A randomized, double blind pilot study to assess the effects of losartan vs. atenolol on the biophysical properties of the aorta in patients with Marfan and Loeys-Dietz syndromes

George G S Sandor; Mohammed H Alghamdi; Leslie A Raffin; Mary T Potts; Lindsey D Williams; James E Potts; Marla Kiess; Casey van Breemen

doi:10.1016/j.ijcard.2014.11.082

A randomized, double blind pilot study to assess the effects of losartan vs. atenolol on the biophysical properties of the aorta in patients with Marfan and Loeys-Dietz syndromes

Int J Cardiol. 2015 Jan 20:179:470-5. doi: 10.1016/j.ijcard.2014.11.082. Epub 2014 Nov 8.

Authors

George G S Sandor¹, Mohammed H Alghamdi², Leslie A Raffin², Mary T Potts², Lindsey D Williams², James E Potts², Marla Kiess³, Casey van Breemen⁴

Affiliations

¹ Children's Heart Centre, British Columbia Children's Hospital, The University of British Columbia, Vancouver, Canada. Electronic address: [email protected].
² Children's Heart Centre, British Columbia Children's Hospital, The University of British Columbia, Vancouver, Canada.
³ Division of Cardiology, Department of Medicine, St. Paul's Hospital, The University of British Columbia, Vancouver, Canada.
⁴ Department of Pharmacology and Therapeutics, The University of British Columbia, Vancouver, Canada.

PMID: 25465809
DOI: 10.1016/j.ijcard.2014.11.082

Abstract

Background: Patients with Marfan (MFS) and Loeys-Dietz (LDS) syndromes have been shown to have abnormal aortic biophysical properties. The purpose of this study was to compare the effects of 12-months of therapy with atenolol or losartan on vascular function in young patients with MFS and LDS.

Methods: Seventeen patients with MFS or LDS were recruited and randomized to treatment with atenolol, 25-50mg, or losartan, 25mg daily. Prior to treatment and following therapy, echocardiography for left ventricular size, function and aortic root size was performed. Pulse wave velocity (PWV), input (Zi, ZiF) and characteristic (Zc, ZcF) impedances, arterial stiffness (Ep and β-index), total arterial compliance (TAC), mean (Wm) and total (Wt) hydraulic power, efficiency, power cost per unit of forward flow (Wt/CI) and brachial artery flow-mediated dilation (FMD) were measured.

Results: The atenolol group consisted of 9 females (17.6years) and the losartan group 7 males and 1 female (17.0years). Their height, weight, BSA, BMI, systolic and diastolic blood pressures were similar. Baseline to 12-month changes for atenolol and losartan were PWV (20% vs -14%), Zi (-2% vs -27%), Zc (-20% vs -27%), Ep (1%, vs -13%), β-index (10% vs 14%), FMD (11% vs 20%), TAC (3% vs 42%), Wm (-24% vs 15%), Wt (-24% vs 17%), and Wt/CI (3% vs 21%). There was a trend for losartan to decrease PWV and stiffness indexes while atenolol decreased power and power/unit flow.

Conclusion: This pilot study suggests that atenolol and losartan may have different mechanisms of action on vascular function. A larger clinical trial is needed to confirm these effects.Clinical trials registration NCT00593710 (ClinicalTrials.gov).

Keywords: Atenolol; Clinical trial; Loeys–Dietz syndrome; Losartan; Marfan syndrome; Vascular function.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adrenergic beta-1 Receptor Antagonists / therapeutic use*
Angiotensin II Type 1 Receptor Blockers / therapeutic use*
Aorta / drug effects*
Aorta / physiopathology*
Atenolol / therapeutic use*
Double-Blind Method
Echocardiography
Endothelium, Vascular / drug effects
Endothelium, Vascular / physiopathology
Female
Humans
Loeys-Dietz Syndrome / drug therapy*
Loeys-Dietz Syndrome / physiopathology*
Losartan / therapeutic use*
Male
Marfan Syndrome / drug therapy*
Marfan Syndrome / physiopathology*
Pilot Projects
Pulse Wave Analysis
Treatment Outcome

Substances

Adrenergic beta-1 Receptor Antagonists
Angiotensin II Type 1 Receptor Blockers
Atenolol
Losartan

Associated data

ClinicalTrials.gov/NCT00593710