Persistent inhibition of platelet function during long-term treatment with 75 mg acetylsalicylic acid daily in men with unstable coronary artery disease.

Abstract

One-hundred-and-ninety-three men with unstable coronary artery disease (CAD) (i.e. unstable angina or a non-Q wave myocardial infarction) were randomized in a double-blind fashion to acetylsalicylic acid (ASA) 75 mg daily (n = 100) or placebo (n = 93) within 72 h of admission to the Coronary Care Unit. Platelet function was evaluated as ex vivo aggregation toward collagen and ADP before and after 5 days, 1, 12, 18 and 24 months of treatment. ASA decreased aggregation by collagen 1 mg l-1 from 81.3 +/- 1.7% before to 34.0 +/- 1.7% after 1 month (P less than 0.001), while no change was observed in the placebo group. Aggregation by ADP 1 microM after 1 month was 42.1 +/- 1.1% and 51.0 +/- 2.0% in the ASA and placebo groups respectively (P less than 0.001). The platelet inhibition by ASA was maintained during 24 months. All ASA patients had reduced aggregation during treatment. A cumulative dose of 300 mg (4 doses of 75 mg) was not enough for maximal inhibition at the second aggregation test. Thus, ASA 75 mg daily causes platelet inhibition in all patients without attenuation during long-term treatment. If low dose ASA is started in unstable coronary artery disease a loading dose exceeding 300 mg is suggested.