title: Effects of Sacubitril/Valsartan Versus Olmesartan on Central Hemodynamics in the Elderly With Systolic Hypertension: The PARAMETER Study.
abstract: Effective treatment of systolic hypertension in elderly patients remains a major therapeutic challenge. A multicenter, double-blind, randomized controlled trial with sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, was conducted to determine its effects versus olmesartan (angiotensin receptor blocker) on central aortic pressures, in elderly patients (aged ≥60 years) with systolic hypertension and pulse pressure >60 mm Hg, indicative of arterial stiffness. Patients (n=454; mean age, 67.7 years; mean seated systolic blood pressure, 158.6 mm Hg; mean seated pulse pressure, 69.7 mm Hg) were randomized to receive once-daily sacubitril/valsartan 200 mg or olmesartan 20 mg, force titrated to double the initial doses after 4 weeks, before primary assessment at 12 weeks. The study extended double-blind treatment for 12 to 52 weeks, during which amlodipine (2.5-5 mg) and subsequently hydrochlorothiazide (6.25-25 mg) were added-on for patients not achieving blood pressure target (<140/90). At week 12, sacubitril/valsartan reduced central aortic systolic pressure (primary assessment) greater than olmesartan by -3.7 mm Hg (P=0.010), further corroborated by secondary assessments at week 12 (central aortic pulse pressure, -2.4 mm Hg,P<0.012; mean 24-hour ambulatory brachial systolic blood pressure and central aortic systolic pressure, -4.1 mm Hg and -3.6 mm Hg, respectively, bothP<0.001). Differences in 24-hour ambulatory pressures were pronounced during sleep. After 52 weeks, blood pressure parameters were similar between treatments (P<0.002); however, more patients required add-on antihypertensive therapy with olmesartan (47%) versus sacubitril/valsartan (32%;P<0.002). Both treatments were equally well tolerated. The PARAMETER study (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Measuring Arterial Stiffness in the Elderly), for the first time, demonstrated superiority of sacubitril/valsartan versus olmesartan in reducing clinic and ambulatory central aortic and brachial pressures in elderly patients with systolic hypertension and stiff arteries.
authors.affiliation: From the Department of Cardiovascular Sciences, University College London (UCL), United Kingdom (B.W.); National Institute for Health Research, University College London Hospitals Biomedical Research Centre, United Kingdom (B.W.); Department of Cardiology, University of Cardiff, Wales, United Kingdom (J.R.C.); Jichi Medical School, Tochigi, Japan (K.K.); Novartis Pharmaceuticals Corporation, East Hanover, NJ (D.H.Z., W.G.); Novartis Pharma AG, Basel, Switzerland (P.C.B.); Beijing Novartis Pharma Co, Ltd, Shanghai, China (Q.W.). bryan.williams@ucl.ac.uk.
authors.forename: Bryan
authors.initials: B
authors.lastname: Williams
authors.affiliation: From the Department of Cardiovascular Sciences, University College London (UCL), United Kingdom (B.W.); National Institute for Health Research, University College London Hospitals Biomedical Research Centre, United Kingdom (B.W.); Department of Cardiology, University of Cardiff, Wales, United Kingdom (J.R.C.); Jichi Medical School, Tochigi, Japan (K.K.); Novartis Pharmaceuticals Corporation, East Hanover, NJ (D.H.Z., W.G.); Novartis Pharma AG, Basel, Switzerland (P.C.B.); Beijing Novartis Pharma Co, Ltd, Shanghai, China (Q.W.).
authors.forename: John R
authors.initials: JR
authors.lastname: Cockcroft
authors.affiliation: From the Department of Cardiovascular Sciences, University College London (UCL), United Kingdom (B.W.); National Institute for Health Research, University College London Hospitals Biomedical Research Centre, United Kingdom (B.W.); Department of Cardiology, University of Cardiff, Wales, United Kingdom (J.R.C.); Jichi Medical School, Tochigi, Japan (K.K.); Novartis Pharmaceuticals Corporation, East Hanover, NJ (D.H.Z., W.G.); Novartis Pharma AG, Basel, Switzerland (P.C.B.); Beijing Novartis Pharma Co, Ltd, Shanghai, China (Q.W.).
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Kario
authors.affiliation: From the Department of Cardiovascular Sciences, University College London (UCL), United Kingdom (B.W.); National Institute for Health Research, University College London Hospitals Biomedical Research Centre, United Kingdom (B.W.); Department of Cardiology, University of Cardiff, Wales, United Kingdom (J.R.C.); Jichi Medical School, Tochigi, Japan (K.K.); Novartis Pharmaceuticals Corporation, East Hanover, NJ (D.H.Z., W.G.); Novartis Pharma AG, Basel, Switzerland (P.C.B.); Beijing Novartis Pharma Co, Ltd, Shanghai, China (Q.W.).
authors.forename: Dion H
authors.initials: DH
authors.lastname: Zappe
authors.affiliation: From the Department of Cardiovascular Sciences, University College London (UCL), United Kingdom (B.W.); National Institute for Health Research, University College London Hospitals Biomedical Research Centre, United Kingdom (B.W.); Department of Cardiology, University of Cardiff, Wales, United Kingdom (J.R.C.); Jichi Medical School, Tochigi, Japan (K.K.); Novartis Pharmaceuticals Corporation, East Hanover, NJ (D.H.Z., W.G.); Novartis Pharma AG, Basel, Switzerland (P.C.B.); Beijing Novartis Pharma Co, Ltd, Shanghai, China (Q.W.).
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Brunel
authors.affiliation: From the Department of Cardiovascular Sciences, University College London (UCL), United Kingdom (B.W.); National Institute for Health Research, University College London Hospitals Biomedical Research Centre, United Kingdom (B.W.); Department of Cardiology, University of Cardiff, Wales, United Kingdom (J.R.C.); Jichi Medical School, Tochigi, Japan (K.K.); Novartis Pharmaceuticals Corporation, East Hanover, NJ (D.H.Z., W.G.); Novartis Pharma AG, Basel, Switzerland (P.C.B.); Beijing Novartis Pharma Co, Ltd, Shanghai, China (Q.W.).
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: From the Department of Cardiovascular Sciences, University College London (UCL), United Kingdom (B.W.); National Institute for Health Research, University College London Hospitals Biomedical Research Centre, United Kingdom (B.W.); Department of Cardiology, University of Cardiff, Wales, United Kingdom (J.R.C.); Jichi Medical School, Tochigi, Japan (K.K.); Novartis Pharmaceuticals Corporation, East Hanover, NJ (D.H.Z., W.G.); Novartis Pharma AG, Basel, Switzerland (P.C.B.); Beijing Novartis Pharma Co, Ltd, Shanghai, China (Q.W.).
authors.forename: Weinong
authors.initials: W
authors.lastname: Guo
mesh_terms: D000368:Aged; D000613:Aminobutyrates / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage; D001713:Biphenyl Compounds; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013599:Systole; D013777:Tetrazoles / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; D007093:Imidazoles; D013777:Tetrazoles; D000068756:Valsartan; C437965:olmesartan; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: central pressure; elderly; sacubitril/valsartan; systolic hypertension