What is the role of thrombolytics in hemodynamically stable Pulmonary Embolism (PE)?

From the Guidelines

Thrombolytics are generally not recommended for hemodynamically stable pulmonary embolism (PE) patients, and anticoagulation with direct oral anticoagulants (DOACs) or traditional therapy with low molecular weight heparin bridging to warfarin is the standard treatment. The most recent and highest quality study, the 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism 1, suggests that thrombolytic therapy leads to faster improvements in pulmonary obstruction, but is associated with a significant risk of severe bleeding and intracranial hemorrhage.

The guidelines recommend reserving thrombolytic therapy for patients with high-risk PE who develop hemodynamic instability, persistent hypoxemia, or right ventricular dysfunction with clinical deterioration. In normotensive patients with intermediate-risk PE, defined as the presence of RV dysfunction and elevated troponin levels, the impact of thrombolytic treatment was investigated in the Pulmonary Embolism Thrombolysis (PEITHO) trial, which found that thrombolytic therapy was associated with a significant reduction in the risk of hemodynamic decompensation or collapse, but also an increased risk of severe extracranial and intracranial bleeding 1.

Key points to consider in the management of hemodynamically stable PE patients include:

• Anticoagulation with DOACs, such as apixaban or rivaroxaban, or traditional therapy with low molecular weight heparin bridging to warfarin, as the standard treatment
• Reserving thrombolytic therapy for patients with high-risk PE or those who develop hemodynamic instability
• Careful risk-benefit assessment in select cases of submassive PE with extensive clot burden, right ventricular dysfunction on imaging, and elevated cardiac biomarkers but without hemodynamic compromise
• Close monitoring in an intensive care setting if thrombolytics are administered, with immediate discontinuation if bleeding complications occur, as recommended by the 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism 1.

Overall, the management of hemodynamically stable PE patients should prioritize anticoagulation and reserve thrombolytic therapy for high-risk cases or those with clinical deterioration, as supported by the most recent and highest quality evidence 1.

From the Research

Thrombotics in Hemodynamically Stable PE

• The use of thrombolysis in hemodynamically stable patients with acute pulmonary embolism (PE) remains controversial, with some studies suggesting an increased risk of major bleeding and intracranial hemorrhage 2.
• A meta-analysis of randomized trials found that patients randomized to thrombolysis had a significant increased risk for major bleeding (5.9% vs 1.9%) and an increased risk for intracranial hemorrhage (1.74% versus 0.6%) 2.
• However, the same meta-analysis found a non-significant reduction in all-cause death (1.74% vs 2.51%) and a significant reduction in recurrent PE (1.1% vs 2.5%) in favor of thrombolysis compared with heparin 2.
• The number needed to harm (NNH) to cause a major bleeding or an intracranial hemorrhage were 27 and 91 patients, respectively, while the number needed to treat (NNT) to avoid one death was 125 patients 2.

Anticoagulation Therapy

• Low-molecular-weight heparin (LMWH) is at least as effective as unfractionated heparin (UFH) in the treatment of PE, with a similar risk of bleeding 3.
• LMWH offers more predictable pharmacokinetics and anticoagulant effects, making it a preferred choice for anticoagulation therapy in hemodynamically stable PE patients 3, 4.
• Direct oral anticoagulant drugs (DOACs) are also becoming a popular choice for anticoagulation therapy in PE patients, due to their simplicity and effectiveness 5.
• However, many relative contraindications to DOACs were exclusion criteria in clinical trials, and therefore LMWHs will continue to play an important role in initial PE treatment 5.

Risk Stratification

• Risk stratification is essential to drive clinical management in hemodynamically stable PE patients, and simple and routine tests such as oxygen saturation or respiratory rate can improve risk stratification 6.
• The 2014 European Society of Cardiology (ESC) risk stratification strategy can be improved by adding oxygen saturation or respiratory rate to identify patients at increased risk of death 6.
• Patients with oxygen saturation in air of < 88% may be at increased risk of death and potentially candidates for more aggressive treatment 6.