Long-term nicorandil therapy improves cardiac sympathetic nerve activity after reperfusion therapy in patients with first acute myocardial infarction

Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, reduces plasma norepinephrine concentration in patients with ischemic heart disease. However, long-term effects on cardiac sympathetic nerve activity (CSNA) as evaluated by I-123 -metaiodobenzylguanidine (MIBG) scintigraphy have not been determined for patients with acute myocardial infarction (AMI). Methods: We studied 40 patients with their first AMI who were treated with intravenous nicorandil before and after primary coronary angioplasty. After suspension of the initial intravenous nicorandil treatment, 20 patients were randomized to receive oral nicorandil (15 mg/d) (group A) and the other 20 patients received a placebo (group B). All patients were also treated with an angiotensin-converting enzyme (ACE) inhibitor or beta-blockers. The delayed heart-to-mediastinum count ratio (H/M ratio), delayed total defect score (TDS), and washout rate (WR) were determined from I-123-MIBG scintigraphy 3 wk and 6 mo after angioplasty. The left ventricular (LV) end-diastolic volume (EDV), LV end-systolic volume (ESV), and LV ejection fraction (EF) were determined by contrast left ventriculography, whereas plasma procollagen type III amino-terminal peptide (PIIINP) concentrations were also measured at the same time points. Results: Three weeks after angioplasty, TDS, H/M ratios, WR, LVEDV, LVESV, and LVEF were similar in both groups. After 6 mo, all of these parameters had improved in both groups. However, the extent of change in TDS was -9 +/- 6 in group A and -5 +/- 6 in group B (P < 0.05), whereas that in the H/M ratio was 0.15 +/- 0.13 and 0.07 +/- 0.11 (P < 0.05) and that in the WR was -12% +/- 8%and -5% +/- 11% (P < 0.05). The extent of change in LVEDV, LVESV, and LVEF in group A tended to exceed that in group B, but these changes were not statistically significant. We found significant correlations between the percent change in PIIINP and that of TDS from baseline to 6 mo in group A (r = 0.456, P < 0.05). Conclusion: Long-term nicorandil therapy can be more beneficial for CSNA and LV remodeling than short-term therapy in patients with AMI.