Losartan Questions and Answers
Hope and optimism resonated throughout the NMF’s 2007 Annual Conference, and the buzz increased after Dr. Hal Dietz presented his recently published data about the impact of losartan, an FDA-approved medication, on mice with Marfan syndrome. The data, which were published in Science April 7, 2007, showed that losartan stops aortic enlargement and potentially reverses existing aortic root growth in Marfan mice.
At the NMF conference, Dr. Dietz described how losartan might help the connective tissue in the aorta and have other effects on Marfan syndrome features, specifically on the problems related to the lungs and muscle mass.
Conference participants had many questions about the clinical trial that Dr. Dietz answered during a one-hour question and answer session. Here are the highlights.
WILL LOSARTAN CURE MARFAN SYNDROME?
This is our hope, but it is not likely. Rather, if the clinical trial results are positive, Marfan syndrome as we know it will be changed forever. As when aortic surgery was developed, there will be a much more optimistic outlook for those affected.
DOES LOSARTAN HAVE ANY EFFECT ON THE SKELETAL PROBLEMS OR EYE PROBLEMS ASSOCIATED WITH MARFAN SYNDROME?
Losartan may have some effect, but we don’t have the answers yet. We hope that studies ancillary to the core clinical trial can be funded by the National Marfan Foundation to determine any benefits of losartan on other body systems.
WILL LOSARTAN HAVE AN IMPACT ON DURAL ECTASIA?
It is known that, like aortic dilation, dural ectasia is related to too much TGFbeta. Research has not yet been conducted on mice to look at this but, theoretically, losartan might address dural ectasia too.
WHAT CLASS OF DRUG IS LOSARTAN? WILL OTHER DRUGS IN THE CLASS HAVE THE SAME EFFECT?
Losartan is in a class of drugs known as angiotensin receptor blockers (ARB). Of all the drugs in that class, losartan has the longest history and the most data on blocking TGFbeta. Other drugs in the class are likely to have the same impact, but we focused on losartan because of its record of safety and efficacy.
DOES LOSARTAN HAVE THE SAME SIDE EFFECTS AS BETA-BLOCKERS?
In some people, beta-blockers make depression and asthma worse. Losartan is not known to have these side effects and is known to be well-tolerated by the general public. There is no reason to believe that it will cause depression, hyperactivity or pain.
IS THERE ANY OVERSIGHT TO THE STUDY TO ENSURE THAT IT IS SAFE FOR ALL PARTICIPANTS?
A Data Monitoring Safety Board will oversee the clinical trial. This group was selected by the National Heart, Lung and Blood Institute to provide oversight due to their training and expertise in cardiology studies and echocardiography interpretation.
WHY IS THERE AN UPPER AGE LIMIT FOR STUDY PARTICIPANTS?
The clinical trial was designed to obtain the answers about losartan as quickly as possible. The age range was selected based on an age group that is most likely to experience aortic growth during a three-year period (the length of the study). Therefore, the study guidelines limit participants to those in a period of most active growth.
WHAT DOSAGES OF LOSARTAN WERE GIVEN TO MICE IN THE STUDY? WHAT DOSAGE WILL BE GIVEN TO PEOPLE IN THE CLINICAL TRIAL?
In the mice study, we did not use extreme dosing of losartan to get a result. Typical dosing to lower blood pressure was given to the mice. Virtually all mice showed the same effects with losartan. Typical dosing for body weight and age will also be used for people with Marfan syndrome in the clinical trial.
HOW DO CLINICAL TRIAL PARTICIPANTS OBTAIN THEIR MEDICATION?
The study centers will provide the medication. Study participants will not know if they are taking losartan or beta-blockers.
IF THE STUDY IS DOUBLE- BLIND HOW ARE PRESCRIPTIONS GIVEN OUT AND DOSAGES CHANGED, AS NEEDED, FOR STUDY PARTICIPANTS?
Each study center has a coordinator who will be responsible for the prescriptions and dosages. The same system will be in place at each study site to ensure that this information is kept from all physicians, researchers and patients to maintain the integrity of the study.
WAS THERE ANY CONSIDERATION FOR THE STUDY TO INCLUDE PARTICIPANTS WHO WOULD TAKE BETA-BLOCKERS AND LOSARTN TOGETHER?
In the research on mice, some mice received both losartan and beta-blockers, while some mice received losartan only and others received beta-blockers only. The mice on losartan alone were seen to have the full benefit, equal to the combination therapy group. It is much preferred that the clinical trial in people focus on a single therapy.
CAN LOSARTAN BE TAKEN DURING PREGNANCY?
Losartan cannot be taken during pregnancy. The drug influences kidney development in the developing fetus and is related to an increased risk of fetal loss.
WERE MICE TREATED WITH LOSARTAN FROM BIRTH? WERE ANY TREATED LATER IN THEIR LIVES?
In the initial experiment, mice were treated with losartan beginning at birth. In subsequent experiments, mice were treated at two months of age (equivalent to a human who is a teenager). These mice already had experienced aortic growth. Both groups showed positive results with losartan.
IS THERE A CHANCE THAT THE STUDY COULD BE STOPPED EARLY?
The study could be stopped early based on the magnitude of the effect of the drug. Results will be examined periodically by the Data Monitoring Safety Board. If the people on losartan show a dramatic effect, as opposed to people on the beta-blocker, then the study will be stopped and all participants put on losartan.
IF LOSARTAN DOES WORK IN PEOPLE WITH MARFAN SYNDROME, WILL THE MEDICATION NEED TO BE TAKEN FOR LIFE?
We anticipate that long-term (life-long) use of losartan will be recommended, but we need experience with people first. In the future, we can conduct more experiments with mice to determine if losartan will be needed for long-term or short-term usage.
HOW WILL THE STUDY BE FUNDED? WILL ANY PHARMACEUTICAL FUNDING BE USED?
The trial will be funded by the National Institutes of Health (NIH) through the National Heart, Lung and Blood Institute (NHLBI). The NMF is working to raise funds to support ancillary studies that will study the effects of losartan on other complications of Marfan syndrome.
Funding from pharmaceutical companies is welcome. Strict guidelines are in place so that pharmaceutical companies cannot influence the outcome of the studies.
WHAT IF I OR MY CHILD IS NOT ELIGIBLE FOR THE CLINICAL TRIAL? SINCE LOSARTAN IS AVAILABLE ON THE MARKET, CAN MY DOCTOR SIMPLY PRESCRIBE IT FOR BLOOD PRESSURE CONTROL?
If you are not eligible for the trial, you should have a conversation with your doctor. As with starting any new medication, discuss with your doctor the risks and benefits. We do not advocate switching from a beta blocker to losartan until the trial is completed.