The Bottom Line:
Only one of the phase 3 clinical trials investigating the use of new direct oral anticoagulants in patients with VTE reported efficacy results for the subgroup of patients with acute PE and RV dysfunction. Among patients with elevated NT‐proBNP levels, recurrent VTE occurred in 15 of 454 patients in the edoxaban cohort and in 30 of 484 patients in the warfarin group.
A new trial, the Pulmonary Embolism International Trial (PEITHO‐II) will focus on the safety, efficacy and cost‐effectiveness of dabigatran in the treatment of patients with acute intermediate‐risk PE. Patients will be treated with low molecular weight heparin for at least 72 hours followed by dabigatran treatment for 6 months.
References: Klock FA et al. Management of intermediate–risk pulmonary embolism: uncertainties and challenges. Eur J Haematol. 2015 Dec;95(6):489-97. doi: 10.1111/ejh.12612. Epub 2015 Jul 15.
Link to current trial (still recruiting patients): https://www.escardio.org/Working-groups/Working-Group-on-Pulmonary-Circulation-and-Right-Ventricular-Function/Education/peitho-2
A. The Pulmonary Embolism Thrombolysis Trial (PEITHO) compared, in a double‐blind manner, fibrinolysis with tenecteplase plus heparin vs. placebo plus heparin in 1005 patients with acute PE. Eligible patients had RV dysfunction, plus myocardial injury; that is, they were at intermediate‐high risk of an adverse early outcome. The primary outcome, a composite of all‐cause death or hemodynamic decompensation/collapse, was significantly reduced with tenecteplase. On the other hand, there was an increased incidence of hemorrhagic stroke after fibrinolytic treatment with tenecteplase; major non‐intracranial bleeding events were also increased in the tenecteplase group compared with placebo. This study strongly argues against the standard application of thrombolysis in hemodynamically stable PE patients.
B. Catheter‐directed techniques are considered an alternative to surgery. The safety and efficacy of pharmacomechanical fibrinolysis is supported by the results of a recent trial which enrolled 150 patients with submassive (intermediate‐risk) or massive (high‐risk) PE. Due to the lack of high‐quality studies in patients with PE in general as well as in patients with intermediate‐risk PE specifically, the safety and efficacy of these interventions remain unknown.
New non‐vitamin K‐dependent oral anticoagulants (NOACs), in particular direct factor IIa (thrombin) and factor Xa inhibitors, were developed and tested in large phase‐3 randomized clinical trials. A meta‐analysis of the phase III clinical trials on VTE showed that new oral anticoagulants were associated with a significantly lower risk of major as well as fatal hemorrhage compared to VKA treatment. The experience with NOACs in current trials on intermediate risk PE is limited.