eprintid: 10122821 rev_number: 21 eprint_status: archive userid: 608 dir: disk0/10/12/28/21 datestamp: 2021-03-03 13:01:06 lastmod: 2022-04-25 13:33:51 status_changed: 2021-03-03 13:01:06 type: article metadata_visibility: show creators_name: Ye, N creators_name: Jardine, MJ creators_name: Oshima, M creators_name: Hockham, C creators_name: Heerspink, HJL creators_name: Agarwal, R creators_name: Bakris, G creators_name: Schutte, AE creators_name: Arnott, C creators_name: Chang, TI creators_name: Górriz, JL creators_name: Cannon, CP creators_name: Charytan, DM creators_name: de Zeeuw, D creators_name: Levin, A creators_name: Mahaffey, KW creators_name: Neal, B creators_name: Pollock, C creators_name: Wheeler, DC creators_name: Di Tanna, GL creators_name: Cheng, H creators_name: Perkovic, V creators_name: Neuen, BL title: Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights from the CREDENCE Trial ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G93 keywords: Canagliflozin, SGLT2 inhibitors, kidney outcomes note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. abstract: BACKGROUND: People with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) experience a high burden of hypertension but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population is uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP lowering therapy is also unknown. METHODS: the CREDENCE trial randomized people with T2DM and CKD to canagliflozin or placebo. Post-hoc, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mmHg while receiving ≥3 classes of BP lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups. RESULTS: The trial included 4,401 participants of whom 3,361 (76.4%) had baseline systolic BP ≥130 mmHg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50mmHg (95% CI, -4.27 to -2.72), an effect maintained over the duration of the trial, with similar reductions across BP and BP lowering therapy subgroups (all P-interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP lowering agents during the trial (HR 0.68, 95% CI 0.61-0.75). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death due to kidney or cardiovascular disease (HR 0.70, 95% CI 0.59-0.82) was consistent across BP and BP lowering therapy subgroups (all P-interaction ≥0.35), as were effects on other key kidney, cardiovascular and safety outcomes. CONCLUSION: date: 2021-05-04 date_type: published official_url: https://doi.org/10.1161/CIRCULATIONAHA.120.048740 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1847974 doi: 10.1161/CIRCULATIONAHA.120.048740 lyricists_name: Wheeler, David lyricists_id: DWHEE12 actors_name: Wheeler, David actors_id: DWHEE12 actors_role: owner full_text_status: public publication: Circulation volume: 143 number: 18 pagerange: 1735-1749 event_location: United States citation: Ye, N; Jardine, MJ; Oshima, M; Hockham, C; Heerspink, HJL; Agarwal, R; Bakris, G; ... Neuen, BL; + view all <#> Ye, N; Jardine, MJ; Oshima, M; Hockham, C; Heerspink, HJL; Agarwal, R; Bakris, G; Schutte, AE; Arnott, C; Chang, TI; Górriz, JL; Cannon, CP; Charytan, DM; de Zeeuw, D; Levin, A; Mahaffey, KW; Neal, B; Pollock, C; Wheeler, DC; Di Tanna, GL; Cheng, H; Perkovic, V; Neuen, BL; - view fewer <#> (2021) Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights from the CREDENCE Trial. Circulation , 143 (18) pp. 1735-1749. 10.1161/CIRCULATIONAHA.120.048740 <https://doi.org/10.1161/CIRCULATIONAHA.120.048740>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10122821/1/379911_0_merged_1590387662.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/10122821/7/379911_0_unknown_upload_4950399_qnvnvl.pdf