Effectiveness and Safety of Tokishakuyakusan in Hospitalized Patients With Hypertensive Disorders of Pregnancy: A Nationwide Retrospective Cohort Study Using Japanese Claims Data

Background: Hypertensive disorders of pregnancy (HDP) are life-threatening conditions. Although antihypertensive medications effectively control blood pressure, they do not target the underlying pathophysiology of HDP. Tokishakuyakusan, a traditional Kampo medicine, has demonstrated the potential to improve uteroplacental circulation in experimental HDP models; however, its clinical effectiveness remains unclear. This study investigated the real-world effectiveness and safety of Tokishakuyakusan in hospitalized patients with HDP. Methods: This retrospective cohort study analyzed data from the Japanese Diagnosis Procedure Combination database collected between 2014 and 2023. Pregnant women admitted at 20 weeks of gestation or later with a diagnosis of HDP were included if they received oral antihypertensive therapy within the first 3 days of hospitalization. Patients were classified into two groups based on whether they received Tokishakuyakusan within the first 3 days of hospitalization. The primary outcome was the administration of intravenous magnesium sulfate or nicardipine. Secondary outcomes included maternal adverse events and preterm birth. Multivariate logistic regression was performed for statistical analysis. Results: Overall, 11,264 women met the inclusion criteria, including 85 who received Tokishakuyakusan in combination with antihypertensive therapy, and 11,179 who received antihypertensive drugs alone. Tokishakuyakusan use was not significantly associated with the primary outcome [adjusted odds ratio (aOR) 1.07, 95% confidence interval (CI) 0.69–1.68], maternal adverse events (aOR: 0.82, 95% CI: 0.52–1.27), or preterm birth (aOR: 0.84, 95% CI: 0.51–1.38). Conclusions: Tokishakuyakusan was infrequently prescribed but appeared to be safe in women with HDP. No significant association between reduced disease progression and preterm birth was identified, although the small sample size was a limiting factor.