Background: In-stent restenosis results from neointimal tissue proliferation. L-arginine supplementation improves endothelial function and reduces neointimal formation after arterial injury in animals. The aim of the study was to assess the influence of L-arginine administration on neointimal proliferation after coronary stenting in human beings.
Methods: We performed a prospective, randomized, double-blinded, placebo-controlled study in 60 men without diabetes. L-arginine/placebo was administered intravenously 12 hours before percutaneous coronary intervention (200 mg/kg for 240 minutes), during the procedure (200 mg/kg for 240 minutes), and intracoronarily immediately before stent implantation (500 mg for 10 minutes), and it was followed by oral treatment for next 2 weeks (6.0 g/d). By quantitative coronary angiography, late lumen loss, and intravascular ultrasound, neointimal volume and percent neointimal volume were calculated after 7 months of follow-up to assess neointimal formation.
Results: There were no differences in baseline clinical or angiographic characteristics between the two groups. Intravenous infusion of L-arginine increased plasma L-arginine concentrations 6-fold compared with placebo (661 +/- 264 vs 107 +/- 71 mmol/L, P <.001). During the 2-week period of oral treatment with L-arginine there was a sustained, significant increase of plasma L-arginine level (150 +/- 50 vs 100 +/- 17, P <.001, 135 +/- 42 vs 89 +/- 27, P <.001, respectively, on days 7 and 14 in the L-arginine group vs placebo). However, at 7-month follow-up, there was no difference in neointimal formation measured both by quantitative coronary angiography and intravascular ultrasound between the study groups.
Conclusions: Chronic systemic L-arginine administration has no effect on neointimal formation after coronary stenting in human beings.