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Tytuł:
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Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease.
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Autorzy:
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Haynes R; Medical Research Council Population Health Research Unit (R.H., P.K.J., W.G.H., B.C.S., M.H., M.J.L., C.B.), University of Oxford, UK.; Clinical Trial Service Unit (R.H., P.K.J., N.S., W.G.H., B.C.S., L.B., M.H., M.J.L., C.B.), University of Oxford, UK.
Judge PK; Medical Research Council Population Health Research Unit (R.H., P.K.J., W.G.H., B.C.S., M.H., M.J.L., C.B.), University of Oxford, UK.; Clinical Trial Service Unit (R.H., P.K.J., N.S., W.G.H., B.C.S., L.B., M.H., M.J.L., C.B.), University of Oxford, UK.
Staplin N; Clinical Trial Service Unit (R.H., P.K.J., N.S., W.G.H., B.C.S., L.B., M.H., M.J.L., C.B.), University of Oxford, UK.
Herrington WG; Medical Research Council Population Health Research Unit (R.H., P.K.J., W.G.H., B.C.S., M.H., M.J.L., C.B.), University of Oxford, UK.; Clinical Trial Service Unit (R.H., P.K.J., N.S., W.G.H., B.C.S., L.B., M.H., M.J.L., C.B.), University of Oxford, UK.
Storey BC; Medical Research Council Population Health Research Unit (R.H., P.K.J., W.G.H., B.C.S., M.H., M.J.L., C.B.), University of Oxford, UK.; Clinical Trial Service Unit (R.H., P.K.J., N.S., W.G.H., B.C.S., L.B., M.H., M.J.L., C.B.), University of Oxford, UK.
Bethel A; Nuffield Department of Population Health, and Diabetes Trials Unit, Radcliffe Department of Medicine (A.B.), University of Oxford, UK.
Bowman L; Clinical Trial Service Unit (R.H., P.K.J., N.S., W.G.H., B.C.S., L.B., M.H., M.J.L., C.B.), University of Oxford, UK.
Brunskill N; Department of Infection, Immunity and Inflammation, University of Leicester, UK (N.B.).
Cockwell P; Department of Nephrology, University Hospitals Birmingham, UK (P.C.).
Hill M; Medical Research Council Population Health Research Unit (R.H., P.K.J., W.G.H., B.C.S., M.H., M.J.L., C.B.), University of Oxford, UK.; Clinical Trial Service Unit (R.H., P.K.J., N.S., W.G.H., B.C.S., L.B., M.H., M.J.L., C.B.), University of Oxford, UK.
Kalra PA; Department of Nephrology, Salford Royal Hospital NHS Foundation Trust, UK (P.A.K.).
McMurray JJV; Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (J.J.V.M.).
Taal M; Faculty of Medicine and Health Sciences, University of Nottingham, UK (M.T.).
Wheeler DC; Centre for Nephrology, University College London, UK (D.C.W.).
Landray MJ; Medical Research Council Population Health Research Unit (R.H., P.K.J., W.G.H., B.C.S., M.H., M.J.L., C.B.), University of Oxford, UK.; Clinical Trial Service Unit (R.H., P.K.J., N.S., W.G.H., B.C.S., L.B., M.H., M.J.L., C.B.), University of Oxford, UK.
Baigent C; Medical Research Council Population Health Research Unit (R.H., P.K.J., W.G.H., B.C.S., M.H., M.J.L., C.B.), University of Oxford, UK.; Clinical Trial Service Unit (R.H., P.K.J., N.S., W.G.H., B.C.S., L.B., M.H., M.J.L., C.B.), University of Oxford, UK.
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Źródło:
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Circulation [Circulation] 2018 Oct 09; Vol. 138 (15), pp. 1505-1514.
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Typ publikacji:
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Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: [Dallas, Tex., etc., American Heart Association, etc.]
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MeSH Terms:
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Aminobutyrates/*therapeutic use
Angiotensin II Type 1 Receptor Blockers/*therapeutic use
Glomerular Filtration Rate/*drug effects
Heart Failure/*drug therapy
Irbesartan/*therapeutic use
Kidney/*drug effects
Renal Insufficiency, Chronic/*physiopathology
Stroke Volume/*drug effects
Tetrazoles/*therapeutic use
Ventricular Function, Left/*drug effects
Aged ; Aminobutyrates/adverse effects ; Angiotensin II Type 1 Receptor Blockers/adverse effects ; Biphenyl Compounds ; Blood Pressure/drug effects ; Double-Blind Method ; Drug Combinations ; Female ; Heart Failure/diagnosis ; Heart Failure/mortality ; Heart Failure/physiopathology ; Humans ; Irbesartan/adverse effects ; Kidney/physiopathology ; Male ; Middle Aged ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/mortality ; Tetrazoles/adverse effects ; Time Factors ; Treatment Outcome ; United Kingdom ; Valsartan
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Grant Information:
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MC_U137686849 United Kingdom MRC_ Medical Research Council; MC_U137686855 United Kingdom MRC_ Medical Research Council; MC_U137686861 United Kingdom MRC_ Medical Research Council; MC_UU_12026/6 United Kingdom MRC_ Medical Research Council
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Contributed Indexing:
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Keywords: chronic kidney disease; neprilysin inhibition; renin-angiotensin system
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Molecular Sequence:
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ISRCTN ISRCTN11958993
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Substance Nomenclature:
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0 (Aminobutyrates)
0 (Angiotensin II Type 1 Receptor Blockers)
0 (Biphenyl Compounds)
0 (Drug Combinations)
0 (Tetrazoles)
80M03YXJ7I (Valsartan)
J0E2756Z7N (Irbesartan)
WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination)
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Entry Date(s):
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Date Created: 20180714 Date Completed: 20190930 Latest Revision: 20211204
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Update Code:
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20240105
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DOI:
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10.1161/CIRCULATIONAHA.118.034818
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PMID:
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30002098
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Background: Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, but its effects on kidney function and cardiac biomarkers in people with moderate to severe chronic kidney disease are unknown.
Methods: The UK HARP-III trial (United Kingdom Heart and Renal Protection-III), a randomized double-blind trial, included 414 participants with an estimated glomerular filtration rate (GFR) 20 to 60 mL/min/1.73 m 2 who were randomly assigned to sacubitril/valsartan 97/103 mg twice daily versus irbesartan 300 mg once daily. The primary outcome was measured GFR at 12 months using ANCOVA with adjustment for each individual's baseline measured GFR. All analyses were by intention to treat.
Results: In total, 207 participants were assigned to sacubitril/valsartan and 207 to irbesartan. Baseline measured GFR was 34.0 (SE, 0.8) and 34.7 (SE, 0.8) mL/min/1.73 m 2 , respectively. At 12 months, there was no difference in measured GFR: 29.8 (SE 0.5) among those assigned sacubitril/valsartan versus 29.9 (SE, 0.5) mL/min/1.73 m 2 among those assigned irbesartan; difference, -0.1 (0.7) mL/min/1.73 m 2 . Effects were similar in all prespecified subgroups. There was also no significant difference in estimated GFR at 3, 6, 9, or 12 months and no clear difference in urinary albumin:creatinine ratio between treatment arms (study average difference, -9%; 95% CI, -18 to 1). However, compared with irbesartan, allocation to sacubitril/valsartan reduced study average systolic and diastolic blood pressure by 5.4 (95% CI, 3.4-7.4) and 2.1 (95% CI, 1.0-3.3) mm Hg and levels of troponin I and N terminal of prohormone brain natriuretic peptide (tertiary end points) by 16% (95% CI, 8-23) and 18% (95% CI, 11-25), respectively. The incidence of serious adverse events (29.5% versus 28.5%; rate ratio, 1.07; 95% CI, 0.75-1.53), nonserious adverse reactions (36.7% versus 28.0%; rate ratio, 1.35; 95% CI, 0.96-1.90), and potassium ≥5.5 mmol/L (32% versus 24%, P=0.10) was not significantly different between randomized groups.
Conclusions: Over 12 months, sacubitril/valsartan has similar effects on kidney function and albuminuria to irbesartan, but it has the additional effect of lowering blood pressure and cardiac biomarkers in people with chronic kidney disease.
Clinical Trial Registration: URL: http://www.isrctn.com . Unique identifier: ISRCTN11958993.
Comment in: Circulation. 2018 Oct 9;138(15):1515-1518. (PMID: 30354525)
