Objective: We assessed the production of eicosanoids and the effects of very low dose aspirin in patients with stable angina under basal conditions and during rapid atrial pacing.
Background: Platelet activation occurs in acute ischemic syndromes but is still controversial in stable angina. Very low dose aspirin is known to be platelet selective and can be used to test the hypothesis of the platelet origin of increased thromboxane production in stable angina.
Methods: Urinary excretion of eicosanoids was measured in 42 patients, including 24 patients with and 18 patients without coronary artery disease. The effects of 50 mg/day of aspirin were measured at rest and during pacing-induced ischemia in 10 patients with stable angina and were compared with a similar group of patients not treated by aspirin.
Results: Excretion of 11-dehydro-thromboxane B2 was 2.6 times higher in patients with stable angina than in healthy subjects (mean [+/- SEM] 74.8 +/- 13.0 [24 patients] vs. 29.0 +/- 5.4 [18 patients] ng/mmol of creatinine, p < 0.01). Urinary prostacyclin metabolite levels did not differ between the two groups. Treatment for 8 days with 50 mg/day of aspirin inhibited platelet cyclooxygenase, as reflected by the 97% reduction of in vitro serum thromboxane production. This aspirin regimen normalized the level of urinary thromboxane metabolites in patients with angina (17.3 +/- 3.4 ng/mmol of creatinine [10 patients], p < 0.001 from baseline level before treatment) and did not change prostacyclin metabolite levels. Atrial pacing in patients with angina not treated with aspirin caused lactate and thromboxane release into the coronary sinus. In patients with very low dose aspirin therapy, pacing did not cause thromboxane release despite inducing myocardial ischemia. However, fractional lactate extraction decreased less sharply in patients with than without aspirin therapy.
Conclusions: Thromboxane production is greatly increased in patients with stable angina. Very low dose aspirin administered to these patients reduces thromboxane synthesis to normal levels, preserves prostacyclin biosynthesis and prevents acute thromboxane release into the coronary circulation during pacing-induced ischemia. Our data suggest that platelets (not monocytes/macrophages) are activated in stable angina to produce thromboxane.