Long-term isosorbide mononitrate treatment impairs endothelial function in patients with coronary artery disease

Sustained use of nitrates is associated with adverse effects on vascular function by increasing oxidative stress. It remains unclear whether oxidative stress impairs endothelial function in patients with coronary artery disease (CAD) during long-term oral use of nitrates. The purpose of this study was to evaluate the effects of long-term isosorbide mononitrate (ISMN) treatment on oxidative stress and endothelial function in patients with CAD.

In this prospective, double-blinded, placebo-controlled, randomized, single-center study, 60 patients were assigned to treatment with ISMN 20 mg retarded release orally twice per day (ISMN group, n=30) or placebo (control group, n=30) for 1 year. The primary endpoint was the change in brachial artery endothelium-dependent dilation [flow-mediated dilation (FMD)] from baseline to follow-up. Furthermore, serum superoxide dismutase, malondialdehyde, and hypersensitive C-reactive protein levels were also measured at baseline and follow-up.

The FMD decreased significantly (from 5.97±2.88 to 5.33±2.56%) in the ISMN group, whereas it increased from 6.27±3.23 to 6.96±2.84% in the control group after treatment for 1 year. There was a significant difference in the changes in FMD when the two groups were compared (-0.64±1.83 vs. 0.69±1.77%, P=0.006). There were no significant changes in serum superoxide dismutase, malondialdehyde, and hypersensitive C-reactive protein levels in the two groups.

Long-term ISMN treatment may impair endothelial function in patients with CAD.