A Comparison of Nicorandil With Isosorbide Mononitrate in Elderly Patients With Stable Coronary Heart Disease: The SNAPE Study

Abstract

Background: Nicorandil, a potassium channel opener, is an effective antianginal drug, but its therapeutic evaluation is still limited.
Objective: The efficacy and safety of nicorandil compared with isosorbide mononitrate (ISMN) was evaluated in the treatment of elderly patients (>=65 years) with stable angina pectoris and a positive exercise test result (>=0.1 mV ST-segment depression).
Methods and Results: In a multicenter, double-blind, double-dummy, controlled trial, 194 patients were randomly assigned to 10 mg nicorandil twice daily or 20 mg ISMN twice daily. For the evaluation of ischemic variables, a symptom-limited bicycle exercise test was performed after 1 week of placebo treatment and after 4 weeks of nicorandil or ISMN treatment. Clinical assessment for safety and side effects occurred at 2-week intervals. One hundred seventy-eight patients were analyzed on an intent-to-treat basis and 145 were terminated from the study per protocol (efficacy analysis). During treatment, within both treatment groups exercise testing revealed a significant postponement of the onset of ischemia (nicorandil, P < .01; ISMN, P = .03) and angina (P =< .03 for both) and a decrease of maximum ST depression (ISMN, P < .002) compared with baseline. There were no differences between the groups for both intent-to-treat and efficacy analysis, with the exception of the rate-pressure product, which was increased (P = .03) in the nicorandil group. Safety and well-being variables were not different between groups, but the frequency of angina decreased (P = .02) in the ISMN group.
Conclusions: These data suggest that, although nicorandil seems to be as safe and effective as ISMN for the treatment of stable angina in elderly patients, ISMN may be superior to nicorandil for the symptomatic treatment of daily angina in this patient population.

Introduction

Nicorandil, a nicotinamide derivative with a nitrate moiety, combines the smooth muscle-relaxing property of both nitrates and nicotinamide with its ability to increase potassium ion conductance.^[1] As a result, nicorandil has a direct (preload and afterload) vasodilating effect on normal and diseased coronary arteries and peripheral vessels.^[1,2] These characteristics have justified its assessment as an antianginal compound in numerous experimental and clinical studies.^[1] Although nicorandil has been shown to be efficacious and safe in patients with stable angina pectoris compared with placebo^[3-5] as well as with other antianginal agents,^[6-12] its therapeutic evaluation is still limited. This international, multicenter, randomized, double-blind, double-dummy study (S) was designed to assess the efficacy and safety of nicorandil (N) compared with isosorbide mononitrate for the treatment of angina pectoris (AP) in elderly (E) patients with stable coronary heart disease (SNAPE).