A randomized, controlled study on the influence of acetaminophen, diclofenac, or naproxen on aspirin-induced inhibition of platelet aggregation.

Nonsteroidal anti-inflammatory drugs (NSAID) may interfere with aspirin (acetylsalicylic acid) and increase the risk for cardiovascular events. The clinical relevance is uncertain. The aim of this study was to analyse the influence of a co-administration of aspirin and NSAID on platelet aggregation. In a randomized, placebo controlled trial, eleven healthy volunteers were studied during 4 separate study periods of 4 days each. Individuals were treated on each occasion with 100 mg aspirin daily in combination with either 3 x 1 g acetaminophen, 3 x 50 mg diclofenac, 3 x 250 mg naproxen, or 3 x 1 placebo. Primary hemostasis was assessed with a platelet function analyser (PFA-100), which measures the closure time (CT) of a collagen- and epinephrine-coated pore by aggregating platelets in flowing blood. Naproxen enhanced the anti-aggregatory action of aspirin after 24 h (CT rising from 104+/-16 s at baseline to 212+/-69 s at 24 h, P<0.001), which was not seen with any other drug combination. Diclofenac reduced the anti-aggregatory action of aspirin in the first two days, since the CT did not rise significantly (109+/-19 s, 148+/-56 s, and 168+/-66 s at 0 h, 24 h, 48 h, respectively, P>0.05). Acetaminophen had no effect compared with placebo. After 4 days of treatment platelet aggregation was similarly inhibited by all combinations. We conclude that a co-administration of NSAID and aspirin may interfere with platelet inhibition at the beginning of a treatment with an increase of naproxen and a decrease of diclofenac. This effect is lost after 4 days, suggesting that a regular daily co-administration of NSAID does not have an influence on platelet inhibition by aspirin.

Influence of combinations of acetylsalicylic acid, acetaminophen, and diclofenac on platelet aggregation.

Acetylsalicylic acid (aspirin) is often given together with other nonsteroidal anti-inflammatory drugs and acetaminophen. The latter have been accused in epidemiologic studies to cause an increased cardiovascular risk. We have, therefore, analysed the influence of various such drug combinations on platelet aggregation in vitro. Citrated blood was incubated with either 25 microg/ml acetaminophen, 0.5 microg/ml aspirin, 0.04 microg/ml diclofenac, or buffer; followed by a second of the above-mentioned solutions. After a 20 min incubation, platelet aggregation was assessed with a platelet function analyser (PFA-100), which measures the pore closure time (CT) by aggregating platelets. The length of CT reflects the degree of platelet inhibition. Acetaminophen alone did not affect platelet aggregation. Aspirin and diclofenac both increased CT (184+/-69 s, P<0.01 and 196+/-54 s, P<0.001; control 120+/-13 s). Combinations of either aspirin and diclofenac, aspirin and acetaminophen, or diclofenac and acetaminophen increased CT further (290+/-22 s, 281+/-36 s, 288+/-25 s, respectively, P<0.001). The time sequence of drug application was important: when diclofenac or acetaminophen was added before aspirin, platelet aggregation was less inhibited than when given in opposite order, i.e. aspirin prior to diclofenac or acetaminophen. We conclude that acetaminophen by itself does not affect platelet aggregation, but potentiates the antiaggregatory effect of aspirin or diclofenac. Aspirin given before acetaminophen or diclofenac had a more potent antiaggregatory effect than vice versa. These observations may have clinical implications.

Influence of acute alcohol exposure on hemorheological parameters and platelet function in vivo and in vitro.

We have analysed the influence of acute alcohol exposure in vivo and in vitro on blood flow properties and platelet function. 12 healthy male volunteers drank either 4.36 ml red wine/kg body weight (=0.5 g ethanol/kg) or water at 06.00 p.m. under fasting conditions. Blood was drawn immediately before, and 1, 2, 4 and 13 h after alcohol ingestion. Alcohol had a detectable osmotic effect on erythrocytes; the mean cellular volume (MCV) was significantly smaller 1-4 h after ingestion. Whole blood viscosity remained unaffected, but blood viscosity at a standardized Hct of 45% measured at a high shear rate (94.5 s(-1)) was increased 2 h after wine ingestion. In the morning, 13 h after wine drinking, platelet aggregation measured with a platelet function analyser PFA-100 was increased to a greater extent than after water drinking. In vitro, no effect was seen when blood was incubated with 0, 12.5, 25, 50 and 100 mmol/l ethanol for 1 h at 37 degrees C. We conclude that an acute exposure to alcohol has only modest effects on hemorheological parameters and platelet aggregation in vivo and no effect in vitro, which suggests that other factors must be involved in both beneficial and harmful effects of wine drinking.