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

• Published in: Basic & clinical pharmacology & toxicology 2020-08, Vol.127 (2), p.132-141
• Main Authors: Mirabito Colafella, Katrina M., Neuman, Rugina I., Visser, Willy, Danser, A. H. Jan, Versmissen, Jorie
• Format: Article
• Language: English
• Subjects: Aspirin; Aspirin - administration & dosage; Aspirin - therapeutic use; Biochemical tests; COX-2 inhibitors; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - therapeutic use; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - therapeutic use; Developmental stages; Dosage; Dose-Response Relationship, Drug; Eclampsia; Female; Health services; Humans; hypertension; Minireview; MINIREVIEWS; Pathogenesis; Placenta; Pre-Eclampsia - drug therapy; Pre-Eclampsia - enzymology; Pre-Eclampsia - prevention & control; Preeclampsia; Pregnancy; Prevention; pre‐eclampsia; Prostaglandin endoperoxide synthase; Prostaglandins; Prostaglandin‐Endoperoxide Synthases; Risk management; Risk reduction
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.13308

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.