[Effect of low-dosage intravenous nitrate therapy on the anticoagulant effect of heparin]

Controversial studies concerning the fact that simultaneous i.v. administration of heparin and glyceroltrinitrate (GTN) might reduce the anticoagulatory effect of heparin have been published. In a controlled and comparative study we therefore investigated the influence of the nitrates GTN or isosorbide dinitrate (ISDN) in comparison to placebo on the anticoagulatory effect of a constant heparin infusion in patients with CAD.

22 stable and mobile inpatients (two female, 20 male; aged 47 to 80; documented CAD in 20 patients, one patient with atrial fibrillation, one patient with suspected CAD), kept on a therapeutic heparin infusion for several days (prolongation of the partial thromboplastin time [PTT] by 1.5 to two-fold), were included. Study course: Day 1: Discontinuation of nitrate medication, optimization of heparin therapy and fixation of the heparin dose (mean dose 33,800 E/24 h in the GTN group and 32,700 E/24 h in the ISDN group). Day 2: Intravenous simultaneous administration of 0.9% NaCl solution as placebo (3 ml/h) with heparin over 24 hours. Day 3: Substitution of NaCl solution by randomised single-blind intravenous administration of GTN (n = 10; 0.1%, solved in NaCl; dose 2.8 +/- 0.5 mg/h) or ISDN (n = 12; 0.1%, solved in NaCl, dose: 4.8 +/- 0.8 mg/h) for 24 hours. Day 4: Discontinuation of nitrates.

As compared to placebo, the intravenous simultaneous administration of GTN or ISDN and heparin over 24 hours had no influence on the anticoagulatory effect of heparin when the areas under the curve of PTT values on days 2 and 3 were compared (PTT measurements at 8, 10 a.m., 1, 3, 6, 11 p.m.; Mann-Whitney test). After GTN or ISDN had been discontinued, no change in PTT values was seen during the following five hours.

There is no indication of a pharmacodynamic relevant interaction between heparin and low-dose intravenous nitrate therapy in patients with CAD.