Contemporary role of systemic thrombolysis in the management of acute pulmonary embolism

Acute pulmonary embolism (PE) remains a leading cause of cardiovascular mortality worldwide. Effective management hinges on accurate risk stratification - classifying patients as high, intermediate, or low risk - to guide reperfusion strategies. This review evaluates the contemporary role of systemic thrombolysis, with a focus on the balance between rapid hemodynamic restoration and the risk of catastrophic hemorrhage. For high-risk PE characterized by hemodynamic instability, systemic thrombolysis remains the gold standard, offering a significant survival benefit that outweighs bleeding risks. Conversely, in intermediate-risk PE, it has been demonstrated that while full-dose thrombolysis prevents hemodynamic decompensation, it is associated with a significant increase in major bleeding and intracranial hemorrhage. Consequently, current guidelines generally support a "rescue thrombolysis" strategy rather than routine, up-front administration in this population. Encouragingly, recent small studies appear to demonstrate reduced-dose protocols that maintain efficacy while minimizing risk of major bleeding. While the acute effects of thrombolysis on hemodynamics are clear, there is conflicting evidence regarding the impact of thrombolysis on long-term sequelae such as chronic thromboembolic pulmonary hypertension (CTEPH). Ultimately, clinical decision-making must prioritize immediate hemodynamic risk while carefully evaluating contraindications to minimize adverse outcomes.