Application of Loading Dose Warfarin in Postpartum Women with Pulmonary Embolism – a Prospective, Randomized, Double-Blind Trial

Weifeng Huang,1,* Huiqin Sun,2,* Lu Zhou,3 Yan Chen,4 Yan Huo5 1Department of Critical Care Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 4Department of Pharmacy, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Pharmacy, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Chen, Department of Pharmacy, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Email [email protected] Yan Huo, Department of Pharmacy, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Email [email protected]: Warfarin is usually used in a fixed loading dose regimen, which may increase the risk of bleeding or prolong the time to reach standard dose. The aim of the study is to compare the efficacy and safety of loading dose versus maintenance dose of warfarin therapy in postpartum women with pulmonary embolism (PE) under the guidance of clinical pharmacogenetic information.Patients and Methods: A total of 64 postpartum women with PE were recruited from September 2022 to August 2023. Participants were randomly divided 1:1 into two groups using a random-number table patients in the experimental group received a regimen combining the initial 1 to 3 days loading dose with the International Warfarin Pharmacogenetics Consortium (IWPC) model. Patients in the control group only received a regimen guided by the IWPC model for the initial 1 to 3 days. Starting from day 4, the warfarin dose was adjusted according to the international normalized ratio (INR). The primary outcome was first time to therapeutic INR (2.0– 3.0).Results: The study found that the median time to first reach the therapeutic INR was 5.5 days in the experimental group compared to 7 days in the control group (p=0.002). The median time within therapeutic range (TTR) was 97.24% in the experimental group compared to 95.50% in the control group (p=0.001). The difference in adverse events showed no statistical significance between the two groups (P > 0.05).Conclusion: The study could provide ideas for the precise treatment of warfarin in postpartum women with PE. The integration of warfarin loading doses guided by pharmacogenetics into clinical practice can enhance decision-making, optimize patient outcomes, and reduce adverse events.Keywords: warfarin, loading dose, maintenance dose, IWPC, postpartum women