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 dilatation over three years among the
losartan users compared with study patients given
atenolol, with both groups of patients experiencing a similar decrease in the rate of dilatation over the 3 year follow-up. Both studies suggest a positive impact of
losartan on aortic dilation in humans with Marfan, but they also highlight a number of important questions that remain unanswered. Further trials are clearly needed in order to assess optimal dosing and to guide timing of
therapy, and also to further assess the potential and comparative effectiveness of both
losartan and β-blockers, individually and in combination, as therapeutic treatments for aortic protection of different groups of patients with
Marfan syndrome.