NICORANDIL SAFETY IN THE LONG-TERM TREATMENT OF CORONARY HEART-DISEASE

The results of an open prospective study that evaluated the long-term clinical safety of nicorandil are presented. This study included 199 patients with severe chronic stable angina treated over a 1-year period. The most often reported adverse event was headache, which was responsible for most of the study withdrawals due to clinical intolerance (9.6%). When using a progressive titration scheme, this incidence was substantially reduced to 2.7%. As with other less frequent adverse events (dizziness, gastrointestinal disorders), headaches were reported as being mild to moderate in severity, were experienced during the first days of treatment, and, if treatment was maintained, usually resolved within a few days. The incidence of adverse events was not modified when nicorandil was given in combination with a betablocker, a calcium antagonist, or both agents. Cardiovascular safety was satisfactory and laboratory parameters were not altered. At the end of the study, 70% of patients were maintained on nicorandil. These results are in agreement with those reported from the nicorandil safety database, which gathered 1152 patients treated by nicorandil, including those of the present study. In comparative studies of nicorandil versus beta-blockers, calcium antagonists, or nitrates, the overall incidence of adverse events was no different between the two treatment groups, although the safety profile differed according to the drug category. During the course of several clinical studies, nicorandil was associated with antihypertensive, antidiabetic, hypolipemic, or other antianginal agents; these combinations did not increase the incidence of adverse events or study withdrawals. In all long-term clinical studies using doses up to 80 mg/day, nicorandil has had a favorable cardiovascular safety profile. There were no meaningful changes in heart rate and blood pressure, and ECG at rest and during exercise did not show rhythm or conduction disorders or QT- and ST-segment modification. Up to now, there has been no evidence that nicorandil exerts a negative inotropic effect. The nicorandil safety profile was not different in patients aged over 65 years (33%). Finally, nicorandil did not affect the usual laboratory parameters, including blood potassium and glucose levels, and the blood lipid profile. Therefore, nicorandil, alone or in combination, appears to be a safe, active antianginal agent for the long-term treatment of a wide range of patients with chronic stable angina.