University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, the Netherlands.
JAMA. 2014 Apr 16;311(15):1526-35. doi: 10.1001/jama.2014.3315.
Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function.
To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI).
DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013.
Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months.
The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure.
At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed.
Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting.
clinicaltrials.gov Identifier: NCT01217307.
二甲双胍治疗与糖尿病患者心肌梗死后的改善预后相关。在动物实验研究中，二甲双胍可保留左心室功能。
评估二甲双胍治疗对无糖尿病的 ST 段抬高型心肌梗死（STEMI）患者左心室功能保留的影响。
设计、地点和参与者：在荷兰格罗宁根大学医学中心，2011 年 1 月 1 日至 2013 年 5 月 26 日期间，对 380 例接受直接经皮冠状动脉介入治疗（PCI）的 STEMI 患者进行了一项双盲、安慰剂对照研究。
二甲双胍盐酸盐（500mg）（n=191）或安慰剂（n=189）每日 2 次，共 4 个月。
主要疗效指标为 4 个月时的左心室射血分数（LVEF），采用磁共振成像评估。次要疗效指标为 4 个月时的 N 端脑钠肽前体（NT-proBNP）浓度。次要疗效终点为 4 个月时的主要不良心脏事件（MACE；死亡、再梗死或靶病变血运重建的联合终点）发生率。
4 个月时，所有患者均存活，无失访。与安慰剂组（n=136）相比，二甲双胍组（n=135）的 LVEF 为 53.1%（95%CI，51.6%-54.6%）（P=0.10）。二甲双胍组的 NT-proBNP 浓度为 167ng/L（四分位距[IQR]，65-393ng/L），安慰剂组为 167ng/L（IQR，74-383ng/L）（P=0.66）。二甲双胍组有 6 例（3.1%）患者和安慰剂组有 2 例（1.1%）患者发生 MACE（P=0.16）。两组的肌酐浓度（79µmol/L [IQR，70-87µmol/L] vs 79µmol/L [IQR，72-89µmol/L]，P=0.61）和糖化血红蛋白（5.9% [IQR，5.6%-6.1%] vs 5.9% [IQR，5.7%-6.1%]，P=0.15）无显著差异。未观察到乳酸酸中毒病例。
在无糖尿病且 STEMI 并接受直接 PCI 的患者中，与安慰剂相比，使用二甲双胍并未导致 4 个月后的 LVEF 改善。本研究结果不支持在此类患者中使用二甲双胍。
clinicaltrials.gov 标识符：NCT01217307。
