Abstract 4536: Coronary Plaque is Stabilized by Daily Use of Oral Nicorandil Independent of Statin-use in Patients With Stable Angina Pectoris
Background: The impact of nicorandil in angina (IONA) trial demonstrated that nicorandil reduced future cardiovascular events in patients with stable angina. We assessed the hypothesis that nicorandil had a beneficial effect on the development of atherosclerotic lesion formation and coronary plaque characterization.
Methods and Results: Preintervention intravascular ultrasound-Virtual Histology (IVUS-VH) was performed prospectively in 65 coronary vessels in consecutive 65 patients with stable angina pectoris. The morphological distribution of plaque was evaluated up to a total length of 60 mm per coronary vessel. There were not significant differences regarding coronary risk factors such as blood pressure, hemoglobin A1c, low- and high-density lipoprotein cholesterol levels between nicorandil group (n=16) and non-nicorandil group (n=49). However, nicorandil group demonstrated a greater %fibrous tissue (68±10 vs 62±11%, P=0.04) and a lower %necrotic core (NC) tissue (11±7 vs 16±10%, P=0.04) compared with non-nicorandil group although external elastic membrane and plaque volumes were comparable. Multiple regression analyses including all clinical variables revealed that %NC tissue (P=0.045) was negatively and %fibrous tissue (P=0.026) was positively associated with the use of nicorandil independent of statin-use. We also analyzed the effect of chronic nicorandil treatment on atherosclerotic lesion formation in experimental murine model of atherosclerosis. ApoE deficient mice were maintained on an atherogenic western diet and received nicorandil (15 mg/kg/day) (n=5) or vehicle (n=5) for 8 weeks. Body weight, blood pressure and serum lipid profiles were unaffected, but atherosclerotic lesion area was significantly reduced in ApoE deficient mice treated with nicorandil (18.4±1.7 vs 24.5±2.9%, P=0.049). Quantitative RT-PCR revealed 22.3% decreased in expression of CHOP, the endoplasmic reticulum stress effecter, in atherosclerotic lesion by nicorandil treatment (P=0.032).
Conclusions: IVUS-VH may help to explain missing link between the use of nicorandil and coronary plaque morphology. Nicorandil may provide a pleiotropic effect for coronary plaque stabilization by different mechanisms from statin treatment.