Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes

2型糖尿?。阂琅亮袃?、心血管轉(zhuǎn)歸和死亡

The effects of empagliflozin, an inhibitor of sodium–glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.

依帕列凈是一種鈉離子-葡萄糖協(xié)同轉(zhuǎn)運(yùn)蛋白2抑制劑。對于高心血管風(fēng)險(xiǎn)的2型糖尿病患者，該藥物聯(lián)合常規(guī)治療對心血管疾病風(fēng)險(xiǎn)和死亡風(fēng)險(xiǎn)的影響仍然未知。

We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina.

我們隨機(jī)招募了2型糖尿病患者參與本研究，所有受試者每天服用10 mg或25 mg的依帕列凈或安慰劑。研究的主要復(fù)合終點(diǎn)為心因性死亡、非致死性心肌梗塞或非致死性腦卒中，相關(guān)結(jié)果通過比較依帕列凈組和安慰劑組之間的差異得出。次要研究終點(diǎn)為主要終點(diǎn)+不穩(wěn)定型心絞痛住院。

A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P=0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P=0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events.

共計(jì)7020名患者納入本研究（中位觀察時(shí)間3.1年）。依帕列凈組的4687名受試者中，共有490人達(dá)到研究終點(diǎn)（10.5%），而安慰劑組為282人/2333人（12.1%）。兩個(gè)組別之間的心肌梗塞或腦卒中發(fā)生率并無明顯差異，但依帕列凈組的下列幾個(gè)指標(biāo)明顯更低：心因性死亡率（3.7%, vs. 5.9%；相對危險(xiǎn)降低率38%）、心衰入院率（2.7%和4.1%；相對危險(xiǎn)降低率35%）、全因死亡率（5.7%和8.3%；相對危險(xiǎn)降低率32%）。次要研究終點(diǎn)并無顯著差異。依帕列凈組受試者的生殖道感染風(fēng)險(xiǎn)更高，但其余不良事件發(fā)生率并無差異。

Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.

對于高心血管風(fēng)險(xiǎn)的2型糖尿病患者而言，常規(guī)藥物治療聯(lián)合依帕列凈可降低主要心血管復(fù)合終點(diǎn)風(fēng)險(xiǎn)和全因死亡風(fēng)險(xiǎn)。

參考文獻(xiàn)

Zinman, B., et al., Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. New England Journal of Medicine, 2015. 373(22): p. 2117-2128.