COMPARE and Pediatric Heart Network Investigator trials: Losartan finally validated in humans with Marfan, but much work remains!

Global Cardiology Science & Practice
Magdi Yacoub, Mark Radford

Abstract

A landmark study by Habashi et al(1) in 2006 documented for the first time both the prevention and reversal of structural changes in the aorta associated with Marfan syndrome, via pharmacological means. This study, carried out in a rat model, concluded that such results were due to an inhibitor effect by the drug losartan on TGB-β1 (Figure 1). Habashi's paper prompted some physicians, in the absence of human trials, to begin the clinical off-label use of losartan on Marfan patients, arguing that this was justified due to the drug's excellent safety profile. This has caused some controversy. Two significant randomized human trials of losartan in Marfan patients have since been conducted, which contribute different but valuable elements to the debate; the COMPARE trial demonstrated a significantly lower increase in aortic root diameter among study subjects receiving losartan compared with a placebo group after 3 years, although no significant differences were observed in aortic diameter beyond the root itself. A more recently concluded trial by Lacro et al(2) from the Paediatric Heart Network, comparing losartan with atenolol (and no placebo group), appeared to show no comparative benefit with respect to the rate of aortic dilata...Continue Reading

References

Apr 24, 1996·American Journal of Medical Genetics·A De PaepeR E Pyeritz
Aug 25, 2006·The New England Journal of Medicine·Bart L LoeysHarry C Dietz
Jun 27, 2008·The New England Journal of Medicine·Benjamin S BrookeHarry C Dietz
Sep 4, 2013·European Heart Journal·Maarten GroeninkBarbara J M Mulder
Nov 19, 2014·The New England Journal of Medicine·Juan M Bowen, Heidi M Connolly
Nov 19, 2014·The New England Journal of Medicine·Ronald V LacroUNKNOWN Pediatric Heart Network Investigators

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Citations

Nov 12, 2020·Clinical Genetics·Amparo HernándizPilar Sepúlveda

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Methods Mentioned

BETA
dissection

Software Mentioned

COMPARE
Lacro

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