Results of a phase 4 study involving an early switch from heparin to dabigatran in patients with acute intermediate-risk pulmonary embolism (PE) indicated this approach was effective and safe in this population. The study results were recently published in The Lancet Haematology.
The phase 4 PEITHO-2 trial (ClinicalTrials.gov Identifier: NCT02596555) was a single-arm, multinational trial occurring at 42 hospitals across Europe. Enrolled patients had symptomatic intermediate-risk PE. They were treated with parenteral low molecular-weight or unfractionated heparin for 72 hours, followed by a switch to oral dabigatran for 6 months, dosed at 150 mg 2 times per day. Patients could continue with oral dabigatran depending on physician discretion. The primary efficacy outcome was recurrence of symptomatic venous thromboembolism (VTE) or PE-associated fatality within 6 months of follow-up.
The trial was terminated early after a change in sample size based on the predefined interim analysis. A total 402 patients were included in intention-to-treat analyses of this study. Patients had a median age of 69.5 years (interquartile range [IQR], 60.0-78.0). The median study follow-up occurred at 217 days (IQR, 210-224), with a 92% rate of protocol adherence.
The rate of occurrence of the primary outcome, symptomatic VTE or PE-related fatality at 6 months, was 2%. This was significantly lower (P <.0001) than the highest predicted probability of 6.1% for this population for this outcome. All events related to this outcome involved patients with intermediate- to high-risk PE. At the time of the report’s writing, recurrent PE was reported in 1% of patients, recurrent deep-vein thrombosis was reported in less than 1% of patients, and PE-related death was reported in less than 1% of patients. Any-cause mortality was reported in 2% of patients within the first 6 months.
At 6 months, safety analysis (402 patients) revealed that the presence of 1 or more major bleeding events was reported in 3% of patients, and 4% of patients had 1 or more clinically relevant nonmajor bleeding events reported. A fatal hemorrhage was reported in 1 patient prior to receiving dabigatran. The presence of at least 1 serious adverse event in the first 30 days was reported in 9% of patients, while the rate was 18% within 6 months.
“In conclusion, this prospective multinational trial focusing on patients with intermediate-risk pulmonary embolism found that a management strategy of early switch from heparin to dabigatran after rigorous clinical assessment of stabilisation at 72 h was both effective and safe,” the study investigators concluded in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Klok FA, Toenges G, Mavromanoli AC, et al; for the PEITHO-2 investigators. Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial. Lancet Haematol. 2021;8(9):e627-e636. doi:10.1016/S2352-3026(21)00203-9