Plasma factor and platelet sensitivity to prostacyclin in patients with peripheral vascular disease before and after treatment with a combination of a cyclooxygenase and a phosphodiesterase inhibitor.
According to a pathogenetic concept originally presented by Moncada in 1977 a therapeutic combination of a low-dose cyclooxygenase inhibitor with a phosphodiesterase inhibitor might help in restoring a disturbed hemostatic balance, as thromboxane synthesis in the platelets should be inhibited to a greater extent than the prostacyclin synthesis of the endothelium. Therefore, we evaluated the influence of a therapeutic combination of cyclooxygenase inhibitors in different dosages (sulfinpyrazone, acetylsalicylic acid) with a phosphodiesterase inhibitor (dipyridamole) on platelet sensitivity and plasma factor in comparison to placebo treatment. We examined 76 males with peripheral vascular disease (PVD) stage IIa according to Fontaine in a double-blind randomized study over a 3 months period. Patients were divided into 4 groups and the different drugs were randomized as follows: I. 75 mg sulfinpyrazone and 75 mg dipyridamole, II. 150 mg ASA and 75 mg dipyridamole, III. 330 mg ASA and 75 mg dipyridamole, IV. placebo. Clinical symptoms as well as the plasma factor and the diminished platelet sensitivity to prostacyclin in patients with PVD remained unchanged throughout the whole observation period. Our findings suggest that no improvement in hemostatic dysregulation can be obtained by this combined treatment.
D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002986:Clinical Trials as Topic; D016861:Cyclooxygenase Inhibitors; D004176:Dipyridamole / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D013442:Sulfinpyrazone / Q000627:therapeutic use*; D014652:Vascular Diseases / Q000097:blood / Q000188:drug therapy*
D016861:Cyclooxygenase Inhibitors; D010726:Phosphodiesterase Inhibitors; D004176:Dipyridamole; D011464:Epoprostenol; D001241:Aspirin; D013442:Sulfinpyrazone