Background: Preeclampsia is a major hypertensive disorder of pregnancy, which may lead to severe complications, particularly in the first two weeks of the postpartum period. During the postpartum period, blood pressure levels remain high, often increasing to levels higher than those experienced during pregnancy. Furosemide, a fast-acting diuretic, reduces the intravascular volume overload and may represent an alternative to accelerate the normalization of blood pressure levels.
Objective: To evaluate the effectiveness of furosemide compared to placebo for blood pressure control in the postpartum period in women with severe preeclampsia.
Study design: In a triple-masked placebo-controlled randomized clinical trial, women in the postpartum period with de novo preeclampsia with severe features or eclampsia diagnosed during pregnancy and adequate diuresis, who had received magnesium sulfate, were randomized to receive furosemide (40 mg/day orally for five days) or placebo. The primary outcomes were mean blood pressure levels. Secondary outcomes were: frequency of severe hypertensive episodes, a continued need for antihypertensives, number of antihypertensives used to control blood pressure, length of hospital stay, adverse effects and maternal complications. A sample size of 120 patients was estimated, 60 in each arm of the study, based on the estimated difference between the mean systolic pressure of 142±12mmHg for the furosemide group and 153±19mmHg for the placebo group.
Results: Between June 20 and November 30, 2014, 271 women were screened and 120 were randomized to furosemide or placebo, with 118 being included in the final analysis (58 in the furosemide group and 60 in the placebo group). Most characteristics were similar in both groups. Mean daily systolic and diastolic pressure was lower in the furosemide group (P<0.001) and there were fewer episodes of severe hypertension on the second (P=0.04) and fifth (P=0.04) days. In addition, shorter time was required until blood pressure was controlled (P=0.01) in the furosemide group.
Conclusion: Compared to placebo, 40 mg/day of oral furosemide in patients with preeclampsia in the postpartum period reduced mean daily systolic blood pressure in 1st and 5th days and mean daily diastolic blood pressure in 1st, 2nd and 5th days and the time required until blood pressure is controlled.
The optimal aspirin dose for preeclampsia prevention remains controversial, with international guidelines lacking consensus on the most effective regimen. Aspirin is a proven intervention for reducing the risk of preeclampsia, particularly when initiated early in pregnancy. Its benefits stem from the selective inhibition of cyclooxygenase-1 (COX-1), reducing thromboxane A2 synthesis while preserving prostacyclin production, thereby restoring the vascular balance essential for placental health. A dose-response relationship has been established, with doses ≥100 mg showing significantly greater efficacy than lower doses. Furthermore, aspirin's pharmacological effects remain highly specific to COX-1 at the 162 mg dose, minimizing concerns about broader prostaglandin inhibition. Emerging evidence suggests that certain patient factors, such as altered pharmacokinetics during pregnancy or obesity, may reduce aspirin's effectiveness at lower doses (e.g., 81 mg). In these studies, aspirin resistance was successfully overcome with a 162 mg dose. While concerns regarding safety at this dose have been raised, contemporary randomized controlled trials utilizing a 150 mg dose have shown no increase in adverse effects compared to placebo. As such, current evidence increasingly supports 162 mg as the optimal dose for preeclampsia prevention, offering greater effectiveness than the commonly used 81 mg dose, without significant evidence of increased risk.
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