Effect of Metformin on Renal Function After Primary Percutaneous Coronary Intervention in Patients Without Diabetes Presenting with ST-elevation Myocardial Infarction: Data from the GIPS-III Trial

Abstract

PurposeThe association between metformin use and renal function needs further to be elucidated since data are insufficient whether metformin affects renal function in higher risk populations such as after ST-elevation myocardial infarction (STEMI).MethodsWe studied 379 patients included in the GIPS-III trial in which patients without diabetes or renal dysfunction, who underwent primary percutaneous coronary interventions (PCI) for STEMI, were randomized to metformin 500 mg or placebo twice daily for four months. At baseline and at seven scheduled visits up to four months after PCI, estimated glomerular filtration rate (eGFR) was determined (2582 values). Contrast-induced acute kidney injury (CI-AKI) was defined as an increase in serum creatinine of ≥0.3 mg/dl or 25 % rise within 48 h after PCI.ResultsAt all visits, the mean eGFR was similar in patients randomized to metformin or placebo. Over the four month period, mixed-effect repeated-measures model analysis showed a least-squares mean ± standard error change in eGFR of -5.9 ± 0.8 ml/min/1.73 m2 in the metformin group and −7.1 ± 0.8 ml/min/1.73 m2 in the control group (P = 0.27 for overall interaction). The incidence of CI-AKI was 14.8 %; 29 (15.2 %) patients in the metformin group versus 27 (14.4 %) controls (P = 0.89). After adjustment for covariates, metformin treatment was not associated with CI-AKI (odds ratio: 0.96, 95%CI 0.52 − 1.75, P = 0.88).ConclusionWe conclude that initiation of metformin shortly after primary PCI has no adverse effect on renal function in patients without diabetes or prior renal impairment, further providing evidence of the safety of metformin use after myocardial infarction and subsequent contrast exposure.Electronic supplementary materialThe online version of this article (doi:10.1007/s10557-015-6618-1) contains supplementary material, which is available to authorized users.

Impact of continuation of metformin prior to elective coronary angiography on acute contrast nephropathy in patients with normal or mildly impaired renal functions

“…Zeller et al ( 25 ) reported that chronic metformin treatment prior to primary PCI had no significant impact on CIN, and there was a protective effect of metformin against CIN consistent with our results. In the GIPS III trial including 379 patients without diabetes and renal dysfunction, metformin treatment started shortly after primary PCI had no deleterious effect on renal functions, supporting the hypothesis of safe use of metformin in this patient population ( 26 ). The doses of metformin administered to both groups in our study were relatively low; thus, the unadaptation to the drug dosage to renal functions might influence renal outcomes.…”

Increasing metformin concentrations and its excretion in both rat and porcine ex vivo normothermic kidney perfusion model

“…Long-term metformin use of patients under normal circumstances and during acute illness was associated with mixed, but in all cases, limited effects on renal function. [43][44][45][46][47][48][49] This study has important clinical implications. Metformin is currently contraindicated in patients with significant renal dysfunction because of the risk of metformin accumulation and lactic acidosis.…”

Effect of continuous use of metformin on kidney function in diabetes patients with acute myocardial infarction undergoing primary percutaneous coronary intervention

“…The GIPS III trial has supported the idea that metformin is safe to use after STEMI and contrast agent exposure. Nondiabetic patients started metformin therapy within 3 h after the coronary intervention had no harmful effect on kidney functions [11]. In addition, a multi-centre observational study has shown that chronic metformin treatment before PCI has no significant effect on CI-AKI in T2DM patients with STEMI [2].…”

“…Because of the post-procedural risk-MALA and CI-AKI in diabetic patients submitted to PCI for STEMI, the guidelines are inconsistent on whether to continue metformin in patients undergoing PCI [7][8][9][10]. Currently, studies had concluded that initiation of metformin ≤ 3 h after primary PCI and chronic metformin therapy before primary PCI had no influence on CI-AKI in STEMI patients [2,11]. However, there is no clinical data about the continuation of metformin treatment during the primary PCI period in diabetic patients with STEMI, and the effects of metformin on the kidneys are still widely debated in patients exposed to contrast agents [12,13].…”