Recent Clinical Drug Trials Evidence in Marfan Syndrome and Clinical Implications

Marfan syndrome is a genetic disorder of connective tissue with principal manifestations in the cardiovascular, ocular, and skeletal systems. Cardiovascular disease, mainly progressive aortic root dilation and aortic dissection, is the leading cause of morbidity and mortality. The primary aims of this report were to examine the evidence related to medical therapy for Marfan syndrome, including recently completed randomized clinical trials on the efficacy of β-blockers and angiotensin II receptor blockers for the prophylactic treatment of aortic enlargement in Marfan syndrome, and to provide recommendations for medical therapy on the basis of available evidence. Medical therapy for Marfan syndrome should be individualized according to patient tolerance and risk factors such as age, aortic size, and family history of aortic dissection. The Pediatric Heart Network trial showed that atenolol and losartan each reduced the rate of aortic dilation. All patients with known or suspected Marfan syndrome and aortic root dilation should receive medical therapy with adequate doses of either β-blocker or angiotensin receptor blocker. The Pediatric Heart Network trial also showed that atenolol and losartan are more effective at reduction of aortic root z score in younger subjects, which suggests that medical therapy should be prescribed even in the youngest children with aortic dilation. For patients with Marfan syndrome without aortic dilation, the available evidence is less clear. If aortic dilation is severe and/or progressive, therapy with a combination of β-blocker and angiotensin receptor blocker should be considered, although trial results are mixed with respect to the efficacy of combination therapy vs monotherapy.