Glycemic Control and Aspirin Resistance in Patients Taking Low-Dose Aspirin for Pre-eclampsia Prevention

To assess the association between aspirin and glycemic control in diabetic, pregnant patients, and the risk for aspirin resistance in those with poor glycemic control across gestation taking low-dose aspirin (LDA) for pre-eclampsia (PEC) prevention.

We performed a secondary analysis of samples collected during the Maternal-Fetal Medicine Units trial of LDA for PEC prevention. A subset of insulin-controlled diabetic patient samples on placebo or 60 mg aspirin daily were evaluated. Glycosylated hemoglobin was measured at randomization, mid-second trimester, and third trimester time points. Thromboxane B₂ (TXB₂) measurements were previously assessed as part of the original study. Primary outcome was the effect of LDA on glycosylated hemoglobin levels compared with placebo across gestation.

Levels of glycosylated hemoglobin increased across gestation in the placebo group (2,067.7 [interquartile range, IQR: 1,624.6-2,713.5 µg/mL] vs. 2,461.9 [1,767.0-3,209.9 µg/mL] vs. 3,244.3 [2,691.5-4,187.0 µg/mL]; p < 0.01) compared with no difference in levels of glycosylated hemoglobin across gestation in the LDA group (2,186.4 [IQR: 1,462.3-3,097.7 µg/mL] vs. 2,337.1 [1,327.7-5,932.6 µg/mL] vs. 2,532.9 [1,804.9-5,511.8 µg/mL]; p = 0.78). Higher levels of glycosylated hemoglobin were associated with increased TXB₂ levels prior to randomization (r = 0.67, p < 0.05). Incomplete TXB₂ was higher in pregnancies with increasing levels of glycosylated hemoglobin compared with those with decreasing levels of glycosylated hemoglobin across gestation (69.2 vs. 18.1%, p = 0.02).

LDA exposure may be beneficial to glycemic control in this patient population. Additionally, poor glycemic control is associated with a higher level of TXB₂ in diabetic pregnant patients on LDA. Higher doses of aspirin may be required in these patients to prevent development of PEC.

· Low-dose aspirin may improve glycemic control.. · Poor glycemic control increases risk for aspirin resistance.. · Higher doses of aspirin may be required for pre-eclampsia prevention..