Effect of aspirin dosage and enteric coating on platelet reactivity.
Although aspirin is effective in the prevention and treatment of cardiovascular diseases, the optimal dose remains uncertain. The purpose of this study was to compare the platelet inhibitory and prostacyclin-sparing effects of 2 doses (81 and 325 mg) and forms (enteric-coated and regular) of aspirin. Since platelet reactivity has been reported to increase after strenuous exercise, a known trigger of myocardial infarction, subjects were studied following maximal treadmill exercise as well as at rest. Forty male healthy subjects were evaluated using a randomized, double-blind, parallel study design. Blood samples were obtained before and after maximal treadmill exercise at baseline and after 7 days on aspirin therapy. Both enteric and regular aspirin in 81- and 325-mg dosages markedly inhibited adenosine diphosphate and epinephrine-induced aggregation at rest and after exercise. Aspirin also inhibited the platelet response to collagen as assessed by a longer lag time to aggregation. The prolongation of lag time was greater for 325 mg than for 81 mg (100 +/- 7 vs 91 +/- 7; p = 0.04, after exercise). There were no significant dose-related differences in plasma 6-keto-prostaglandin F1alpha level; however, enteric-coated aspirin inhibited the exercise-induced increase in 6-keto-prostaglandin F1alpha to a lesser extent than regular aspirin. Although both doses (81 and 325 mg) and types (regular and enteric-coated) of aspirin inhibited adenosine diphosphate and epinephrine-induced aggregation equally, the 325-mg dose inhibited collagen-induced aggregation to a greater extent than 81 mg. The greater platelet inhibition observed with 325 mg may be clinically relevant in acute coronary syndromes characterized by plaque rupture with extensive collagen exposure and platelet activation.
Feng
D
D
Institute for Prevention of Cardiovascular Disease, Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
McKenna
C
C
Murillo
J
J
Mittleman
M A
MA
Gebara
O C
OC
Lipinska
I
I
Muller
J E
JE
Tofler
G H
GH
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D013608:Tablets, Enteric-Coated
D013608:Tablets, Enteric-Coated; D015121:6-Ketoprostaglandin F1 alpha; D001241:Aspirin