Suppression of platelet COX-1 activity by aspirin is much more
variable in patients with heart disease than in healthy individuals,
Italian researchers report in the August issue of Clinical
Pharmacology and Therapeutics.

"Complete and persistent suppression of platelet thromboxane A2
biosynthesis by aspirin is mandatory to fulfill its
cardioprotection," Dr. Maria G. Sciulli of the Catholic University
School of Medicine in Rome and colleagues note in their article.
Several lines of evidence indicate that COX-1 is the cyclooxygenase
isoform involved in TXA2 generation.

The researchers investigated the ability of aspirin to inhibit
platelet COX-1 by measuring thromboxane B2 (TXB2) levels. The study
involved 30 patients with coronary heart disease (CHD) and ten
healthy subjects. Both patients and controls were on long-term
aspirin therapy, 100 mg daily.

The researchers administered one dose of aspirin, 160 mg, at
baseline and measured serum TXB2 levels 12 hours later.

CHD patients had a much wider range of TXB2 levels than healthy
subjects.

The controls had a range of TXB2 of 0.6 to 7.9 ng/mL, with a median
of 2.1 ng/mL and a standard deviation (SD) of 3.2 ng/mL.

In CHD patients, the TXB2 range was 0.15 to 47.0 ng/mL, with a mean
of 8.5 ng/ml. Eight patients, or 27%, had TXB2 levels more than two
SD above the mean TXB2 level of healthy controls.

A TXB2 level of 8.4 ng/mL was determined to be the limit for
adequate inhibition of COX-1 by aspirin.

High TXB2 generation was not dependent on COX-2 activity,
leukocytes, or cigarette smoking, "but was plausibly a result of
defective suppression of platelet COX-1 activity," the investigators
believe.

"The measurement of the serum TXB2 level seems to be an appropriate
biomarker to identify patients who have an inadequate inhibition of
platelet COX-1 activity by aspirin," Dr. Sciulli and colleagues
conclude.

Clin Pharmacol Ther 2006;80:115-125