receptor blockers or ARBs. Though it's also a blood-pressure medication, losartin works differently than beta blockers and appears to attack the underlying defect of Marfan.

In 1991, Hopkins researchers identified the genetic defect that causes the disease - an abnormality in a protein that normally puts brakes on tissue growth. More recently, Dietz's lab found that the drug had the potential in mice "to prevent aneurysms for a lifetime."

In an editorial accompanying today's article in the New England Journal of Medicine, Dr. Reed E. Pyeritz wrote that "the most appropriate course of action for patients with Marfan's syndrome and their physicians is to give serious consideration to enrolling in the trial." Pyeritz is chief of molecular genetics at the University of Pennsylvania School of Medicine.

Some patients, however, may not be eligible for the trial because they have had previous heart surgery or aortic tears. For those, he said, losartin may be "a reasonable choice."