Roland E Schmieder1, Frank Wagner2, Michael Mayr3, Christian Delles4, Christian Ott1, Christian Keicher2, Maja Hrabak-Paar3,5, Tobias Heye3, Solveig Aichner3, Yasser Khder6, Denise Yates7, Diego Albrecht6, Thomas Langenickel6, Patrick Freyhardt2, Rolf Janka8, Jens Bremerich3. 1. Department of Nephrology and Hypertension, University Hospital Erlangen, Ulmenweg 18, 91054 Erlangen, Germany. 2. Charité Research Organisation, Berlin, Charité Research Organisation GmbH, Charitéplatz 1, 10117 Berlin (Mitte), Germany. 3. Outpatient Department, University Hospital Basel, Basel, Switzerland. 4. Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK. 5. University Hospital Center Zagreb, University of Zagreb School of Medicine, Kišpatićeva 12 (Rebro), 10 000 Zagreb, Croatia. 6. Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland. 7. Novartis Institutes for BioMedical Research, Inc., 250 Massachusetts Avenue, Cambridge, MA 02139, USA. 8. Department of Radiology, University Hospital Erlangen, Maximiliansplatz 1, 91054 Erlangen, Germany.
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. Published on behalf of the European Society of Cardiology. All rights reserved.
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. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Bharathi Upadhya; Michael V Rocco; Nicholas M Pajewski; Tim Morgan; Joseph Blackshear; William Greg Hundley; Suzanne Oparil; Elsayed Z Soliman; Debbie L Cohen; Craig A Hamilton; Monique E Cho; William J Kostis; Vasilios Papademetriou; Carlos J Rodriguez; Dominic S Raj; Ray Townsend; Sujethra Vasu; Sara Zamanian; Dalane W Kitzman Journal: Hypertension Date: 2019-07-01 Impact factor: 10.190
Authors: Maja Hrabak-Paar; Achim Kircher; Saeed Al Sayari; Sebastien Kopp; Francesco Santini; Roland E Schmieder; Nadjia Kachenoura; Denise Yates; Thomas Langenickel; Jens Bremerich; Tobias Heye Journal: Radiol Cardiothorac Imaging Date: 2020-04-30