Evolution to low-dose NSAID therapy.

All NSAIDs are to varying degrees associated with gastrointestinal, cardiovascular and renal adverse effects (AEs). Differences in selectivity for inhibition of the COX isozymes (COX-1/COX-2) have been used as an indicator of the likelihood of experiencing an AE, but the measure of 'selectivity' commonly used is less than desirable, and selectivity has not yielded unequivocal superior safety. Recent guidelines recommend that NSAIDs be used at the lowest effective dose and for the shortest period of time. In response, 'low-dose' NSAID formulations have been developed. Such formulations may help by reducing overall systemic exposure, thereby reducing the frequency or severity of AEs. It seems timely to review the need, rationale and application of such an approach.