Augmented platelet reactivity and thromboxane A2 production possible aggravating factors in unstable angina.
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 micrograms/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 less than 0.01) and plasma levels of thromboxane B2 were also lower (295 +/- 12 pg/ml, p less than 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 less than 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 less than 0.05, and 1.4 +/- 0.2 ng/ml, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
D000787:Angina Pectoris / Q000097:blood*; D000789:Angina, Unstable / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000627:therapeutic use; D008297:Male; D008689:Methacrylates / Q000627:therapeutic use; D008875:Middle Aged; D010974:Platelet Aggregation; D013928:Thromboxane A2 / Q000097:blood*
D002121:Calcium Channel Blockers; D008689:Methacrylates; D013928:Thromboxane A2; D007548:Isosorbide Dinitrate; C034364:ozagrel