[Specific cyclo-oxygenase-2 inhibitors in cardiovascular pathology]

Cyclo-oxygenase catalyses the conversion of arachidonic acid and O2 into prostaglandins. Its two isoenzymes, COX-1 and COX-2, have different functions. COX-1 is expressed in constituent form in most tissues where it controls the production of arachidonic acid metabolites which maintain the physiological tissue integrity. By contrast, COX-2 is only induced in response to inflammatory stimuli, resulting in the production of inflammation mediating prostaglandins. Conventional non-steroidal anti-inflammatories inhibit both enzymes in a non-specific manner. The recent development of specific COX-2 inhibitors, which retain the same anti-inflammatory efficacy but do not have the gastric side effects of conventional treatment related to COX-1 inhibition, gives them a greater safety margin. However, coronary events are observed in patients treated with COX-2 inhibitors. This risk, seemingly confirmed at least at higher dosages, has been attributed to a disequilibrium in the balance of thromboxane A2/prostacyclin (TxA2/PGI2) which they induce. Paradoxically, COX-2 inhibitors also have several favorable effects on atheromatous plaque progression and its inflammatory component, not only in vitro but also therapeutically, including situations where platelet activation and arterial thrombosis are predominant, such as in acute coronary syndrome. The salt retention induced by COX-2 inhibitors could also be the origin of an increase in blood pressure, and in susceptible subjects it could provoke cardiac decompensation. These multiple cardiovascular risks tinge the safety profile of COX-2 inhibitors, especially in elderly subjects and those with multiple pathology, for whom extra surveillance is required.