Rationale and design of a randomized clinical trial of β-blocker therapy (atenolol) versus angiotensin II receptor blocker therapy (losartan) in individuals with Marfan syndrome

Abstract

Background-Cardiovascular pathology, including aortic root dilation, dissection, and rupture, is the leading cause of mortality in patients with Marfan syndrome (MFS). The maximal aortic root diameter at the sinuses of Valsalva is considered the best predictor of adverse cardiovascular outcome. Although advances in therapy have improved life expectancy, affected individuals continue to suffer cardiovascular morbidity and mortality. Recent studies in a FBN1-targeted mouse model of MFS with aortic pathology similar to that seen in humans showed that treatment with losartan normalized aortic root growth and aortic wall architecture.

2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease: Executive Summary

“…An angiotensin receptor blocker (losartan) is reason able for patients with Marfan syndrome, to reduce the rate of aortic dilatation unless contraindicated. 105,112 (Level of Evidence: B)…”

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

“…Importantly for clinical management of MFS patients, the Food and Drug Administration (FDA)-approved angiotensin II type 1 receptor (AT1) blocker losartan, an antihypertensive drug, has been shown to reduce TGF-b signaling and ameliorate many manifestations of MFS in mouse models (Neptune et al 2003;Ng et al 2004;Habashi et al 2006;Cohn et al 2007;Lacro et al 2007). Additionally, in a randomized clinical trial of pediatric MFS patients, losartan, at the FDA-recommended dose for hypertension, was shown to be equally effective as atenolol used at a dose far above the FDA-recommended daily dose, with both drugs leading to a significant decline in Z-score over time (body size-indexed aortic root dimension over time) (Lacro et al 2014;Mallat and Daugherty 2015).…”

Choroby zastawki mitralnej w zespole Marfana

“…Stosowanie losartanu ograniczało również objawy fenotypowe w tkankach nienależących do układu sercowo-naczyniowego, między innymi w pęcherzykach płucnych i mięśniach szkieletowych [26]. Toczą się badania na zwierzętach z MFS oraz z udziałem chorych na MFS, których celem jest ocena wpływu selektywnych antagonistów receptora AT 1 oraz antagonistów receptora adrenergicznego na przeżycie, zmniejszenie wymiarów aorty oraz patologie MV [27].…”