Pulmonary embolism (PE) is a critical cardiovascular emergency associated with significant morbidity and mortality. Despite advances in diagnosis and therapeutic strategies, it remains a leading preventable cause of cardiovascular death.1
Mortality rates vary significantly based on initial risk stratification. High-risk patients, characterised by haemodynamic instability or cardiac arrest, experience death rates exceeding 25%, whereas intermediate- and low-risk patients exhibit lower acute mortality, but maintain a risk of deterioration and chronic complications.1,2
Risk stratification is paramount in PE management, determining subsequent clinical decisions. Key parameters include clinical risk scores, right ventricular (RV) function and biomarkers such as troponin and natriuretic peptides.
Effective risk stratification is critical to identifying patients who might benefit from reperfusion therapy.1
Systemic thrombolysis remains the guideline-recommended first-line therapy for high-risk PE owing to its efficacy in rapidly reducing RV strain and pulmonary artery pressures.
However, despite clear guidelines, systemic thrombolysis is markedly underused in clinical practice. Recent German nationwide data highlighted thrombolysis rates as low as 23% in haemodynamically unstable patients, consistent with other registries such as RIETE.3,4
Underuse of thrombolysis is primarily attributed to the perceived risk of severe bleeding complications, especially intracranial haemorrhage, and concerns regarding patient-specific contraindications including advanced age, recent surgery and active malignancy.3,5
While systemic thrombolysis is effective, it is associated with a risk of substantial bleeding, which complicates clinical decision-making. The landmark PEITHO trial demonstrated improved haemodynamic outcomes but with a major bleeding rate of approximately 11%, including intracranial haemorrhages.6 In addition, the trial did not demonstrate significant mortality benefits for intermediate-risk, normotensive patients, further complicating clinical decisions.7
To address these limitations, catheter-directed therapies (CDTs) have emerged as promising alternatives. Currently, we are experiencing a golden era of clinical studies exploring the role of CDTs for pulmonary embolism, with numerous recent and ongoing trials transforming clinical practice. We are beginning to accumulate robust evidence from randomised controlled trials evaluating catheter-based techniques.
Recently, the PEERLESS randomised controlled trial compared large-bore mechanical thrombectomy versus catheter-directed thrombolysis in intermediate-risk PE patients. Results demonstrated significantly better outcomes with large-bore mechanical thrombectomy, notably lower rates of clinical deterioration (1.8% versus 5.4%; P=0.04), fewer intensive care unit admissions and shorter hospital stays, without increased bleeding or mortality risks compared to catheter-directed thrombolysis.7 However, the trial had limitations, including its open-label design, variability in CDT protocols and short 30-day follow-up, which may affect generalisability.
Similarly, high-quality registry data such as FLASH (using the FlowTriever system [Inari Medical]) and STRIKE-PE (using the Indigo Lightning 12/Flash system [Penumbra]) show substantial improvements in haemodynamic parameters and symptomatic relief, with consistently low major adverse event rates below 4%, although these are observational studies.8,9
Currently, ultrasound-accelerated thrombolysis is being evaluated in the ongoing HI-PEITHO trial, which will provide valuable data regarding its effectiveness in intermediate- to high-risk PE patients.10
Other ongoing trials, such as PEERLESS II and the recently initiated TORPEDO-NL (mechanical thrombectomy versus fibrinolysis in high-risk PE), are expected to provide more definitive evidence to guide clinical practice.11
The establishment and proliferation of multidisciplinary teams for PE management is increasingly recognised, with numerous centres worldwide implementing pulmonary embolism response teams (PERTs).
However, PERT adoption remains highly variable, and the lack of standardised protocols challenges a broader implementation across diverse hospital settings. Observational studies demonstrate that structured PERT pathways significantly reduce major complications, including bleeding, and improve overall survival.12
One of the main goals is establishing time-sensitive intervention strategies in acute PE. Hence, early initiation of reperfusion therapy and advanced haemodynamic support, including mechanical circulatory support, such as veno-arterial extracorporeal membrane oxygenation, is associated with better survival outcomes.13
However, optimal timing and thresholds for these interventions require further clarification through ongoing research.
Finally, long-term morbidity following acute PE, described as post-PE syndrome, remains an area of clinical importance.14
Approximately half of PE survivors experience persistent symptoms, including dyspnoea, exercise intolerance and, in severe cases, chronic thromboembolic pulmonary hypertension.14
Structured follow-up programmes incorporating regular echocardiographic evaluations, cardiopulmonary exercise testing and systematic screening for chronic thromboembolic pulmonary hypertension are recommended to promptly identify and manage these chronic complications.
However, such follow-up approaches are not yet widely implemented, and more data are needed to determine the most effective long-term management strategies to improve patient quality of life and outcomes.
In conclusion, the treatment landscape for pulmonary embolism is at a turning point. Traditional reliance on systemic thrombolysis is being increasingly complemented by catheter-based techniques supported by structured multidisciplinary teams and refined risk stratification strategies.
Ongoing randomised trials will be critical in shaping future guidelines and clinical practice, ultimately aiming to enhance patient outcomes through individualised and timely therapeutic interventions.