Effectiveness of losartan

[nickppatel]

Hi, and thanks for taking my question. I have a dilated aortic root and ascending aorta, about 3.8cm and 3.4cm, respectively. I've been taking 40mg/day Diovan/valsartan recently in addition to beta blockers. I've heard about studies and reports that ARBs such as losartan and valsartan have proven effective in mice to treat aortic aneurysms in Marfan mice and to effectivel 'heal' them.

1.) So this is a general question - in your practice, have you seen beneficial results on human aortic aneurysms using ARBs?

2.) To the extent that you might know, is my dose of 40mg/day for a 180 lb, 6'1" man too light to have an effect?

Thanks!

[Schmoomcgoo]

Best of luck to you.

[nickppatel]

According to Dr Dietz's report, this therapy may be helpful with non-MFS related aortic problems such as yours. You might discuss it with your cardiologist.

Unfortunately, I do not think you'd be a candidate for the study. I believe the study is restricted to MFS patients 25 yrs old and under. I do not qualify either, since I technically do not meet the criteria for MFS, and because by the time the study begins, I will be 26.

I am taking valsartan and we'll see how it goes. Although I am taking a light dose, I have read studies which indicate that the affinity of Valsartan for the AT1 receptors is 5x that of losartan. Blocking AT1 receptors, I believe, inhibits TGF-beta signaling, which is the goal with this medication. We'll see what happens ...

[Schmoomcgoo]

This is an EXCELLENT question!  Perhaps we should re-state it as "Is it reasonable to add an ARB to the blood pressure control regimen of one with an aortic aneurysm?" or "Does adding an ARB to the medicinal treatment of one with an aortic aneurysm fall into the 'can't hurt, might help' category?"  I intend to ask my cardiologist to do just that...or give me a good reason why not.  Beta blockers and ace inhibitors have been shown to control blood pressure and slow development of aortic aneurysms in humans, but have the effects of ARB's on human aortas been studied?  They are already used, so how could they hurt?  Might they have the same effect in humans as in mice?  Worth a shot?  Why not?

[Schmoomcgoo]

I do not have MFS (confirmed by genetic testing--no Fbn1 mutation), but I do have BAV and a 4.5cm aneurysm.  I read the synopsis of the study on a Johns Hopkins website and it sounds like the ARB works by inhibiting the expression of a specific biochemical process that takes place in the tissue of MFS aortas.  I would be curious to know if a similar process takes place in BAV aortas. The MFS lists BAV as a related disorder and I am unclear on whether that's because the two share clinical symptoms (i.e. aneurysms and valve problems) or if there is a genetic connection I am unaware of.  I wouldn't mind participating in the study if I was deemed a candidate.

[nickppatel]

I'm actually helping Dr Hal Dietz at Johns Hopkins with this. He's the guy that did the study on the mice, and will be conducting clinical trials in the fall. He asked me to help him gather names of people with mfs that have been using ARBs, since I knew a couple. Most of the people that I received responses from had a positive effect. One person had a VERY positive effect. One had no effect at all, but she seemed to be an extreme marfan case. Largely depends on the person, dosage and specific ARB, I guess!

[Cleveland Clinic]

nick,

The data you are referring to is from a recent study and is observational data in an animal model. It is hard to extrapolate to clinical practice, and often what wee see in animal models doesnt play out.

That said, generall my practice for patients with aortic aneurysms involves strict blood pressure control, first with beta blockers.  
the usually next with usually an ACE inhibitor or an ARB if there is a rason not to use an ACE.  As far as dosing, I usually titrate to blood pressure.

good luck