INFLUENCE OF LOW-DOSE INTRAVENOUS NITRATE THERAPY ON THE ANTICOAGULATORY EFFECT OF HEPARIN

Background and Aim: Controversial studies concerning the fact that sim ultaneous 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 compar ison to placebo on the anticoagulatory effect of a constant heparin in fusion in patients with CAD. Patients and Methods: 22 stable and mobil e inpatients (two female, 20 male; aged 47 to 80; documented CAD in 20 patients, one patient with atrial fibrillation, one patient with susp ected CAD), kept on a therapeutic heparin infusion for several days (p rolongation of the partial thromboplastin time [PTT] by 1.5 to two-fol d), were included. Study course: Day 1: Discontinuation of nitrate med ication, optimization of heparin therapy and fixation of the heparin d ose (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% N aCl solution as placebo (3 ml/h) with heparin over 24 hours. Day 3: Su bstitution of NaCl solution by randomised single-blind intravenous adm inistration 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. Result: As compared to p lacebo, 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.; Man n-Whitney test). After GTN or ISDN had been discontinued, no change in PTT values was seen during the following five hours. Conclusion: Ther e is no indication of a pharmacodynaniic relevant interaction between heparin and low-dose intravenous nitrate therapy in patients with CAD.