Two-year follow-up of 4 months metformin treatment vs. placebo in ST-elevation myocardial infarction: data from the GIPS-III RCT

Minke H T Hartman, Jake K B Prins, Remco A J Schurer, Erik Lipsic, Chris P H Lexis, Anouk N A van der Horst-Schrivers, Dirk J van Veldhuisen, Iwan C C van der Horst, Pim van der Harst, Minke H T Hartman, Jake K B Prins, Remco A J Schurer, Erik Lipsic, Chris P H Lexis, Anouk N A van der Horst-Schrivers, Dirk J van Veldhuisen, Iwan C C van der Horst, Pim van der Harst

Abstract

Objectives: Preclinical and clinical studies suggested cardioprotective effects of metformin treatment. In the GIPS-III trial, 4 months of metformin treatment did not improve left ventricular ejection fraction in patients presenting with ST-elevation myocardial infarction (STEMI). Here, we report the 2-year follow-up results.

Methods: Between January 2011 and May 2013, 379 STEMI patients without diabetes undergoing primary percutaneous coronary intervention were randomized to a 4-month treatment with metformin (500 mg twice daily) (N = 191) or placebo (N = 188) in the University Medical Center Groningen. Two-year follow-up data was collected to determine its effect on predefined secondary endpoints: the incidence of major adverse cardiac events (MACE), its individual components, all-cause mortality, and new-onset diabetes.

Results: For all 379 patients all-cause mortality data were available. For seven patients (2%) follow-up data on MACE was limited, ranging from 129 to 577 days. All others completed the 2-year follow-up visit. Incidence of MACE was 11 (5.8%) in metformin and 6 (3.2%) in placebo treated patients [hazard ratio (HR) 1.84, confidence interval (CI) 0.68-4.97, P = 0.22]. Three patients died in the metformin group and one in the placebo treatment group. Individual components of MACE were also comparable between both groups. New-onset diabetes mellitus was 34 (17.8%) in metformin and 32 (17.0%) in placebo treated patients (odds ratio 1.15, CI 0.66-1.98, P = 0.84). After multivariable adjustment the incidence of MACE was comparable between the treatment groups (HR 1.02, CI 0.10-10.78, P = 0.99).

Conclusions: Four months metformin treatment initiated at the time of hospitalization in STEMI patients without diabetes did not exert beneficial long-term effects.

Trial registration: clinicaltrials.gov Identifier: NCT01217307.

Keywords: Acute myocardial infarction; Diabetes; Heart failure; Metformin; Percutaneous coronary intervention.

Conflict of interest statement

Ethical approval

The GIPS-III study was approved by the institutional ethics committee and was in accordance with the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

The GIPS-III randomized controlled clinical trial was supported by Grant no. 95103007, from ZonMw, the Netherlands Organization for Health Research and Development, The Hague, the Netherlands.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curve representing MACE-free survival during 2-year follow-up in the metformin and placebo treatment groups. MACE-free survival was not significantly different between the groups (Log-rank test P = 0.22)
Fig. 2
Fig. 2
Median NT pro-BNP levels during 2-year follow-up in the metformin treatment and placebo treatment group. Levels were not significantly different between the groups (linear mixed effects P = 0.35)

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