[Isosorbide-5-mononitrate in angina pectoris: its efficacy and absence of tolerance and rebound with an eccentric type of administration].
214 patients with angina pectoris were randomized to placebo or isosorbide-5-mononitrate (ISMN) rapid release 5, 10 or 20 mg b.i.d. at 8 a.m. and 3 p.m. Exercise tests were performed between 8 a.m. and 10 p.m., before and 2 and 7 h after each dose on days 2 and 14 and before and 2 h after the morning dose on days 7 and 21. All doses of ISMN increased exercise duration significantly more than placebo, and this effect lasted throughout most of the day. It was maximal (73 s; 24%) 2 h after the morning dose, slightly attenuated but still significant at 7 h, increased 2 h after the second dose and attenuated but still greater than with placebo at 7 h. The increase was even greater at 3 weeks (99 s; 29%), perhaps due to a training effect. Similar improvement was observed in other exercise parameters. There was no significant dose response. There were 100% more anginal attacks in the placebo than in the 20-mg treatment group. No rebound (assessed by comparing exercise duration before the morning dose between the groups) was observed.


CONCLUSIONS
ISMN b.i.d. eccentrically has an antianginal effect throughout most of the day, peaking at 2 h. This effect is sustained during chronic therapy, without tolerance or rebound.
Schneeweiss
A
A
Cardiovascular Research Foundation, Bad Schwalbach, Germany.
Reisin
L
L
Marmor
A
A
Caspi
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000787:Angina Pectoris / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D002170:Canada; D004361:Drug Tolerance; D005080:Exercise Test / Q000187:drug effects / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007557:Israel; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013997:Time Factors; D006113:United Kingdom; D014481:United States; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate
Isosorbide-5-mononitrato nell'angina pectoris: efficacia ed assenza di tolleranza e rebound con una somministrazione di tipo eccentrico.