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 B2 and collagen-induced platelet aggregation and release of 5-hydroxytryptamine (EC50 values) were measured on days 0 and 28. Aggregation/release EC50s were then repeated in the presence of a large dose of aspirin added in vitro to determine the EC50 at the maximum level of platelet inhibition. RESULTS:Median thromboxane B2 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 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 B2 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.
RCT Entities:
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 B2 and collagen-induced platelet aggregation and release of 5-hydroxytryptamine (EC50 values) were measured on days 0 and 28. Aggregation/release EC50s were then repeated in the presence of a large dose of aspirin added in vitro to determine the EC50 at the maximum level of platelet inhibition. RESULTS: Median thromboxane B2 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 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 B2 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.
Authors: W N Charman; S A Charman; D C Monkhouse; S E Frisbee; E A Lockhart; S Weisman; G A Fitzgerald Journal: Br J Clin Pharmacol Date: 1993-11 Impact factor: 4.335
Authors: Paul A Gurbel; Kevin P Bliden; Junhong Zhu; Emanuel Troullos; Robert Centofanti; Sistine Jarvis; Palak Venkataraman; Udaya S Tantry Journal: J Thromb Thrombolysis Date: 2018-01 Impact factor: 2.300