ISOSORBIDE DINITRATE IN THE TREATMENT OF CORONARY-ARTERY DISEASE

The improvement of our understanding of the pharmacology of nitrate derivatives has allowed rationalisation of their use in the treatment of coronary artery disease. The comprehension of the evolution of the sensitivity of the vessel wall to nitrate vasodilatation with time has enabled definition of a rhythm of administration which preserves therapeutic efficacy : a daily therapeutic window of 8 to 10 hours. The introduction of new galenic forms (slow release oral preparations and transdermal patches) facilitates the practical application of the << optimal >> pharmacokinetic profile. A single daily dose of slow release ISDN is effective in controlled trials versus placebo in the treatment of chronic stable angina. Many clinical trials have also shown the synergy of the anti-anginal effects of ISDN and betablockers, both in single dose studies and during prolonged administration. These therapeutic windows are not adapted to the treatment of acute coronary insufficiency (unstable angina, myocardial infarction) ; however, it has recently been shown that the use of small, fixed doses of intravenous ISDN over a 3 day period is usually adequate for controlling acute coronary insufficiency and is not associated with the phenomenon of tolerance.