Effects of Long-term Nicorandil Administration on Endothelial Function, Inflammation, and Oxidative Stress in Patients Without Coronary Artery Disease

Abstract

Long-term administration of nicorandil has been shown to improve outcomes through cardioprotective effects in patients with coronary artery disease. To identify the mechanisms responsible for these effects, this study examined the impact of long-term nicorandil administration on endothelial function, systemic inflammatory markers, and oxidative stress in patients with cardiovascular risk factors. Fifty-three patients were assigned to receive either nicorandil therapy (15 mg/day; n = 26) (nicorandil group) or usual care (n = 27) (nonnicorandil group). All study participants underwent flow-mediated vasodilatation (FMD) of the brachial artery 1 month before treatment, just before treatment, and at 3, 6, and 12 months following treatment. At identical time points, serum levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL) and high-sensitivity C-reactive protein (hs-CRP) were collected. Compared with the nonnicorandil group, the nicorandil group demonstrated significantly increased FMD at 12 months, a finding not replicated for endothelium-independent vasodilatation with nitroglycerine. Analysis of biochemical markers revealed significantly reduced MAD-LDL levels in the nicorandil group at 12 months, as compared to slightly increased MAD-LDL levels in the nonnicorandil group. Significant reductions in hs-CRP levels were also noted at 6 and 12 months in the nicorandil group, while no change was found in the nonnicorandil group. Results demonstrated that long-term nicorandil therapy is associated with gradual improvements in endothelial function. Our findings also suggest that nicorandil treatment may result in cardiovascular protection through pleiotropic effects including reductions in oxidative injury and systemic inflammation.