Trial of repeated low-dose aspirin in diabetic angiopathy

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.

The Effects of Different Aspirin Dosing Frequencies and the Timing of Aspirin Intake in Primary and Secondary Prevention of Cardiovascular Disease: A Systematic Review

“…A distinction has been made between studies comparing the same or a different overall daily dose. For comparisons of the same overall dose, most results across five studies 36,37,39,40,42 did not show statistically significant differences in platelet function; two studies 15,39 found a significant difference (favoring twice-daily dosing) with one but not the other of two PFTs used, respectively. There is thus little evidence to suggest a potential benefit from twice-daily dosing in these populations (Type 2 diabetes mellitus (T2DM) with or without CAD/CVD, or ischemic heart/cerebrovascular disease (IHD/ ICD)).…”

“…32 Once-vs. twice-daily (or more) administration. The 11 studies 15,[35][36][37][38][39][40][41][42][43]45 (see Table 1) comparing a different frequency of daily dosing were heterogeneous in terms of study design, duration of treatment, and population (diabetes, CAD, CVD, ET); all were short-term studies with up to 2 months per treatment period reporting as their main outcome PFT results, mainly light transmission aggregometry (LTA), serum thromboxane levels, and VerifyNow Aspirin. Where possible, these results have been presented in forest plots (see Figures 3, 4), with the remaining results tabulated (see Supplementary File Tables 3-7).…”

Managing the diabetic patient with acute myocardial infarction

“…20,35 Other major thrombolytic studies, and other investigations of aspirin use in at risk patients with diabetes, show similar benefit to that in non-diabetic subjects (Figure 2), 36,37 even though some reports suggest that diabetic patients need a higher dose of aspirin than do patients without diabetes. 38 It would appear logical to initiate aspirin treatment with thrombolytic therapy in diabetic patients, and continue in a dose of 300 mg daily of enteric coated aspirin long term. 37…”

Clinical Trials of Antiplatelet Agents in Diabetes Mellitus: Rationale and Results

“…Second, platelet turnover may be accelerated in diabetic patients. 25 Thus, new platelets without cyclooxygenase blockade may enter the circulation as blood aspirin levels fall, if short-acting preparations are used. Furthermore, a very low blood level of aspirin is all that is needed to block cyclooxygenase and, hopefully, to encourage endothelial release of prostacyclin.…”