@article{discovery10122821,
           pages = {1735--1749},
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
          volume = {143},
         journal = {Circulation},
            year = {2021},
           title = {Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights from the CREDENCE Trial},
          number = {18},
           month = {May},
        keywords = {Canagliflozin, SGLT2 inhibitors, kidney outcomes},
          author = {Ye, N and Jardine, MJ and Oshima, M and Hockham, C and Heerspink, HJL and Agarwal, R and Bakris, G and Schutte, AE and Arnott, C and Chang, TI and G{\'o}rriz, JL and Cannon, CP and Charytan, DM and de Zeeuw, D and Levin, A and Mahaffey, KW and Neal, B and Pollock, C and Wheeler, DC and Di Tanna, GL and Cheng, H and Perkovic, V and Neuen, BL},
        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 {$\ge$}130/80 mmHg while receiving {$\ge$}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 {$\ge$}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 {$\ge$}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 {$\ge$}0.35), as were effects on other key kidney, cardiovascular and safety outcomes. CONCLUSION:},
             url = {https://doi.org/10.1161/CIRCULATIONAHA.120.048740}
}