eprintid: 263353 rev_number: 21 eprint_status: archive userid: 37347 dir: disk0/00/26/33/53 datestamp: 2022-01-27 15:39:27 lastmod: 2023-01-12 02:30:46 status_changed: 2022-01-27 15:39:27 type: article metadata_visibility: show sword_depositor: 37347 creators_name: Mc Causland, Finnian R. creators_name: Lefkowitz, Martin P. creators_name: Claggett, Brian creators_name: Packer, Milton creators_name: Senni, Michele creators_name: Gori, Mauro creators_name: Jhund, Pardeep S. creators_name: McGrath, Martina M. creators_name: Rouleau, Jean L. creators_name: Shi, Victor creators_name: Swedberg, Karl creators_name: Vaduganathan, Muthiah creators_name: Zannad, Faiez creators_name: Pfeffer, Marc A. creators_name: Zile, Michael creators_name: McMurray, John J.V. creators_name: Solomon, Scott D. creators_orcid: 0000-0003-4306-5317 creators_orcid: 0000-0002-6317-3975 title: Angiotensin‐neprilysin inhibition and renal outcomes across the spectrum of ejection fraction in heart failure ispublished: pub divisions: 25200000 full_text_status: public note: Novartis funded the study. abstract: Aims: Patients with heart failure are at higher risk of progression to end-stage renal disease (ESRD), regardless of ejection fraction (EF). We assessed the renal effects of angiotensin–neprilysin inhibition in a pooled analysis of 13 195 patients with heart failure with reduced and preserved EF. Methods and results: We combined data from PARADIGM-HF (EF ≤40%; n = 8399) and PARAGON-HF (EF ≥45%; n = 4796) in a pre-specified pooled analysis. We assessed the effect of treatment (sacubitril/valsartan vs. enalapril or valsartan) on a composite of either ≥50% reduction in estimated glomerular filtration rate (eGFR), ESRD, or death from renal causes, in addition to changes in eGFR slope. We assessed whether baseline renal function or EF modified the effect of therapy on renal outcomes. At randomization, eGFR was 68 ± 20 ml/min/1.73 m2 in PARADIGM-HF and 63 ± 19 ml/min/1.73 m2 in PARAGON-HF. The composite renal outcome occurred in 70 of 6594 patients (1.1%) in the sacubitril/valsartan group and in 123 of 6601 patients (1.9%) in the valsartan or enalapril group (hazard ratio 0.56, 95% confidence interval [CI] 0.42–0.75; p < 0.001). The mean eGFR change was −1.8 (95% CI −1.9 to −1.7) ml/min/1.73 m2/year for the sacubitril/valsartan group, compared with −2.4 (95% CI −2.5 to −2.2) ml/min/1.73 m2/year for the valsartan or enalapril group. The treatment effect on the composite renal endpoint was not modified by categories of baseline eGFR (p-interaction = 0.64), but was most pronounced in those with baseline EF between 30% and 60% (p-interaction = 0.001). Conclusions: In patients with heart failure, sacubitril/valsartan reduced the risk of serious adverse renal outcomes and slowed decline in eGFR, compared with valsartan or enalapril, independent of baseline renal function. date: 2022-09 date_type: published publication: European Journal of Heart Failure volume: 24 number: 9 publisher: Wiley pagerange: 1591-1598 id_number: 10.1002/ejhf.2421 refereed: TRUE issn: 1388-9842 copyright_holders: Copyright © 2022 John Wiley and Sons Ltd prior: First published in European Journal of Heart Failure 24(9): 1591-1598 repro: Reproduced in accordance with the copyright policy of the publisher uniqueid: glaseprints:2022-263353 issn_online: 1879-0844 pubmed_id: 34989105 euro_pubmed_id: 34989105 hoa_compliant: 511 hoa_emb_len: 12 hoa_ref_pan: AB hoa_date_acc: 2022-01-03 hoa_date_pub: 2022-01-05 hoa_date_foa: 2023-01-11 hoa_version_fcd: AM hoa_exclude: FALSE hoa_gold: FALSE oa_research_materials_ack: No citation: Mc Causland, F. R. et al. (2022) Angiotensin‐neprilysin inhibition and renal outcomes across the spectrum of ejection fraction in heart failure. European Journal of Heart Failure , 24(9), pp. 1591-1598. (doi: 10.1002/ejhf.2421 ) (PMID:34989105) document_url: https://eprints.gla.ac.uk/263353/3/263353.pdf document_url: https://eprints.gla.ac.uk/263353/2/263353Suppl.pdf