[Plasma volume expansion may explain the attenuation of antianginal activity of oral isosorbide dinitrate in long-term therapy].
The aim of the study was to evaluate whether tolerance to oral isosorbide dinitrate in sustained-release form (ISDN-SR) may be related to reduction in hematocrit (HCT)--an indirect indicator of plasma volume expansion.


METHODS
In a double blind, cross-over and placebo (P) controlled study 38 men, with mean age 52.5 +/- 7.4 years, with stable angina and angiographically proven coronary artery disease, received ISDN-SR 120 mg or P as initial dose and after 7 days of therapy: 4-times-daily (ISDN-SR 480 mg a day) and once-daily (ISDN-SR 120 mg a day). Venous HCT was measured: before treatment and after each of the 3 long-term phases. Antianginal efficacy of ISDN-SR 120 mg was evaluated by analysis of walking time to ischemia (WTI) on treadmill during stress tests performed 2 and 6 hours after drug ingestion in acute and long-term therapy.


RESULTS
6 hours after first ingestion of ISDN-SR 120 mg the mean walking time to ischaemia WTI was significantly improved in comparison to P by 58.4% (p < 0.0001) and after 7 days of once-daily treatment by 36.2% (p < 0.01) but not after the 4-times-daily period (NS). HCT fell from mean 43.2 +/- 3.6% before and 42.0 +/- 3.4% (NS) after P phase, to 40.5 +/- 3.0% (p < 0.05) after 4-times-daily period, but HCT remained unchanged after one week of once-daily treatment (NS).


CONCLUSIONS
Significant reduction in hematocrit--an indirect indicator of plasma volume expansion--during oral ISDN-SR 120 mg in long-term therapy 4-times-daily, when tolerance occurred, but not once-daily (without tolerance), may contribute to the mechanism of attenuation of antianginal activity of nitrates.
Kośmicki
M
M
Klinika Choroby Wieńcowej, Instytutu Kardiologii w Warszawie.
Sadowski
Z
Z
D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000494:pharmacology* / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology* / Q000627:therapeutic use*; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D010953:Plasma Volume / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use*
D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate