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Effects of combination therapy with low-dose aspirin and warfarin on platelet functions after heart valve replacement
K Kobune1, M Inoue, M Morikawa
1Department of Pharmacology, Tokyo College of Pharmacy, Japan.
Insights
Combination therapy with low-dose aspirin and warfarin is safe for preventing thromboembolism in heart valve replacement patients. This antithrombotic medication effectively inhibits platelet functions without significant side effects during the early post-operation period.
Area of Science:
- Cardiology
- Pharmacology
- Hematology
Background:
- Thromboembolism is a significant risk following heart valve replacement.
- Optimizing antithrombotic therapy is crucial for patient outcomes.
Purpose of the Study:
- To evaluate the efficacy and safety of low-dose aspirin (81 mg/day) combined with warfarin.
- To compare the antiplatelet effects of aspirin versus ticlopidine in heart valve replacement patients.
Main Methods:
- Patients were divided into two groups: unstable (within 1 month post-operation) and stable (3 months to 3 years post-operation).
- Platelet functions, including aggregation and intracellular calcium concentration, were measured.
- Bleeding times were assessed for combination therapies.
Main Results:
- In the stable period, low-dose aspirin significantly inhibited platelet aggregation and thrombin-induced calcium increase, while ticlopidine had a more limited effect.
- In the unstable period, aspirin-warfarin combination did not prolong bleeding time compared to ticlopidine-warfarin.
- Low-dose aspirin demonstrated potent inhibition of platelet aggregation, particularly arachidonic acid-induced aggregation.
Conclusions:
- Combination therapy with low-dose aspirin (81 mg/day) and warfarin is a safe antithrombotic strategy for heart valve replacement patients.
- This regimen effectively inhibits platelet functions during the early, unstable period after surgery without notable side effects.
Abstract:
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.