1986 Volume 50 Issue 2 Pages 181-187
We examined platelet aggregation and plasma levels of thromboxane B2, a stable metabolite of thromboxane A2, in patients with unstable angina and correlated these platelet indices with the response to antianginal conventional therapy such as isosorbide dinitrate and calcium channel blocker. Eight of 36 patients exhibited anginal attacks more than 5 times/week in spite of the therapy, designated refractory unstable angina, associated with augmented platelet aggregation induced by arachidonate (0.3 mM, 71 ± 3%, mean ± SEM) and collagen (2 μg/ml, 72 ± 5%), and elevated plasma levels of thromboxane B2 (350 ± 19 pg/ml). In the remainder of the patients whose anginal attacks were effectively subsided by the therapy, platelet aggregation was much lower (arachidonate: 34 ± 9%, collagen: 31 ± 8%, p < 0.01) and plasma levels of thromboxane B2 were also lower (295 ± 12 pg/ml, p < 0.05). To evaluate the effect of selective thromboxane A2 blockade on clinical findings and platelet reactivity in refractory unstable angina, OKY-046 (600 mg/day, p.o.) was administered to another 14 patients with refractory unstable angina in addition to the conventional therapy. We found that platelet aggregation induced by arachidonate (71 ± 4%) and collagen (65 ± 8%) was markedly reduced (44 ± 7% and 24 ± 3%, respectively, p < 0.01) and plasma levels of thromboxane B2 (358 ± 31 pg/ml) and thromboxane B2 production in serum (29 ± 5 ng/ml) were also significantly reduced after OKY-046 treatment (262 ± 21 pg/ml, p < 0.05, and 1.4 ± 0.2 ng/ml, p < 0.001). In accordance with these findings, frequency of anginal attacks (8.4 ± 1.1 times/week) was markedly decreased to less than one half (3.6 ± 1.1 times/week, p < 0.01). Under these conditions, during the first month of admission occurrence of myocardial infarction in refractory unstable angina treated with OKY-046 was effectively decreased (7%) compared with that in controls (50%, p < 0.05). These results suggest that augmented platelet reactivity and thromboxane A2 production by platelets play a key role in the pathogenesis of refractory unstable angina.
