Managing high-risk pulmonary embolism
Systemic thrombolysis, specifically using recombinant tissue plasminogen activator (rtPA), is the current gold standard treatment for high-risk pulmonary embolism (PE).
High-risk PE typically involves hemodynamically unstable patients presenting with conditions such as low blood pressure, cardiac arrest, or the need for mechanical circulatory support. There is a spectrum of severity within high-risk PE, making it a complex condition to manage, especially since many patients have comorbidities like anemia or active cancer, complicating treatment.
In high-risk PE, the therapeutic priority is rapid hemodynamic stabilization and restoration of pulmonary blood flow to prevent cardiovascular collapse. Systemic thrombolysis acts quickly, reducing pulmonary vascular resistance and obstruction within hours.
The PEITHO trial demonstrated the ability of systemic thrombolysis to reduce all-cause mortality and hemodynamic collapse within 7 days.
However, this benefit comes at the cost of increased bleeding risk, including a 10% rate of major bleeding and a 2% risk for intracranial hemorrhage. The risk of bleeding is also related to the type of thrombolytic agent, with Tenecteplase being strongly associated with a higher risk of bleeding, while alteplase shows no increase in the risk of major bleeding.
New strategies like reduced-dose thrombolysis offer comparable efficacy and improved safety, as demonstrated in ongoing trials like PEITHO-3, which aim to optimize the balance between efficacy and bleeding risk.
Systemic thrombolysis remains the best option for most patients because it is widely available, easily administered with intravenous infusion, and at a limited cost.
While recombinant tissue plasminogen activator (rtPA) might not be optimal for all patients, there is not enough evidence to replace it as a first-line treatment.
Alternative treatments such as catheter-directed therapies, extracorporeal membrane oxygenation (ECMO), and surgical embolectomy are emerging as promising options, especially for patients who do not respond to or cannot receive rtPA. Mechanical treatments offer benefits in reducing clot burden and stabilizing patients, but they come with their own challenges.
ECMO can stabilize patients who are in shock or cardiac arrest, buying time for the clot to resolve or for further interventions like surgery or catheter-based treatments. However, it is an invasive procedure requiring cannulation of large blood vessels, often involving significant resources and expertise.
Catheter-directed thrombolysis is a minimally invasive technique where a catheter is inserted directly into the pulmonary artery to deliver thrombolytic drugs at lower doses. This method allows for more targeted treatment of the clot, reducing the risk for systemic bleeding that comes with higher doses of thrombolytic agents used in systemic therapy.
Catheter-directed treatment and surgical options are only available in specialized centers, require expertise and training, and are also extremely expensive.
Existing studies on catheter-directed therapies often focus on surrogate endpoints, such as right-to-left ventricular ratio changes, rather than clinical outcomes like mortality. Retrospective data suggest that catheter-directed therapies may reduce in-hospital mortality compared with systemic therapies, but they also increase the risk of intracranial bleeding, post-procedure complications, and device-related events.
The FLAME study reported a 23% rate of device-related complications and 11% major bleeding in patients treated with catheter-directed therapies.
When catheter-based treatment fails, surgical pulmonary embolectomy is a last-resort option.
