Aspirin for the prevention and treatment of pre-eclampsia: A matter of COX-1 and/or COX-2 inhibition?

Since the 1970s, we have known that aspirin can reduce the risk of pre-eclampsia. However, the underlying mechanisms explaining this risk reduction are poorly understood. Both cyclooxygenase (COX)-1- and COX-2-dependent effects might be involved. As a consequence of this knowledge hiatus, the optimal dose and timing of initiation of aspirin therapy are not clear. Here, we review how (COX-1 versus COX-2 inhibition) and when (prevention versus treatment) aspirin therapy may interfere with the mechanisms implicated in the pathogenesis of pre-eclampsia. The available evidence suggests that both COX-1- and COX-2-dependent effects play important roles in the early stage of aberrant placental development and in the next phase leading to the clinical syndrome of pre-eclampsia. Collectively, these data suggest that high-dose (dual COX inhibition) aspirin may be superior to standard low-dose (selective COX-1 inhibition) aspirin for the prevention and also treatment of pre-eclampsia. Therefore, we conclude that more functional and biochemical tests are needed to unravel the contribution of prostanoids in the mechanisms implicated in the pathogenesis of pre-eclampsia and the potential of dual COX and/or selective COX-2 inhibition for the prevention and treatment of pre-eclampsia. This information is vital if we are to deduce the suitability, optimal timing and dose of aspirin and/or a specific COX-2 inhibitor (most likely using modified forms that do not cross the placenta) that can then be tested in a randomized, controlled trial instead of the current practice of empirical dosing regimens.