Reduction of daily life ischaemia by aspirin in patients with angina: underlying link between thromboxane A2 and macrophage colony stimulating factor.
OBJECTIVE
To evaluate whether aspirin reduces the incidence and frequency of daily life myocardial ischaemia in a cohort of patients with chronic stable coronary artery disease.


METHODS
Tertiary referral centre.


METHODS
60 patients with chronic stable coronary artery disease underwent 48 hour Holter monitoring to assess the incidence and frequency of daily life myocardial ischaemia. Those with myocardial ischaemia (40/60) entered a double blind, crossover trial of aspirin (300 mg/day for three weeks) versus placebo. After each treatment arm, 48 hour Holter monitoring was repeated and urinary thromboxane (Tx) B2, 11-dehydro-TxB2, plasma prothrombin fragment F1+2, macrophage colony stimulating factor (MCSF), and interleukin (IL)-6 were measured.


RESULTS
Aspirin reduced the total number and duration of ischaemic episodes from 339 to 251 and from 1765 to 1365 minutes, respectively (p < 0.01 for both). TxB2 was also reduced from 0.2 to 0.1 ng/mg creatinine, 11-dehydro-TxB2 from 3.3 to 1.3 ng/mg creatinine, F1+2 from 1.5 to 1.2 nmol/l, MCSF from 991 to 843 pg/ml, and IL-6 from 3.5 to 2.9 pg/ml (p < 0.05 for all). 11-dehydro-TxB2 excretion with and without aspirin was related to MCSF concentrations (p < 0.01), and the percentage reduction of MCSF by aspirin was related to the reduction of 11-dehydro-TxB2 (p < 0.05) and the reduction of the ischaemic burden compared with placebo (p < 0.05).


CONCLUSIONS
In patients with daily life ischaemia, aspirin reduces the incidence and frequency of ischaemic episodes as well as the systemic concentrations of haemostatic/inflammatory markers. Aspirin may prevent transient coronary flow reductions through platelet, thrombin, and cytokine inhibition.
Ikonomidis
I
I
University of Athens, Department of Clinical Therapeutics, Alexandra Hospital, Athens, Greece. ignoik@otenet.gr
Andreotti
F
F
Nihoyannopoulos
P
P
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000150:complications; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000652:urine; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000517:prevention & control* / Q000652:urine; D010446:Peptide Fragments / Q000032:analysis; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011516:Prothrombin / Q000032:analysis; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
D015415:Biomarkers; D015850:Interleukin-6; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C045879:prothrombin fragment 1.2; D013929:Thromboxane B2; D013928:Thromboxane A2; C049235:11-dehydro-thromboxane B2; D016173:Macrophage Colony-Stimulating Factor; D011516:Prothrombin; D001241:Aspirin