Comparison of Low-Molecular-Weight Heparin (LMWH) and Unfractionated Heparin (UFH) in Combination With Thrombolytic Treatment of Acute Massive Pulmonary Thromboembolism

1. Introduction 1.1. Background Acute pulmonary embolism (PE) is a common and often fatal disease, with an approximately 30% mortality rate without treatment [1]. Treatment is important to reduce mortality and recurrence in acute pulmonary embolism. Anticoagulation is the mainstay of the therapy for acute PE. It decreases the mortality rate to 3 to 8 percent, when effective therapy is instituted as quickly as possible [2, 3]. In those cases, therapeutic options include subcutaneous low molecular weight heparin (SC LMWH), intravenous unfractionated heparin (IV UFH), subcutaneous unfractionated heparin and subcutaneous fondaparinux with or without thrombolysis [3].

In the treatment of acute PE, SC LMWH is at least as effective and safe as IV UFH [4]. In general, compared to IV UFH, SC LMWH associated with lower mortality, fewer recurrent thrombotic events and less major bleeding [5]. Current guidelines recommend the use of SC LMWH for most haemodynamically stable patients with PE and they say that SC LMWH have not been tested in the setting of hypotension and shock [3, 6]. However, it seems to be more feasible to use it because of its advantages such as easy administration route, i.e. SC. We have been using SC LMWHs in the cases with acute PE with or without requirement of thrombolysis in our clinical practice since they were available, because of their advantages for practical use and their use in primary or secondary care settings in the patients with because of PE suspicion just before their admission to our hospital. In our 10 years' clinical experience, we observed comparable hemorrhage risk (3.7% vs 0.7% and 12.1% vs 3.8%, for major and minor hemorrhage risk, respectively) with the use of LMWH plus thrombolysis in the cases with massive PE, even compared the cases treated with LMWH alone without massive PE (7). Yet, there is no head to head study comparing LMWH with UFH in the treatment of massive PE.

The study will evaluate safety of LMWH use with thrombolytic treatment in the management of acute PE.

1.2. Purpose The purpose of this study, because of its practical use such as no need for monitoring, is to demonstrate that SC LMWH, enoxaparin, is to be a safe alternative to IV UFH in the management of acute PE cases, who require thrombolytic treatment, in combination with thrombolytic treatment. 2. Study Objectives 2.1. Primary aim The primary aim of the study is to compare the major hemorrhage risk between the use of LMWH plus thrombolytic treatment and UFH plus thrombolytic in the treatment of acute massive PE.

2.2. Secondary Aim The secondary aim of the study is to compare the minor hemorrhage risk and mortality (five day and one year mortality) between the use of LMWH plus thrombolytic treatment and UFH plus thrombolytic in the treatment of acute massive PE. 3. Investigational plan 3.1. Study design This is a single-center randomized study in acute PE patients who require thrombolytic treatment and have no contraindication to use of anticoagulation, comparing safety of SC LMWH versus IV UFH when used with thrombolytic treatment.