USE OF CLOPIDOGREL IN PREGNANCY

Clopidogrel is an antiplatelet prodrug, the active metabolite of which inhibits ADP-mediated platelet aggregation through irreversible binding to the platelet P2Y12 receptor. It is indicated for the treatment of transient ischaemic attack, minor ischaemic stroke, and the prevention of atherothrombotic events (including myocardial infarction and stroke) in patients with predisposing factors or after percutaneous coronary intervention.

Maternal cardiovascular conditions (e.g., coronary artery disease, prior stroke, antiphospholipid syndrome) may independently increase the risk of miscarriage, preterm delivery, and impaired fetal growth, particularly when disease control is suboptimal. Low molecular weight heparin (LMWH) is usually the first-line anticoagulation in pregnancy due to limited placental transfer; however, in some circumstances, use of other antithrombotic agents may be necessary. The European Society of Cardiology (ESC) guidelines state that when dual antiplatelet therapy (DAPT) is indicated, clopidogrel is recommended as the P2Y12 inhibitor of choice in combination with low-dose aspirin.

Published data on clopidogrel exposure in pregnancy is limited and consist primarily of case reports and a small cohort study collectively describing fewer than 100 pregnancies (including 74 with confirmed first trimester exposure). UKTIS has prospectively collected outcome data for 15 exposed pregnancies, including 11 exposed in at least the first trimester. The cohort study signalled a possible 4-fold increased risk of overall major congenital malformation; however, this signal arose from a hypothesis-generating analysis without correction for multiple testing and was not specific to any malformation pattern. The findings are therefore inconclusive and require confirmation in higher-quality studies. There were no congenital malformations among the 11 first trimester-exposed pregnancies reported to UKTIS. Data are too limited to assess the risks of other adverse pregnancy outcomes; however, case reports of continued therapy throughout pregnancy mainly describe uneventful outcomes.

Use of clopidogrel in the peripartum period may increase the risk of maternal bleeding complications. Antiplatelet therapy is associated with an increased risk of neuraxial (spinal/epidural) haematoma, and guidelines for neuraxial anaesthesia recommend discontinuation of clopidogrel for approximately 5–7 days prior to procedures such as epidural placement to reduce bleeding risk. Continuation of therapy near delivery may therefore increase the risk of obstetric haemorrhage, including postpartum haemorrhage. Discontinuation of clopidogrel one week before delivery to minimise the risk of bleeding complications has been described in a case report.

No additional fetal monitoring is required solely due to clopidogrel exposure. However, given the paucity of pregnancy safety data, women should be encouraged to attend their routine anomaly scan (at 18-22 weeks of pregnancy). As maternal cardiovascular pathology independently increases adverse pregnancy outcome risks, individualised risk assessment is essential when counselling and managing pregnant women requiring antiplatelet therapy. Discussion of individual cases with UKTIS is recommended.