Use cases Losartan and Marfan

Did losartan for Marfan syndrome hold up in the clinic?

A trial can look like a failure for reasons that have nothing to do with the drug. We read every registered trial of losartan in Marfan syndrome: how each one ended, and what losartan was up against.

WorkflowPrior Art & Failed Trial Check
8registered trials
0stopped for lack of efficacy
1terminated, not for futility
608patients in the largest trial

Marfan syndrome is caused by mutations in the gene for fibrillin-1.1 Its gravest risk is the aorta. The aortic root slowly enlarges, aortic-root dissection is the leading cause of death, and beta-blockers were the standard treatment in most centres.2

In 2006, a study in a mouse model of the disease found that losartan, a blood pressure drug already in clinical use, prevented aortic aneurysm, and its authors proposed testing it in patients.1 Trials soon followed: the first registered one started in January 2007.3

We used the Prior Art & Failed Trial Check workflow to find every registered trial of losartan in Marfan syndrome and read how each one ended.

It searched ClinicalTrials.gov3 under 18 names for losartan, from Cozaar to its development codes, alone and with 6 names for the disease. It kept the 8 interventional trials that test losartan in the disease, recorded each one's status, comparator and stated reason for stopping, and looked up their papers, and the meta-analyses that pooled them, in PubMed.

Eight trials, none stopped for lack of efficacy

ClinicalTrials.gov lists 8 trials that test losartan in Marfan syndrome, all started between 2007 and 2009. Four are completed, three have an unknown status and one was terminated.3

That one, the 303-patient Marfan Sartan trial against placebo, didn't stop for futility. Its stated reason: a similar publication suggested sartans help, and only 15 patients were left for their 36-month visit. Its own paper found no significant difference in aortic-root growth over a median 3.5 years.4

Registered losartan trials in Marfan syndrome
Registered losartan trials in Marfan syndrome
100%

The catch

The largest trial, 608 children and young adults, found losartan no better than atenolol at slowing aortic-root growth (P=0.08).2 A 140-patient Spanish trial agreed.5 Read quickly, that's a failed drug.

But atenolol isn't a placebo. With either drug the aortic-root Z-score fell,2 and a 2022 meta-analysis of individual patients' data found the two drug classes alike (P=0.48).6 Losartan didn't fail. It just didn't beat the standard drug.

Slower aortic-root growth against no added drug

In the same meta-analysis, four trials set an angiotensin receptor blocker, losartan in all but one, against placebo or no added drug. It roughly halved the yearly rise in aortic-root Z-score: 0.07 against 0.13 (P=0.012).6

The Dutch COMPARE trial, losartan or nothing extra in 233 adults, found the same: 0.77 against 1.35 mm of root growth over three years of follow-up (P=0.014).7

Neither COMPARE nor a 2019 meta-analysis of seven trials found fewer dissections, operations or deaths.7, 8

Page 1 of the report: summary and findingsPage 2 of the report: flags, methods and limitationsPage 3 of the report: references
Download the report (PDF)

Limitations

  • Long-term COMPARE follow-up reports fewer deaths and dissections, but it is observational, since patients chose whether to stay on losartan.9
  • Several trials are small or open-label, and none has dissection, surgery or death as its main outcome.
  • The registry search covered ClinicalTrials.gov. COMPARE, registered in the Netherlands, came in through its papers.7, 10

Sources

  1. 1Habashi JP, Judge DP, Holm TM, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006;312(5770):117-121.
  2. 2Lacro RV, Dietz HC, Sleeper LA, et al. Atenolol versus losartan in children and young adults with Marfan's syndrome. N Engl J Med. 2014;371(22):2061-2071.
  3. 3ClinicalTrials.gov, US National Library of Medicine. Records NCT00429364, NCT00763893, NCT00683124, NCT01145612, NCT00723801, NCT00782327, NCT00651235 and NCT00593710, through the ClinicalTrials.gov API v2, accessed 27 October 2026.
  4. 4Milleron O, Arnoult F, Ropers J, et al. Marfan Sartan: a randomized, double-blind, placebo-controlled trial. Eur Heart J. 2015;36(32):2160-2166.
  5. 5Forteza A, Evangelista A, Sánchez V, et al. Efficacy of losartan vs. atenolol for the prevention of aortic dilation in Marfan syndrome: a randomized clinical trial. Eur Heart J. 2016;37(12):978-985.
  6. 6Pitcher A, Spata E, Emberson J, et al. Angiotensin receptor blockers and β blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials. Lancet. 2022;400(10355):822-831.
  7. 7Groenink M, den Hartog AW, Franken R, et al. Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial. Eur Heart J. 2013;34(45):3491-3500.
  8. 8Elbadawi A, Omer MA, Elgendy IY, et al. Losartan for preventing aortic root dilatation in patients with Marfan syndrome: a meta-analysis of randomized trials. Cardiol Ther. 2019;8(2):365-372.
  9. 9van Andel MM, Indrakusuma R, Jalalzadeh H, et al. Long-term clinical outcomes of losartan in patients with Marfan syndrome: follow-up of the multicentre randomized controlled COMPARE trial. Eur Heart J. 2020;41(43):4181-4187.
  10. 10Radonic T, de Witte P, Baars MJ, et al. Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE trial. Trials. 2010;11:3. Netherlands Trial Register NTR1423.

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