eprintid: 10135686 rev_number: 12 eprint_status: archive userid: 608 dir: disk0/10/13/56/86 datestamp: 2021-10-05 15:25:16 lastmod: 2021-10-05 15:25:16 status_changed: 2021-10-05 15:25:16 type: article metadata_visibility: show creators_name: McMurray, JJV creators_name: Wheeler, DC creators_name: Stefánsson, BV creators_name: Jongs, N creators_name: Postmus, D creators_name: Correa-Rotter, R creators_name: Chertow, GM creators_name: Hou, FF creators_name: Rossing, P creators_name: Sjöström, CD creators_name: Solomon, SD creators_name: Toto, RD creators_name: Langkilde, AM creators_name: Heerspink, HJL creators_name: DAPA-CKD Trial Committees and Investigators, title: Effects of Dapagliflozin in Patients With Kidney Disease, With and Without Heart Failure ispublished: inpress divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G93 keywords: SGLT2 inhibitor, cardiovascular disease, chronic kidney disease, dapagliflozin, heart failure note: This is an Open Access article published under a Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). abstract: OBJECTIVES: The purpose of this paper was to investigate the effects of dapagliflozin in chronic kidney disease (CKD) patients, with and without heart failure (HF). BACKGROUND: Patients with CKD, with and without type 2 diabetes, were enrolled in the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial. Some patients had HF at baseline. METHODS: A total of 4,304 participants were randomized to dapagliflozin 10 mg daily or placebo. The primary composite endpoint was ≥50% decline in estimated glomerular filtration rate, end-stage kidney disease, or kidney/cardiovascular death. Secondary endpoints were a kidney composite (primary endpoint minus cardiovascular death), the composite of cardiovascular death/HF hospitalization, and all-cause death. Analysis of outcomes according to HF history was prespecified. RESULTS: HF patients (n = 468; 11%) were older and had more coronary disease, atrial fibrillation, and type 2 diabetes. Mean estimated glomerular filtration rate was similar in patients with and without HF. Rates of HF hospitalization/cardiovascular death and death from any cause were higher in HF patients, but the secondary kidney failure outcome occurred at the same rate in people with and without HF. Dapagliflozin reduced the risk of the primary outcome equally in patients with HF (HR: 0.58 [95% CI: 0.37-0.91]) and without HF (HR: 0.62 [95% CI: 0.51-0.75]) (P interaction = 0.59). The proportional risk-reductions were similar in patients with and without HF for the cardiovascular death/HF hospitalization composite (HR: 0.68 [95% CI: 0.44-1.05] vs HR: 0.70 [95% CI: 0.51-0.97], respectively; P interaction = 0.90), and all-cause death (HR: 0.56 [95% CI: 0.34-0.93] vs HR: 0.73 [95% CI: 0.54-0.97], respectively; P interaction = 0.39), although absolute risk reductions were larger in HF patients. Adverse event rates were low and did not differ among patients with or without HF. CONCLUSIONS: Dapagliflozin reduced the risk of kidney failure and cardiovascular death/HF hospitalization and prolonged survival in CKD patients with or without type 2 diabetes, independently of history of HF. (A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease [DAPA-CKD]; NCT03036150). date: 2021-08-23 date_type: published official_url: https://doi.org/10.1016/j.jchf.2021.06.017 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1890592 doi: 10.1016/j.jchf.2021.06.017 pii: S2213-1779(21)00334-6 lyricists_name: Wheeler, David lyricists_id: DWHEE12 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: JACC: Heart Failure event_location: United States citation: McMurray, JJV; Wheeler, DC; Stefánsson, BV; Jongs, N; Postmus, D; Correa-Rotter, R; Chertow, GM; ... DAPA-CKD Trial Committees and Investigators; + view all <#> McMurray, JJV; Wheeler, DC; Stefánsson, BV; Jongs, N; Postmus, D; Correa-Rotter, R; Chertow, GM; Hou, FF; Rossing, P; Sjöström, CD; Solomon, SD; Toto, RD; Langkilde, AM; Heerspink, HJL; DAPA-CKD Trial Committees and Investigators; - view fewer <#> (2021) Effects of Dapagliflozin in Patients With Kidney Disease, With and Without Heart Failure. JACC: Heart Failure 10.1016/j.jchf.2021.06.017 <https://doi.org/10.1016/j.jchf.2021.06.017>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10135686/1/1-s2.0-S2213177921003346-main.pdf