The role of extraplatelet thromboxane A2 in unstable angina investigated with a dual thromboxane A2 inhibitor: importance of activated monocytes

Coron Artery Dis. 1994 Feb;5(2):137-45. doi: 10.1097/00019501-199402000-00007.


Background: The role of thromboxane A2 (TxA2) in unstable angina has not yet been defined. TxA2 receptor antagonists may be of value in studying this role.

Methods: To investigate whether TxA2 has a pathogenetic effect on the occurrence of myocardial ischemia and from what source TxA2 originates, we studied TxA2 formation by unstimulated monocytes from patients with unstable angina (n = 40), stable effort angina (n = 20), and controls (n = 20). We also compared the effects of picotamide (1200 mg/day), a TxA2-synthase inhibitor and TxA2-receptor antagonist, with those of aspirin (325 mg/day) on myocardial ischemia and TxA2 formation by monocytes and platelets. The double-blind randomized study was performed on patients with unstable angina on continuous Holter monitoring.

Results: In the presence of autologous lymphocytes, unstimulated monocytes from patients with unstable angina formed significantly (P < 0.001) more TxA2 than those from controls or from patients with effort angina. Although TxA2 formation by circulating monocytes and platelets was inhibited to a greater degree by aspirin than by picotamide (88 +/- 6 and 98 +/- 2%, respectively, versus 65 +/- 2 and 74 +/- 1%, P < 0.001), aspirin failed to affect the occurrence of myocardial ischemia whereas picotamide significantly (P < 0.001) reduced the number of anginal attacks (84.8%), silent ischemic episodes (64.2%), and overall duration of ischemia (69.8%), in comparison to the run-in period.

Conclusions: These results indicate that TxA2 formed by monocytes contributes to the pathogenesis of myocardial ischemia in unstable angina. TxA2 formation occurs mainly in extravascular spaces, probably within the coronary vascular wall. Picotamide appears to control myocardial ischemia effectively in patients with unstable angina.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angina Pectoris / pathology
  • Angina Pectoris / physiopathology
  • Angina, Unstable / drug therapy*
  • Angina, Unstable / pathology
  • Angina, Unstable / physiopathology*
  • Aspirin / pharmacology
  • Aspirin / therapeutic use
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / physiology*
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / physiopathology*
  • Myocardial Ischemia / prevention & control*
  • Phthalic Acids / pharmacology
  • Phthalic Acids / therapeutic use*
  • Placebos
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prospective Studies
  • Thromboxane A2 / antagonists & inhibitors
  • Thromboxane A2 / biosynthesis
  • Thromboxane A2 / physiology*


  • Phthalic Acids
  • Placebos
  • Platelet Aggregation Inhibitors
  • Thromboxane A2
  • picotamide
  • Aspirin