The effect of sacubitril/valsartan compared to olmesartan on cardiovascular remodelling in subjects with essential hypertension: the results of a randomized, double-blind, active-controlled study

Schmieder, R. E. et al. (2017) The effect of sacubitril/valsartan compared to olmesartan on cardiovascular remodelling in subjects with essential hypertension: the results of a randomized, double-blind, active-controlled study. European Heart Journal, 38(44), pp. 3308-3317. (doi: 10.1093/eurheartj/ehx525) (PMID:29029087)

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Abstract

Aims: Progressive aortic stiffening eventually leads to left ventricular (LV) hypertrophy and heart failure if left untreated. Anti-hypertensive agents have been shown to reverse this to some extent. The effects of sacubitril/valsartan (LCZ696), a dual-action angiotensin receptor blocker (ARB), and neprilysin inhibitor, on arterial stiffness and LV remodelling have not been investigated. Methods and results: This was a randomized, multi-centre, double-blind, double-dummy, active-controlled, parallel group, study to compare the effects on cardiovascular remodelling of sacubitril/valsartan with those of olmesartan in patients with hypertension and elevated pulse pressure. Magnetic resonance imaging scans were used to assess LV mass and local aortic distensibility, at baseline and at 12 and 52 weeks after initiation of treatment. Central pulse and systolic pressure were determined using a SphymoCor® XCEL device at each time point. A total of 114 patients were included, with 57 in each treatment group. The mean age was 59.8 years, and 67.5% were male. Demographic characteristics did not vary between the two sets of patients. Left ventricular mass index decreased to a greater extent in the sacubitril/valsartan group compared to the olmesartan group from baseline to 12 weeks (−6.36 vs. −2.32 g/m2; P = 0.039) and from baseline to 52 weeks (−6.83 vs. −3.55 g/m2; P = 0.029). These differences remained significant after adjustment for systolic blood pressure (SBP) at follow-up (P = 0.036 and 0.019 at 12 and 52 weeks, respectively) and similar signals (though formally non-significant) were observed after adjusting for changes in SBP (P = 0.0612 and P = 0.0529, respectively). There were no significant differences in local distensibility changes from baseline to 12 or 52 weeks between the two groups; however, there was a larger reduction in central pulse pressure for the sacubitril/valsartan group compared to the olmesartan group (P = 0.010). Conclusion: Since LV mass change correlates with cardiovascular prognosis, the greater reductions in LV mass indicate valuable advantages of sacubitril/valsartan compared to olmesartan. The finding that LV mass index decrease might be to some extent independent of SBP suggests that the effect of the dual-acting agent may go beyond those due to its BP-lowering ability.

Item Type:Articles
Keywords:Angiotensin, arterial stiffness, heart failure, hypertension, left ventricular hypertrophy, neprilysin.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Delles, Professor Christian
Authors: Schmieder, R. E., Wagner, F., Mayr, M., Delles, C., Ott, C., Keicher, C., Hrabak-Paar, M., Heye, T., Aichner, S., Khder, Y., Yates, D., Albrecht, D., Langenickel, T., Freyhardt, P., Janka, R., and Bremerich, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN:0195-668X
ISSN (Online):1522-9645
Published Online:27 September 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in European Heart Journal 38(44):3308-3317
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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