Efficacy and safety of early switch to oral anticoagulation in acute intermediate-risk pulmonary embolism

Abstract

Abstract Background Guidelines recommend risk-adjusted management of pulmonary embolism (PE). We investigated whether treatment of acute intermediate-risk PE with parenteral anticoagulation for a short period of 72 hours, followed by switch to a direct oral anticoagulant (dabigatran), is effective and safe. Methods We conducted a prospective multicentre single-arm management trial in patients with intermediate-risk PE (EudraCT Identifier 2015–001830–12). Patients received parenteral heparin, switched to dabigatran 72 hours after diagnosis following standardised clinical assessment. The study was terminated early following sample size adaptation after the predefined interim analysis. Findings From January 2016 through July 2019, 402 patients were enrolled in 9 European countries. Adherence to protocol was 92.0% (Table 1). The primary outcome, recurrent symptomatic venous thromboembolism or PE-related death within 6 months (Table 2), occurred in 7 patients (1.7%; upper bound of right-sided 95% CI 3.2%; p=0.ehab724.192322 for rejecting H0), with all events in the intermediate-high-risk group (2.5%; upper bound of right-sided 95% CI 4.6%). Median duration of hospitalisation for the index event was 6 days, despite the fact that >70% of the patients had intermediate-high-risk PE. The six-month incidence of major bleeding was 2.7%; the only fatal haemorrhage occurred before switch to dabigatran. Interpretation A strategy of early switch from heparin to dabigatran following standardised clinical assessment was effective and safe in intermediate-risk PE. Our results can help to fine-tune guideline recommendations for initial treatment of PE, optimising the use of resources and avoiding prolonged hospitalisation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Federal Ministry of Education and Research; and Boehringer Ingelheim Table 1. Time between diagnosis of pulmonary embolism and switch to dabigatran (N = 402 patients)Table 2. Efficacy and safety outcomes