Effects of combination therapy with low-dose aspirin and warfarin on platelet functions after heart valve replacement.
To evaluate the efficacy and safety of combination therapy with aspirin and warfarin for preventing the development of thromboembolism, we compared the effects of low-dose aspirin (81 mg/day) on platelet functions to those of ticlopidine (300 mg/day) in heart valve replacement patients. Experiments were performed in two groups; the first group within 1 month after operation (the unstable period) and the second group between 3 months and 3 years after operation (the stable period). At the stable period, low-dose aspirin inhibited platelet aggregation induced by ADP, collagen, or arachidonic acid, and suppressed the increase in intracellular Ca2+ concentration [( Ca2+]i) induced by thrombin significantly. On the other hand, ticlopidine inhibited platelet aggregation induced by ADP or collagen, but did not suppress arachidonic acid-induced aggregation and the thrombin-induced [Ca2+]i increase. At the unstable period, the combination therapy of low-dose aspirin plus warfarin did not prolong the bleeding time compared to ticlopidine plus warfarin. And low-dose aspirin inhibited platelet aggregation induced by ADP, collagen or epinephrine, and especially blocked arachidonic acid-induced aggregation. Ticlopidine inhibited ADP-, collagen- or U-46619-induced aggregation, but did not affect on the increase in [Ca2+]i induced by thrombin. From the results in this study, we suggest that the combination therapy with low-dose aspirin (81 mg/day) and warfarin is safe as an antithrombotic medication in heart valve replacement, and results in the inhibition of platelet functions without any side effect calling for special mention at the early unstable period after operation.
Kobune
K
K
Department of Pharmacology, Tokyo College of Pharmacy, Japan.
Inoue
M
M
Morikawa
M
M
Tsuboi
M
M
Takanami
Y
Y
Iwane
Y
Y
Kudo
T
T
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D006350:Heart Valve Prosthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010976:Platelet Count; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013923:Thromboembolism / Q000517:prevention & control*; D013988:Ticlopidine / Q000494:pharmacology; D014859:Warfarin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D016718:Arachidonic Acid; D014859:Warfarin; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D013988:Ticlopidine; D001241:Aspirin; D002118:Calcium