Aspirin inhibits cyclo-oxygenase (COX) enzymes by irreversible acetylation, and at lower doses exhibits relative selectivity for COX1, responsible for the synthesis of thromboxane A2 (TXA2), which is a pro-thrombotic and vasoconstrictive eicosanoid. At higher doses, aspirin is also able to inhibit COX2, leading to a reduction in release of the anti-thrombotic and vasodilatory compound prostacyclin (PGI2). Aspirin is able to inhibit platelet aggregation, therefore, by inhibiting TXA2 relatively more than PGI2. Due to its irreversible binding, COX is inhibited in platelets for their lifespan (typically 10-12 days) as, being without a nucleus, they cannot regenerate the enzyme (Patrono 1994). It is now thought that PGI2 acts locally rather than systemically and, in healthy individuals, COX1 may be responsible for the majority of PGI2 production (Kirkby, Lundberg et al. 2012). In patients with atheromatous disease, however, there is greater COX2 expression in diseased vessel walls (Schonbeck, Sukhova et al. 1999) therefore this may not apply in the areas most vulnerable to thrombosis. COX2 selective inhibitors have been associated with increased cardiovascular risk and this appears to be both a dose dependent and class effect (Mukherjee, Nissen et al. 2001, Bhala, Emberson et al. 2013).