The George Institute for Global Health (N.Y., M.J.J., M.O., C.H., A.E.S., C.A., B.N., D.C.W., G.L.D.T., V.P., B.L.N.), University of New South Wales, Sydney, Australia.
Renal Division, Beijing Anzhen Hospital, Capital Medical University, China (N.Y., H.C.).
Circulation. 2021 May 4;143(18):1735-1749. doi: 10.1161/CIRCULATIONAHA.120.048740. Epub 2021 Feb 8.
People with type 2 diabetes and chronic kidney disease experience a high burden of hypertension, but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population are uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP-lowering therapy is also unknown.
The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) randomized people with type 2 diabetes and chronic kidney disease to canagliflozin or placebo. In a post hoc analysis, 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 mm Hg while receiving ≥3 classes of BP-lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups.
The trial included 4401 participants, of whom 3361 (76.4%) had baseline systolic BP ≥130 mm Hg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50 mm Hg (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 interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP-lowering agents during the trial (hazard ratio, 0.68 [95% CI, 0.61-0.75]). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death caused by kidney or cardiovascular disease (hazard ratio, 0.70 [95% CI, 0.59-0.82]) was consistent across BP and BP-lowering therapy subgroups (all interaction ≥0.35), as were effects on other key kidney, cardiovascular, and safety outcomes.
In people with type 2 diabetes and chronic kidney disease, canagliflozin lowers systolic BP across all BP-defined subgroups and reduces the need for additional BP-lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP-lowering therapy in people with chronic kidney disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.
2 型糖尿病合并慢性肾病患者的高血压负担较重，但坎格列净对该人群血压降低的幅度和一致性尚不确定。坎格列净对肾脏和心血管结局的影响是否因基线血压或降压治疗而有所不同也尚不清楚。
CREDENCE 试验（伴有明确肾脏疾病的 2 型糖尿病患者中的卡格列净与肾脏事件的临床评估）将 2 型糖尿病合并慢性肾病患者随机分配至坎格列净组或安慰剂组。在一项事后分析中，我们根据基线收缩压、降压药种类数和明显治疗抵抗性高血压的病史（接受包括利尿剂在内的 3 种以上降压药物治疗时血压≥130/80mmHg），研究了坎格列净对收缩压的影响。我们还评估了这些亚组之间对临床结局的影响是否存在差异。
该试验共纳入 4401 名参与者，其中 3361 名（76.4%）基线收缩压≥130mmHg，1371 名（31.2%）有难治性高血压。在第 3 周时，坎格列净降低收缩压 3.50mmHg（95%CI，-4.27 至-2.72），这一效果在整个试验期间得以维持，且在各血压和降压治疗亚组中降低幅度相似（所有交互作用 P≥0.05）。坎格列净还减少了试验期间开始使用额外降压药物的需求（风险比，0.68[95%CI，0.61-0.75]）。坎格列净对肾衰竭、血清肌酐翻倍或因肾脏或心血管疾病导致的死亡（风险比，0.70[95%CI，0.59-0.82]）的影响在各血压和降压治疗亚组中均一致（所有交互作用 P≥0.35），其他关键肾脏、心血管和安全性结局也有类似的影响。
在 2 型糖尿病合并慢性肾病患者中，坎格列净可降低所有基于血压定义的亚组的收缩压，并减少对额外降压药物的需求。这些发现支持坎格列净用于靶器官保护和作为慢性肾病患者降压治疗的辅助药物。
