Effects of very low dose and enteric-coated acetylsalicylic acid on prostacyclin and thromboxane formation and on bleeding time in healthy subjects

Objective: Low dose acetylsalicylic acid (ASA) is widely used as an anti-ag gregatory agent in the primary and secondary prevention of cardiovascular d iseases. In an effort to spare prostacyclin formation and to reduce gastroi ntestinal side-effects, both very low doses and enteric-coated formulations of ASA have been introduced. However, it still remains unclear whether the se different formulations and dosages are equally effective with respect to inhibition of platelet aggregation and thromboxane A(2) (TXA(2)) formation . Methods: In a randomized study, we therefore investigated the effects of 10 0 mg ASA plain (p), 100 mg ASA enteric-coated (ec) and 40 mg ASA (p) to 36 healthy male subjects given for 7 days on platelet aggregation and endogeno us prostanoid formation rates. Platelet aggregation and platelet TXB2 relea se in platelet rich plasma (PRP) and serum TXB2 and 6-keto-PGF(1 alpha) lev els were determined at baseline and after 7 days of each medication. The ur inary metabolites of TXA(2) (2,3-dinor-TXB2) and prostacyclin (2,3-dinor-6- keto-PGF(1 alpha)) were measured by gas chromatography/tandem mass spectrom etry in 24-h-urines at baseline and on day 7 of each medication. Results: Collagen-induced platelet aggregation was 73.1 +/- 1.6% of maximal aggregation at baseline. It was inhibited by 68.9%, 58.6% and 24.0% by ASA 100 mg plain, 100 mg enteric-coated, and 40 mg plain on day 7, respectivel y. Platelet TXB2 release was 11 592.0 +/- 367.5 pg.ml(-1) PRP. It was inhib ited by 90.1%, 86.5%, and 55.2% by ASA 100 mg plain, 100 mg enteric-coated, and 40 mg plain, respectively. Serum TXB2 was almost completely reduced on day 7 by 100 mg ASA, but not by 40 mg ASA; serum 6-keto-PGF(1 alpha) was s lightly, but significantly reduced in all three groups. Urinary 2,3-dinor-T XB2 excretion was 196.0 +/- 41.5 pg.mg(-1) creatinine at baseline. It was r educed by 80.3% and 79.1% by ASA 100 mg plain and enteric-coated, respectiv ely (each P < 0.05 Versus baseline), but only by 55.4% by ASA 40 mg plain ( P < 0.05 versus both formulations of ASA 100 mg). Conclusions: Our present data show that the plain and enteric-coated formul ations of 100 mg ASA are equally effective in inhibiting platelet aggregati on, platelet thromboxane production, and urinary 2,3-dinor-TXB2 excretion r ates. In contrast, a very low dose of 40 mg ASA was significantly less effe ctive in inhibiting these indices of platelet activation in healthy human s ubjects. ASA enteric-coated 100 mg may be a useful alternative to 100 mg AS A (p) in patients with gastrointestinal side-effects, whereas 40 mg ASA (p) may be too low to inhibit sufficiently platelet activity in patients with cardiovascular diseases in whom platelet activity is increased.