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

Aims A new formulation, low dose microencapsulated aspirin, permits slow ab sorption 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 wa s as effective as enteric coated (EC) aspirin as an inhibitor of platelet f unction 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 a nd collagen induced platelet aggregation and release of 5-hydroxytryptamine (EC50 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 vitr o to determine the EC50 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 EC50 s on day 28 showed small but significant increases fr om baseline (day 0) in aggregation in patients randomised to microencapsula ted aspirin 162.5 mg (0.62-0.85, P=0.0482) and in both aggregation and rele ase in patients randomised to aspirin EC 150 mg (0.95-1.20, P=0.0002, 8.4-1 1.7, P<0.0001, respectively) signifying enhanced antiplatelet activity. No changes were seen in patients continuing on aspirin EC 75 mg. Results follo wing addition of high dose aspirin in vitro suggest that mechanisms other t han thromboxane synthesis may be operative in the long term effects of micr oencapsulated 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 a nd subsequent platelet activity by all preparations of aspirin, although bo th microencapsulated aspirin 162.5 mg and aspirin EC 150 mg are slightly mo re effective than aspirin EC 75 mg. A randomised trial is now required to d etermine whether microencapsulated aspirin is associated with fewer gastric side-effects.