Evaluación del efecto sinérgico de la metformina y los inhibidores mTOR sobre la endotelización de los stents farmacoactivos en pacientes diabéticos / In vivo evaluation of the synergic effect of metformin and mTOR inhibitors on the endothelial healing of drug-eluting stents in diabetic patients

Introducción y objetivos: Estudios recientes en animales han demostrado que la metformina (MF) perjudica la endotelización de los stents farmacoactivos (SFA). Se evaluó el efecto de la MF en el recubrimiento neointimal de los SFA en pacientes diabéticos por tomografía de coherencia óptica (OCT). Métodos: El ensayo RESERVOIR aleatorizó 116 lesiones en 112 pacientes con diabetes mellitus a stents liberadores de amphilimus o everolimus, a los que se realizó una OCT a los 9 meses. Los pacientes se dividieron en 3 grupos según el tratamiento hipoglucemiante recibido: a) no MF; b) MF sin insulina, y c) MF con insulina. El objetivo primario fue el porcentaje de struts no recubiertos. Resultados: Diecisiete pacientes (19 lesiones) al grupo sin MF; 53 pacientes (54 lesiones) al grupo MF sin insulina y 28 pacientes (28 lesiones) al grupo MF con insulina. Las características basales fueron comparables, aunque los pacientes del grupo MF sin insulina tuvieron un mejor control glucémico (p < 0,01). Por OCT la frecuencia relativa de struts no recubiertos fue comparable entre grupos (3,07 ± 4,80% frente a 2,23 ± 4,73% frente a 3,43 ± 6,69% respectivamente, p = 0,48). El análisis multivariante confirmó que la MF no altera el recubrimiento de los SFA (OR = 1,49; IC95%, 0,71-3,08, p = 0,29). La angiografía cuantitativa tampoco mostró efecto de la MF sobre la pérdida luminal tardía, mientras que el tratamiento con insulina si se asoció a una mayor pérdida luminal tardía (p = 0,02). Conclusiones: El uso de MF no perjudica el recubrimiento neointimal de los SFA en diabéticos independientemente de que reciban o no tratamiento con insulina. De acuerdo a nuestros resultados, el uso de MF parece no estar desaconsejado en estos pacientes

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

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

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.