Revista Española de Cardiología (English Edition) Revista Española de Cardiología (English Edition)
Rev Esp Cardiol. 2018;71:917-25 - Vol. 71 Num.11 DOI: 10.1016/j.rec.2017.12.005

In Vivo Evaluation of the Synergic Effect of Metformin and mTOR Inhibitors on the Endothelial Healing of Drug-eluting Stents in Diabetic Patients

Héctor Cubero-Gallego a, Rafael Romaguera a,, Josep Gómez-Lara a, Joan A. Gómez-Hospital a, Manel Sabaté b, Eduardo Pinar c, Montserrat Gracida a, Gerard Roura a, José L. Ferreiro a, Luis Teruel a, Cristian Tebé-Codorni d, Pilar Jiménez-Quevedo e, Eduard Montanya f, Fernando Alfonso g, Ángel Cequier a

a Departamento de Cardiología Intervencionista, Hospital Universitario de Bellvitge, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
b Departamento de Cardiología Intervencionista, Hospital Clínic de Barcelona, Barcelona, Spain
c Departamento de Cardiología Intervencionista, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
d Departamento de Estadística, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
e Departamento de Cardiología Intervencionista, Hospital Clínico San Carlos, Madrid, Spain
f Departamento de Endocrinología, Hospital Universitario de Bellvitge, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), L’Hospitalet de Llobregat, Barcelona, Spain
g Departamento de Cardiología Intervencionista, Hospital Universitario de La Princesa, Madrid, Spain

Keywords

Metformin. Drug-eluting stents. Diabetes mellitus.

Abstract

Introduction and objectives

Recent animal studies have shown metformin (MF) to impair endothelialization of drug-eluting stents (DES). The aim of this study was to evaluate the effect of MF on the healing of DES in human coronary arteries of patients with diabetes mellitus by optical coherence tomography (OCT).

Methods

The RESERVOIR trial randomized 116 lesions in 112 patients with diabetes mellitus to amphilimus- or everolimus-eluting stents and included mandatory OCT at 9 months of follow-up. Patients were divided in 3 groups according to the glucose-lowering agents received: a) no MF; b) MF in noninsulin treated patients, and c) MF in insulin-treated patients. The primary safety endpoint was the rate of uncovered stents.

Results

Seventeen patients with 19 lesions did not receive MF, whereas MF was administered to 53 noninsulin treated patients (54 lesions) and 28 insulin-treated patients (28 lesions). Baseline characteristics were comparable, although noninsulin treated patients who received MF had better glycemic control (P < .01). By OCT, rates of uncovered struts were comparable between groups (3.07 ± 4.80% vs 2.23 ± 4.73% vs 3.43 ± 6.69%, respectively; P = .48). Multivariate models confirmed that MF had no effect on the healing of DES (OR, 1.49, 95%CI, 0.71-3.08; P = .29). Similarly, quantitative angiography showed no effect of MF on late lumen loss, whereas patients treated with exogenous insulin had greater late lumen loss (P = .02).

Conclusions

Metformin use does not impair endothelial healing of DES in patients with both insulin- and noninsulin-treated diabetes mellitus. According to these results, MF should not be discouraged in these patients.

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1885-5857/© 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved

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