Thrombectomy Tops Thrombolysis in Pulmonary Embolism Trial

WASHINGTON, DC — Large-bore mechanical thrombectomy is superior to catheter-directed thrombolysis for pulmonary embolism, according to a randomized trial comparing the two interventions. Although there was no difference in major events, mechanical thrombectomy had a list of advantages including faster clinical and hemodynamic improvement.

The study, called PEERLESS, enrolled 550 patients in three countries with intermediate risk of pulmonary embolism according to European Society of Cardiology guidelines. The primary endpoint was a hierarchical win ratio, in which endpoints are ranked and assessed by importance. The treatment arms are compared for each endpoint in sequence from the most important to the least. The number of wins is divided by the number of losses to provide a ratio.

That analysis found a significant advantage for thrombectomy over thrombolysis, even though the rates of hard endpoints such as mortality, major bleeding, or intracranial-hemorrhage, were about the same, according to Wissam A. Jabar, MD, a professor of interventional cardiology at Emory School of Medicine in Atlanta, Georgia, who presented the results here at Transcatheter Cardiovascular Therapeutics 2024.

There were no significant differences between study arms for the first three of the five components, which were all-cause mortality, intracranial hemorrhage, and bleeding. Rather, the differences were driven by the last two endpoints, which were clinical deterioration and intensive care unit admission.

Difference in ICU Admissions

The win ratio of 5.01 produced a highly significant result in favor of mechanical thrombectomy. But when the last endpoint was removed from consideration, the win ratio for the first four endpoints by themselves, which was a prespecified secondary endpoint, fell short of significance.

Patients in the thrombolysis arm were three times more likely to experience clinical deterioration. Within this endpoint, cardiac arrest (0% vs 0.7%), high grade atrioventricular block (0% vs 0.4%), respiratory failure (0% vs 1.1%), and hypotension (1.1% vs 1.4%) were all more common in the thrombolysis group. The need for supplementary oxygen (0.4% vs 0%) was less common in the thrombolysis than the thrombectomy arm.

For postprocedural intensive care unit (ICU) admission, the rate was more than 90-fold higher and the rate for a longer than 24-hour admission was more than two times higher.

Several experts, however, questioned the relevance of ICU admissions for comparing these treatment strategies.

Study Endpoint Criticized

“ICU admission for pulmonary embolism patients is driven by local practice,” said Felix Mahfoud, MD, Chief of Cardiology at University Hospital Basel in Basel, Switzerland. He pointed out ICU admission is a required step in the protocol for thrombolysis at many centers, so a win on this endpoint was inevitable. Without linking ICU admission to specific complications, Mahfoud said it is unclear whether this is a true clinical difference even if more patients did remain in the ICU for more than 24 hours.

Along with a better outcome for thrombectomy on the primary endpoint, patients in this group had less dyspnea, and a higher proportion of those in the thrombolysis group had moderate to severe impairment of right ventricular function on echocardiography. Jabar also pointed out that patients randomized to thrombectomy had both a shorter postprocedural length of stay (3.3 vs 4.0 days) and a shorter total hospital stay (4.5 vs 5.3 days).

Although the thrombectomy group had a lower rate of pulmonary embolism-related 30-day readmissions, the difference was not significantly significant, but the all-cause 30-day readmission rate was significantly lower (3.2% vs 7.9%), said Jabar.

More Trials Needed

Aside from the relevance of the ICU admissions endpoint, Mahfoud posed several other questions about how these results should be interpreted. He expressed uncertainty about whether thrombolysis is the standard of care to which thrombectomy is best compared. When comparing potential options for controlling pulmonary embolism in intermediate-risk patients, he suggested a third treatment arm of anticoagulation might have been helpful as a reference. However, he did praise the PEERLESS trial for demonstrating that thrombectomy is safe relative to thrombolysis, which he said has not been shown before in a randomized trial.

As the first study to evaluate interventions in an intermediate risk group, Mahfoud suggested this study might be most useful in confirming that the two approaches are probably not interchangeable, and he encourages additional trials of the available therapies across different severities of risk.

In addition, relative costs and optimal timing of interventions are also reasonable variables to assess and compare in future studies of therapies, he said.

Jabar acknowledged the limitations of PEERLESS, but as the first randomized trial for this indication these data provide “important new information to inform endovascular treatment selection.”