Comparison of antiplatelet activity of microencapsulated aspirin 162.5 mg (Caspac XL), with enteric coated aspirin 75 mg and 150 mg in patients with atherosclerosis

Abstract

Aims A new formulation, low dose microencapsulated aspirin, permits slow absorption of aspirin and presystemic acetylation of platelet cyclo-oxygenase within the portal circulation, potentially avoiding deleterious effects on gastric and systemic prostaglandin synthesis. The objective of this study was to determine whether the administration of microencapsulated aspirin was as effective as enteric coated (EC) aspirin as an inhibitor of platelet function in patients with atherosclerosis. Methods One hundred and four patients were enrolled and randomised after a run in period of at least 14 days on aspirin EC 75 mg (day 0), to receive either microencapsulated aspirin 162.5 mg (n=34), aspirin EC 150 mg (n=36) or continue on aspirin EC 75 mg (n=34) for 28 days. Serum thromboxane B 2 and collageninduced platelet aggregation and release of 5-hydroxytryptamine (EC 50 values) were measured on days 0 and 28. Aggregation/release EC 50 s were then repeated in the presence of a large dose of aspirin added in vitro to determine the EC 50 at the maximum level of platelet inhibition. Results Median thromboxane B 2 levels were low after 14 days run-in therapy with aspirin EC 75 mg, but significant further reductions were seen on day 28 in patients randomised to microencapsulated aspirin 162.5 mg ( P=0.0368) and aspirin EC 150 mg ( P=0.0004) compared with those remaining on aspirin EC 75 mg. Median EC 50 s on day 28 showed small but significant increases from baseline (day 0) in aggregation in patients randomised to microencapsulated aspirin 162.5 mg (0.62-0.85, P=0.0482) and in both aggregation and release in patients randomised to aspirin EC 150 mg (0.95-1.20, P=0.0002, 8.4-11.7, P<0.0001, respectively) signifying enhanced antiplatelet activity. No changes were seen in patients continuing on aspirin EC 75 mg. Results following addition of high dose aspirin in vitro suggest that mechanisms other than thromboxane synthesis may be operative in the long term effects of microencapsulated aspirin 162.5 mg and aspirin EC 150 mg over aspirin EC 75 mg. Conclusions The results show good inhibition of thromboxane B 2 synthesis and subsequent platelet activity by all preparations of aspirin, although both microencapsulated aspirin 162.5 mg and aspirin EC 150 mg are slightly more effective than aspirin EC 75 mg. A randomised trial is now required to determine whether microencapsulated aspirin is associated with fewer gastric side-effects.

Differences in the effects of extended‐release aspirin and plain‐formulated aspirin on prostanoids and nitric oxide in healthy volunteers

“…The present results suggest that the better platelet function profile of ER formulations of ASA in comparison with PF may be influenced by the role of SA and the relative lack of interference with prostacyclin synthesis. Moreover, our findings support the hypothesis put forward by Brown et al [25] that the anti‐aggregant effect of microencapsulated ASA is not entirely dependent on the inhibition of platelet thromboxane synthesis.…”

“…A study by Brown et al [25] showed that the inhibition of platelet aggregation after the administration of a microencapsulated form of ASA (Caspac XL) was not entirely dependent on the inhibition of platelet thromboxane synthesis. This finding showed that an additional mechanism may be involved in the differences in pharmacokinetic profile between ER and PF ASA.…”