Effects of Meloxicam on Platelet Function in Healthy Adults: A Randomized, Double‐Blind, Placebo‐Controlled Trial

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1), thereby inhibiting platelet function via blockade of thromboxane A2 (TxA2) formation, and COX-2, the enzyme that mediates inflammatory responses. Meloxicam is a relatively COX-2-selective anti-arthritis drug that shows significant TxA2 inhibition, albeit less than traditional NSAIDs. A randomized, double-blind, placebo-controlled trial was conducted in 79 healthy adults to compare the effects of once-daily therapeutic (7.5 mg, 15 mg) and supratherapeutic (30 mg) doses of meloxicam with extended-release indomethacin (Indo-ER 75 mg once daily) on bleeding time, TxA2 formation, and platelet aggregation. The authors measured platelet aggregation to COX-1-dependent (ADP arachidonate) and COX-1-independent (high-dose collagen) agonists, bleeding time, serum TxB2, and clotting times (aPTT and PT) after 8 days' administration and at 3 and 6 hours after steady-state dosing. Meloxicam significantly decreased TxB2 production compared with placebo in a dose-dependent fashion, reaching a peak of 77% inhibition 6 hours after 30 mg meloxicam; Indo-ER blocked TxB2 formation by 96% at the same time point. However, neither acute nor 8 days' administration of meloxicam at any dose caused a significant increase in bleeding time or inhibition of platelet aggregation to any agonist when compared with placebo. By contrast, Indo-ER significantly increased the bleeding time and inhibited platelet aggregation to COX-1-dependent agonists 6 hours after dosing. Clotting times were unaffected by any drug. It was concluded that unlike nonselective NSAIDs, meloxicam's blockade of TxA2 formation (even at supratherapeutic doses) does not reach levels that result in decreased in vivo platelet function, as measured by bleeding time and aggregometry. In this study of healthy subjects, meloxicam did not interfere with platelet-mediated hemostasis.

Serum thromboxane B2 (TXB2) Determination is Influenced by Sample Incubation Temperature in Healthy Beagle Dogs

“…The measurement of serum TXB 2 production by platelets following blood coagulation is a specific and most frequently used test for evaluation of platelet COX-1 activity in humans and other species (Brideau et al 1996;Blain et al 2002;Gilmer et al 2003;Jones et al 2002;Patrignani et al 1997;Rinder et al 2002;Sessions et al 2005;Van Kraaij et al 2002). Whole blood TXB 2 production is measured from clotted blood samples obtained from the patient after administration of NSAID or after collection of blood into tubes preloaded with NSAID.…”

“…While searching for the literature on normal values of TXB 2 in canine serum and the measurement of serum TXB 2 after NSAID administration, we found inconsistency in the published data, which might influence the results obtained. In some studies (Blain et al 2002;Gilmer et al 2002;Jones et al 2002;McKellar et al 1990;Rinder et al 2002;Streppa et al 2002) blood samples for serum TXB 2 determination were incubated during blood clotting at 37 C for one hour as recommended (Brideau et al 1996;Patrignani et al 1997), whereas other studies (Frelinger et al 2006;Hashimoto et al 2002;Morchon et al 2006;Sunose et el. 2001a;Sunose et al 2001b;Tanus-Santos et al 2000) did not mention the incubation of samples.…”

Rofecoxib does not compromise platelet aggregation during anesthesia and surgery

“…teers and nonsurgical patients have indicated that COX-2 inhibitors have virtually no effect on the gastric mucosa or platelet function. [1][2][3][4] Safety in the perioperative setting has been suggested by the lack of increased intraoperative blood loss in patients receiving this class of drug. 5,6 Despite these favourable findings, many clinicians remain hesitant to administer COX-2 inhibitors perioperatively until there is more definitive evidence that these drugs do not alter platelet function during anesthesia and surgery.…”

“…5,6 Despite these favourable findings, many clinicians remain hesitant to administer COX-2 inhibitors perioperatively until there is more definitive evidence that these drugs do not alter platelet function during anesthesia and surgery. Such evidence may be provided by measuring platelet aggregation 2,7,8 in response to an aggregatory stimulus such as arachidonic acid (AA) or adenosine diphosphate (ADP). Whereas a myriad of potentially offsetting perioperative factors -many of which are not directly related to platelet functionmay affect measurements of blood loss, aggregometry is more sensitive to and more specific for the potential platelet inhibitory effects of a study drug.…”

How beneficial is the use of NSAIDs in stem-cell transplantation?

“…Meloxicam has a long track record of safety and a favorable side-effect profile compared to other dual COX inhibitors. Trials in healthy volunteers showed that meloxicam did not prolong bleeding time or affect platelet aggregation [11]. With regard to the potential gastrointestinal side effects of NSAIDs, meloxicam is very well tolerated [12].…”