What is the mechanism of action of Acetylsalicylic acid (Aspirin) in the management of preeclampsia?

From the Guidelines

Aspirin prevents preeclampsia primarily by inhibiting the enzyme cyclooxygenase (COX), which reduces thromboxane A2 production while preserving prostacyclin synthesis when given at low doses, and should be prescribed at a dose of 100-150 mg/day starting at 12 to 16 weeks of gestation to lower the risk of preeclampsia. This selective inhibition helps restore the balance between these vasoactive compounds, as preeclampsia is characterized by increased thromboxane (causing vasoconstriction and platelet aggregation) and decreased prostacyclin (a vasodilator and inhibitor of platelet aggregation) 1. The evening dosing aligns with the circadian rhythm of blood pressure regulation and maximizes the drug's effectiveness. Aspirin also has anti-inflammatory effects that may help reduce the placental inflammation and immune dysfunction associated with preeclampsia. Additionally, it improves placental development by enhancing trophoblast invasion and spiral artery remodeling, which are often impaired in preeclampsia.

Key Points

• Aspirin should be started early in pregnancy before placental pathology is established, as it works preventatively rather than treating established disease.
• The recommended dose of aspirin is 100-150 mg/day, with a dosage of 162 mg/day being acceptable in some cases.
• Aspirin has been shown to reduce the risk of preeclampsia, preterm birth, and intrauterine growth restriction (IUGR) in women at high risk for preeclampsia 1.
• The use of aspirin in pregnant women with type 1 or type 2 diabetes has been recommended to lower the risk of preeclampsia, with a meta-analysis showing that low-dose aspirin >100 mg is required to reduce preeclampsia 1.

Clinical Considerations

• Aspirin should be prescribed to pregnant individuals with type 1 or type 2 diabetes starting at 12 to 16 weeks of gestation to lower the risk of preeclampsia.
• Individuals with gestational diabetes mellitus (GDM) may be candidates for aspirin therapy for preeclampsia prevention if they have a single high risk factor or multiple moderate risk factors.
• The US Preventive Services Task Force recommends using low-dose aspirin as a preventive medication at 12 weeks of gestation in individuals at high risk for preeclampsia, including those with type 1 or type 2 diabetes 1.

From the Research

Mechanism of Action of Acetylsalicylic Acid (Aspirin) in Preeclampsia Management

The mechanism of action of acetylsalicylic acid (aspirin) in the management of preeclampsia involves:

• Inhibition of thromboxane A2 production, which is a vasoconstrictor that can contribute to the development of preeclampsia 2
• Correction of the pathologic increase in angiotensin II sensitivity that precedes the clinical development of preeclampsia 2
• Proangiogenic, antithrombotic, and anti-inflammatory effects that favor placentation 3
• Inhibition of platelet activation and excessive release of vasoconstricting thromboxane preceding the onset of the disease 4

Key Findings on Aspirin Dosage and Timing

Key findings on aspirin dosage and timing in the prevention of preeclampsia include:

• A daily dose of 100mg or more is recommended 3
• Aspirin should be started before 16 weeks of pregnancy 3, 4
• Starting treatment before 16 weeks may be more effective in reducing the risk of preeclampsia 4
• Daily ingestion of aspirin before bedtime appears useful 4

Clinical Trials and Studies

Clinical trials and studies have demonstrated that:

• Aspirin is effective in preventing preeclampsia in high-risk patients, mainly those with a history of preeclampsia 5
• Low-dose aspirin is safe with regard to congenital anomalies and fetal, neonatal, and maternal cardiovascular physiologic state and hemostasis 2
• Aspirin 150mg once a day at bedtime is more effective than Aspirin 75mg once a day at bedtime in preventing preeclampsia with similar fetomaternal outcomes 6