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Trial of repeated low-dose aspirin in diabetic angiopathy
Insights
Standard aspirin doses are ineffective for diabetic patients with increased platelet turnover. Continuous low-dose aspirin may prevent thrombosis in these individuals.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Diabetology
Background:
- Diabetic angiopathy is associated with increased platelet activation and turnover.
- Aspirin is commonly used to prevent cardiovascular events by inhibiting platelet aggregation.
Purpose of the Study:
- To compare the efficacy of aspirin in suppressing platelet aggregation and thromboxane synthesis in normal subjects versus patients with diabetic angiopathy.
- To evaluate the effectiveness of different aspirin dosing regimens in these populations.
Main Methods:
- Ten normal subjects and ten patients with diabetic angiopathy were studied.
- Aspirin doses ranged from 100 to 1,000 mg daily for one month, with intermittent 25 or 100 mg doses every six hours.
- Platelet aggregation and thromboxane synthesis were measured ex vivo.
Main Results:
- Intermittent aspirin dosing allowed for platelet aggregation and thromboxane synthesis in both groups.
- Diabetic patients showed similar gaps in suppression compared to normals, even with more frequent dosing.
- Standard aspirin regimens were insufficient to continuously inhibit platelet activity in diabetic angiopathy patients due to high platelet turnover.
Conclusions:
- Dose schedules of aspirin effective in normal individuals are insufficient for patients with diabetic angiopathy.
- The high rate of new platelet entry in diabetics necessitates continuous platelet suppression.
- Slow-release aspirin preparations are suggested for sustained inhibition of platelet thromboxane synthesis and aggregation to prevent thrombosis.
Abstract:
We compared the ability of aspirin to suppress platelet aggregation and thromboxane synthesis in ten normal subjects and ten patients with diabetic angiopathy and high rate of entry of new platelets into the circulation. When single doses of 100 to 1,000 mg aspirin were ingested daily for 1 month, there were time gaps between doses in which platelets from diabetics and normals aggregated and formed thromboxane ex vivo in response to the combination of arachidonic acid plus collagen. Similar gaps were also found for diabetics, but not for normals, following four daily doses (every six hours) of 25 or 100 mg. Our data show that dose schedules of aspirin which may suffice in normals are not effective in patients with diabetic angiopathy, presumably because these patients have a high rate of entry of new platelets into the circulation. We suggest that continual suppression of platelet thromboxane synthesis and aggregation by low-dose, "slow-release" preparations of aspirin would be an ideal long-term approach for the prevention of thrombosis in patients with a high rate of entry of new platelets into the circulation.