By now you’ve likely read the synopsis of the atenolol vs losartan trial results. Perhaps you’ve read them from multiple sources and are a little confused. Maybe the results are what you expected and you’re happy, or maybe you’re feeling disappointed. Was the trial a success or a failure? Where do we go from here?
Here are my thoughts!
Does losartan work? Yes! The trial showed that both losartan and atenolol work. It seems like people are disappointed because the trial showed that they work the same, and their expectation was that losartan would work better. However, there was a dosing issue. Losartan was compared to a very high dose of atenolol (up to 2x the FDA recommended dose commonly used for people with Marfan syndrome). The losartan was dosed at up to the FDA maximum dose for treating people with hypertension (so not everyone in the study received the maximum dose). In the past, most people with Marfan were prescribed much less atenolol than was used in the trial. And, the amount of losartan prescribed to patients in clinics over the last few years has varied greatly.
Why is this important? If the atenolol had been dosed at a more clinical level, and losartan where it is, or at a higher level (more in line with what some doctors are using clinically), the results might have been different. All we can say from this trial is that losartan and atenolol work equally well at the particular doses from the trial. The results can’t be generalized to other doses. Another important takeaway is that for those on beta blockers, this higher dose is potentially necessary for the best effects.
Why was the atenolol dose so high? My understanding is that because we’d never had a double blind trial (where patients and the trial site administrators don’t know which drug the patients are taking) to prove the effectiveness of beta blockers before (though there were other studies!), these researchers also wanted to prove beyond a shadow of a doubt whether beta blockers were effective at managing aortic growth in Marfan patients. They definitely accomplished this, though the remaining question is whether this might have muddied the comparative effects of losartan at all.
Kids vs adults: The researchers discovered that optimum results occurred in young kids. This provides evidence for what a lot of us have been thinking: it’s important to start our kids on medication early. This makes me feel even more confident in our decision to start J on medication when he was 2.5 years old.
Placebo: The New York Times article (which, I want to point out, neglected to explain the dosing issue with this study) talked about the fact there wasn’t a placebo in this trial and seemed to question the efficacy of the results because of this. In light of the article, I’ve seen a few people asking why there wasn’t a placebo. There was no placebo because it wouldn’t have been ethical. Prior to this study, there was a standard of care for treatment: beta blockers. It’s generally frowned upon to do a high-risk study (in terms of risk to the participants; in this case, the risk of dissection) with a placebo when a standard of care exists already. And let’s be honest: this is a trial looking mostly at children. Would you have taken your child off treatment to enter a study where there was a 50% chance they’d have had NO treatment for their existing aortic aneurysm for 3 years, thereby increasing the risk of needing surgery or having a dissection during that time? No way! This study was designed to be as safe as possible for the patients enrolled and therefore it was set up to compare two drugs against each other. While some researchers might have argued a placebo would have been “better science,” it wouldn’t have been in the best interest for our community.
This study doesn’t have all the answers. It was never going to have all the answers…no single study can! But because of this, other studies are going on all over the world. Some have already been published. These studies ask other questions. They look at whether other ARBs, like irbersartan, might be better than losartan. They see whether losartan + atenolol is better than either drug alone. They study different age groups. There are also ancillary studies to the US trial, which are looking at whether or not losartan affects other body systems.
I am glad to know that losartan is a valid “tool in the Marfan toolbox.” This is an option for people who can’t tolerate beta blockers for whatever reason, and now we know a little more about dosing beta blockers. Over the next few years, we’ll learn even more about what ARBs can and can not do for us, and I am confident that other drug options will be brought forward to be tested as well. Every step forward in finding preventive treatments for aortic aneurysms is a success!
If you haven’t already, consider signing up for the interactive webinar with the study’s principal investigator, Dr. Ron Lacro of Boston Children’s Hospital. He’ll explain more about the study and take your questions. It’s a great opportunity! In addition, the Marfan Foundation will be planning another webinar with Dr. Hal Dietz shortly. The Foundation has also put together a Q&A, which you can find here.
The opinions offered at Musings of a Marfan Mom are for informational purposes only and are not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a qualified healthcare provider with any questions you may have regarding Marfan syndrome and any medical condition. Never disregard professional medical advice or delay in seeking care because of something you have read here.