Abstract 3920: Long-Term Nicorandil Therapy Reverses Left Ventricular Remodeling in Patients With Chronic Heart Failure: A Randomized Placebo-Controlled Study
Background: Nicorandil (NIC), a K-ATP channel opener with a nitrate-like action, is a potent vasodilator and has favorable hemodynamic effects in heart failure patients. While its cardio-protective properties in the setting of acute ischemia are well known, there is no information about the long-term effect of oral nicorandil therapy on left ventricular (LV) remodeling in patients with chronic heart failure (CHF).
Methods: We enrolled 22 mild to moderate CHF patients (NYHA class: 2.1±0.5, ischemic origin:73%) with radionuclide LV ejection fraction (LVEF) <40%. These patients were randomly assigned to receive NIC (30mg/day) or placebo for the initial 6 months in a double-blinded fashion. Thereafter, this study was opened and we prospectively followed up these patients for three years. At the entry, we measured LV end-diastolic dimension (LVDd) by echocardiography and LVEF by radionuclide angiography, and the plasma concentration of brain natriuretic peptides (BNP) and procollagen type III amino-terminal peptide (PIIIP), and thereafter these measurements were repeated at least every 6 to 12 months. Furthermore, the plasma level of matrix metalloproteinase(MMP)-9 was also measured at the entry and 6 months later.
Results: There were no significant differences in age, gender, NYHA class, LVDd, or LVEF at the entry between patients with (n=11) and without NIC (control: n=11). After the follow-up period of 31±11 months, LVDd significantly decreased and LVEF also significantly increased in NIC group (from 62.2±6.0mm and 33.4±7.2% to 60.3±6.7mm and 36.4±8.7%, respectively, p<0.05 for both), while LVDd significantly increased (from 61.2±4.6 to 64.5±6.6mm, p<0.05) with no significant change in LVEF in control group. BNP significantly decreased in NIC group (from 134.2±80.4 to 108.8±28.8pg/ml, p<0.05), while BNP significantly increased in control group (from 86.3±42.1 to 177.3±128.4pg/ml, p<0.05). Although there was a decrease tendency in MMP-9 level in NIC group (43±21 to 32±9ng/ml, p=0.09), PIIIP level significantly decreased in NIC group (from 0.61±0.16 to 0.51±0.13 U/ml, p<0.05) but not in control group,
Conclusion: Long-term nicorandil therapy might reverse left ventricular remodeling in patients with mild to moderate CHF.