Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:74

Article

Kotecha, Dipak^1,2  Gill, Simrat K.¹  Flather, Marcus D.³  Holmes, Jane⁴  Packer, Milton⁵  Rosano, Giuseppe^6,7  Boehm, Michael⁸  McMurray, John J. V.^9,10  Wikstrand, John¹¹  Anker, Stefan D.¹²  van Veldhuisen, Dirk J.¹³  Manzano, Luis¹⁴  von Lueder, Thomas G.^2,15  Rigby, Alan S.¹⁶  Andersson, Bert^17,18  Kjekshus, John^19,20  Wedel, Hans²¹  Ruschitzka, Frank²²  Cleland, John G. F.²³  Damman, Kevin¹³  Redon, Josep²⁴  Coats, Andrew J. S.⁷ 

[1] Univ Birmingham, Inst Cardiovasc Sci, Birmingham, W Midlands, England

[2] Monash Univ, Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic, Australia

[3] Univ East Anglia, Fac Med & Hlth Sci, Norwich Med Sch, Norwich, Norfolk, England

[4] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Ctr Stat Med, Oxford, England

[5] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX USA

[6] St Georges Univ London, Cardiovasc & Cell Sci Inst, London, England

[7] IRCCS San Raffaele Pisana, Dept Med Sci, Rome, Italy

[8] Univ Klinikum Saarlandes, Kardiol Angiol & Internist Intens Med, Homburg, Germany

[9] Univ Glasgow, Robertson Inst Biostat, Glasgow, Lanark, Scotland

[10] Univ Glasgow, Clin Trials Unit, Glasgow, Lanark, Scotland

[11] Gothenburg Univ, Sahlgrenska Acad, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden

[12] Charite Campus Virchow Klinikum, Dept Cardiol, Berlin, Germany

[13] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Rb Groningen, Netherlands

[14] Univ Alcala IRYCIS, Hosp Univ Ramon & Cajal, Dept Internal Med, Plaza San Diego, Madrid, Spain

[15] Oslo Univ Hosp, Dept Cardiol, Oslo, Norway

[16] Univ Hull, Fac Hlth Sci, Hull York Med Sch, Kingston Upon Hull, Yorks, England

[17] Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden

[18] Gothenburg Univ, Gothenburg, Sweden

[19] Univ Oslo, Rikshosp Univ Hosp, Oslo, Norway

[20] Univ Oslo, Fac Med, Oslo, Norway

[21] Univ Gothenburg, Sahlgrenska Acad, Hlth Metr, Gothenburg, Sweden

[22] Univ Spital Zurich, Klin Kardiol, Zurich, Switzerland

[23] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland

[24] INCLIVA Biomed Res Inst, Valencia, Spain

关键词: beta-blockers;    heart failure;    mortality;    renal impairment;   

DOI  :  10.1016/j.jacc.2019.09.059

来源: Elsevier

【 摘 要 】

BACKGROUND Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m(2); 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m(2), and 2,286 (13.7%) 30 to 44 ml/min/1.73 m(2). Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m(2) lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m(2) (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m(2) (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m(2)) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction. (C) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

【 授权许可】

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