EFFICACY AND SAFETY OF EXTENDED-RELEASE ISOSORBIDE-MONONITRATE FOR STABLE EFFORT ANGINA-PECTORIS

The efficacy and safety of extended-release isosorbide mononitrate tab lets were evaluated in patients with stable effort angina. In a double -blind study, 313 patients with stable effort-induced angina were rand omized to receive placebo or extended-release isosorbide mononitrate: 30, 60, 120 or 240 mg once daily in the morning. Serial exercise testi ng was performed using the standard Bruce treadmill protocol on days 1 , 7, 14, 28 and 42 immediately before morning drug administration and 4 and 12 hours after administration. After initial dosing, all groups that received extended-release isosorbide mononitrate had significant (p < 0.01) increases in mean total exercise time of approximately 30 t o 50 seconds in relation to placebo 4 and 12 hours after administratio n. On day 42, mean changes from baseline in total exercise time of pat ients who received 120 or 240 mg of extended-release isosorbide mononi trate exceeded placebo by approximately 50 to 60 seconds 4 hours after dosing (p < 0.01), and by 30 to 35 seconds 12 hours after dosing (p l ess-than-or-equal-to 0.05). No significant difference was detected bet ween responses to extended-release isosorbide mononitrate and placebo 24 hours after administration (i.e., immediately before the next dose) . Thus, there was neither significant activity nor demonstrable reboun d of effort-induced angina (zero-hour effect) at the end of the dosing interval. Transient headache was the most prevalent adverse experienc e. Extended-release isosorbide mononitrate (120 and 240 mg administere d orally once daily) significantly prolonged exercise time to developm ent of moderate effort-induced angina 4 and 12 hours after dosing duri ng long-term therapy, without development of nitrate tolerance. The dr ug was well tolerated, and no zero-hour rebound of effort-induced angi na was observed.