Effects of metformin therapy on COronary endothelial DYsfunction in prediabetic patients With stable angina and Non Obstructive Coronary Artery Stenosis: The CODYCE Multicenter Prospective Study

Diabetes Care. 2019 Feb 22. pii: dc182356.

Effects of metformin therapy on COronary endothelial DYsfunction in prediabetic patients With stable angina and Non Obstructive Coronary Artery Stenosis: The CODYCE Multicenter Prospective Study.

Sardu C1, Paolisso P2, Sacra C3, Mauro C4, Minicucci F4, Portoghese M5, Rizzo MR2, Barbieri M2, Sasso FC2, D’Onofrio N6, Balestrieri ML6, Calabrò P7, Paolisso G2, Marfella R2.

Author information

1
Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania “Luigi Vanvitelli,” Naples, Italy drsarducele@gmail.com.
2
Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania “Luigi Vanvitelli,” Naples, Italy.
3
Department of Cardiovascular Diseases, John Paul II Research and Care Foundation, Campobasso, Italy.
4
Department of Cardiovascular Diseases, Antonio Cardarelli Hospital, Naples, Italy.
5
U.O.C. Division of Cardiovascular Surgery, Sassari Hospital, Sassari, Italy.
6
Department of Precision Medicine, University of Campania “Luigi Vanvitelli,” Naples, Italy.
7
Division of Clinical Cardiology, A.O.R.N. Sant’Anna e San Sebastiano, Caserta, Italy.

Abstract

OBJECTIVE:

To evaluate the effect of metformin therapy on coronary endothelial function and major adverse cardiac events (MACE) in patients with prediabetes with stable angina and nonobstructive coronary stenosis (NOCS).

RESEARCH DESIGN AND METHODS:

Metformin therapy may be needed to reduce coronary heart disease risk in patients with prediabetes. A total of 258 propensity score-matched (PSM) patients with stable angina undergoing coronary angiography were enrolled in the study. Data from 86 PSM subjects with normoglycemia (NG), 86 PSM subjects with prediabetes (pre-DM), and 86 PSM subjects with prediabetes treated with metformin (pre-DM metformin) were analyzed. During coronary angiography, NOCS was categorized by luminal stenosis <40% and fractional flow reserve >0.80. In addition, we assessed the endothelial function, measuring coronary artery diameter of left anterior descending coronary (LAD) at baseline and after the infusion of acetylcholine, by means of an intracoronary Doppler guide wire. MACE, as cardiac death, myocardial infarction, and heart failure, was evaluated at 24 months of follow-up.

RESULTS:

At baseline, NG patients had a lower percentage of LAD endothelial dysfunction compared with pre-DM patients (P < 0.05). The patients with pre-DM had a higher percentage of endothelial LAD dysfunction as compared to patients with pre-DM treated with metformin (P< 0.05). At the 24th month of follow-up, MACE was higher in pre-DM versus NG (P < 0.05). In pre-DM metformin patients, MACE was lower compared with pre-DM patients (P < 0.05).

CONCLUSIONS:

Metformin therapy may reduce the high risk of cardiovascular events in pre-DM patients by reducing coronary endothelial dysfunction.

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