The George Institute for Global Health UNSW Sydney Sydney Australia.
Department of Cardiology, Xinqiao Hospital Army Military Medical University Chongqing China.
J Am Heart Assoc. 2022 Aug 16;11(16):e025045. doi: 10.1161/JAHA.121.025045. Epub 2022 Aug 5.
Background The sodium-glucose cotransporter 2 inhibitor canagliflozin reduced the risk of first cardiovascular composite events in the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial. In this post hoc analysis, we evaluated the effect of canagliflozin on total (first and recurrent) cardiovascular events. Methods and Results The CREDENCE trial compared canagliflozin or matching placebo in 4401 patients with type 2 diabetes, albuminuria, and estimated glomerular filtration rate of 30 to <90 mL/min per 1.73 m, over a median of 2.6 years. The primary outcome was analyzed as a composite of any cardiovascular event including myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, and cardiovascular death. Negative binomial regression models were used to assess the effect of canagliflozin on the net burden of cardiovascular events. During the trial, 634 patients had 883 cardiovascular events, of whom 472 (74%) had just 1 cardiovascular event and 162 (26%) had multiple cardiovascular events. Canagliflozin reduced first cardiovascular events by 26% (hazard ratio, 0.74 [95% CI, 0.63-0.86]; <0.001) and total cardiovascular events by 29% (incidence rate ratio, 0.71 [95% CI, 0.59-0.86]; <0.001). The absolute risk difference per 1000 patients treated over 2.5 years was -44 (95% CI, -67 to -21) first cardiovascular events and -73 (95% CI, -114 to -33) total events. Conclusions Canagliflozin reduced cardiovascular events, with a larger absolute benefit for total cardiovascular than first cardiovascular events. These findings provide further support for the benefit of continuing canagliflozin therapy after an initial event to prevent recurrent cardiovascular events. Registration Information URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02065791.
钠-葡萄糖协同转运蛋白 2 抑制剂卡格列净可降低 CREDENCE（卡格列净和糖尿病肾病中的肾脏事件临床评估）试验中首次心血管复合事件的风险。在此事后分析中，我们评估了卡格列净对总（首次和复发）心血管事件的影响。
CREDENCE 试验将卡格列净或匹配的安慰剂在 4401 例 2 型糖尿病、白蛋白尿和估计肾小球滤过率为 30 至 <90 ml/min/1.73 m 的患者中进行比较，中位随访时间为 2.6 年。主要结局分析为任何心血管事件的复合结局，包括心肌梗死、卒中和心力衰竭住院、不稳定型心绞痛住院以及心血管死亡。使用负二项式回归模型评估卡格列净对心血管事件净负担的影响。在试验期间，634 例患者发生 883 例心血管事件，其中 472 例（74%）仅发生 1 例心血管事件，162 例（26%）发生多次心血管事件。卡格列净可使首次心血管事件减少 26%（风险比，0.74[95%CI，0.63-0.86]；<0.001），总心血管事件减少 29%（发生率比，0.71[95%CI，0.59-0.86]；<0.001）。每 1000 例患者治疗 2.5 年的绝对风险差异为-44（95%CI，-67 至-21）首次心血管事件和-73（95%CI，-114 至-33）总事件。
卡格列净减少了心血管事件，且总心血管事件的绝对获益大于首次心血管事件。这些发现进一步支持在首次心血管事件后继续使用卡格列净治疗以预防复发心血管事件的获益。
