The antianginal effects of diltiazem 180 mg/day and propranolol 240 mg/day, alone and in combination, were investigated in 15 patients with effort related angina in a double blind placebo controlled crossover trial, with each period of treatment lasting four weeks. Patients performed a symptom limited treadmill exercise test at the end of each period of treatment. Mean (SEM) time to onset of angina was increased from 293(32) s when receiving placebo to 347(38) s when receiving diltiazem alone, to 350(30) s when receiving propranolol alone, and further to 421(34) s when receiving diltiazem and propranolol combined. Similar changes occurred in the duration of exercise testing and time to 1 mm ST segment depression. The sum of ST segment depression at peak exercise was reduced by both diltiazem and propranolol alone compared with placebo, and combination treatment produced a further significant improvement. Rate pressure product was significantly reduced at rest and at peak exercise after propranolol alone and combination treatment. The study clearly showed the superior value of diltiazem and propranolol combined in effort related angina when compared with either drug used alone.

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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.