Mechanical Thrombectomy in Pulmonary Embolism: Insights from the PEERLESS Trial

Pulmonary embolism (PE) remains one of the most significant causes of cardiovascular morbidity and mortality, particularly in patients at intermediate risk, who show right ventricular (RV) dysfunction but remain hemodynamically stable. Traditionally, systemic fibrinolysis has been considered for high-risk PE, yet in intermediate-risk cases, the balance between effective clot removal and bleeding risk is challenging. The PEERLESS (Pulmonary Embolism Endovascular Removal of Large Emboli for Severe Symptoms) trial offers critical insights into this area, being the first randomized controlled trial (RCT) to directly compare large-bore mechanical thrombectomy (LBMT) with catheter-directed thrombolysis (CDT) for intermediate-risk PE. By addressing key endpoints related to safety, efficacy, and resource use, PEERLESS represents a breakthrough in guiding clinicians toward safer, more effective interventions for intermediate-risk PE patients.

PEERLESS Trial

Study Design and Methodology: A Unique Approach

PEERLESS was structured as a multicenter, prospective RCT that enrolled 550 patients with intermediate-risk PE who exhibited significant RV dysfunction. Unlike previous studies, the PEERLESS trial used a win-ratio primary endpoint that incorporated multiple adverse outcomes, prioritizing the clinical stability of patients and minimizing ICU utilization. The trial's hierarchy of primary outcomes focused on critical endpoints: all-cause mortality, intracranial hemorrhage (ICH), major bleeding, clinical deterioration, escalation to bailout intervention, and ICU stay. This innovative approach enabled a comprehensive evaluation of each interventional method, making PEERLESS a landmark study in clarifying LBMT's role relative to CDT in PE management.

What is your approach to intermediate- risk pulmonary embolism patients (stable hemodynamics with RV strain)

• 0%Systemic anticoagulation
• 0%Systemic thrombolysis
• 0%Catheter-directed thrombolytic therapy
• 0%Mechanical Thrombectomy

You can vote for more than one answer.

Key Findings: Favoring Large-Bore Mechanical Thrombectomy

The PEERLESS trial highlighted several major benefits of LBMT over CDT. The primary endpoint was achieved in favor of LBMT, with a significant win ratio (5.01; 95% CI: 3.68-6.97; P<0.001), showing that LBMT was associated with fewer adverse outcomes and lower ICU requirements. LBMT patients experienced notably reduced clinical deterioration and fewer escalations to bailout interventions compared to those receiving CDT (1.8% vs. 5.4%; P=0.04). Importantly, LBMT also led to fewer ICU admissions, with only 41.6% of patients requiring ICU care compared to 98.6% of those in the CDT arm. Furthermore, ICU stays exceeding 24 hours were also significantly less common with LBMT (19.3% vs 64.5%; P<0.001), underscoring its potential to relieve ICU burden.

In terms of hospital stay, LBMT resulted in a shorter overall duration (4.5±2.8 vs. 5.3±3.9 days; P=0.002) and reduced 30-day readmission rates (3.2% vs 7.9%; P=0.03). This suggests that LBMT not only enhances immediate clinical stability but may also contribute to long-term recovery, thus reducing the risk of subsequent complications that necessitate readmission. Notably, the rates of mortality, major bleeding, and ICH were comparable between LBMT and CDT (0.4% vs. 0.8% mortality; 6.9% major bleeding in both arms), confirming that LBMT is at least as safe as CDT while offering these additional clinical and resource benefits.

Comparison with Previous Studies: PEITHO and Beyond

PEERLESS builds on the findings of the PEITHO trial, which demonstrated that systemic fibrinolysis in intermediate-risk PE patients could reduce hemodynamic decompensation but at the cost of increased bleeding. In PEITHO, decompensation rates within seven days were reduced from 5.0% with heparin alone to 1.6% with tenecteplase plus heparin. However, the trade-off was a marked increase in major bleeding. PEERLESS, by contrast, suggests that LBMT may reduce deterioration and escalation without increasing the bleeding risk, presenting LBMT as a potentially safer alternative for intermediate-risk PE.

PEERLESS also emphasizes the early clinical stability provided by LBMT. The trial revealed that adverse events for CDT patients tended to occur post-procedurally, averaging 2.1 days after treatment initiation, and included severe incidents such as cardiac arrest and respiratory failure. In contrast, LBMT-related events were managed intra-procedurally and resolved promptly, with no cases of high-grade heart block or cardiac arrest, reflecting LBMT’s favorable risk profile and faster stabilization.

Early Recovery Benefits: Insights from the 24-Hour Visit

PEERLESS also provides critical data on LBMT’s advantages during the early recovery phase. At the 24-hour mark, LBMT patients exhibited better Modified Medical Research Council (mMRC) dyspnea scores, improved New York Heart Association (NYHA) classifications, and enhanced RV function on echocardiography compared to CDT patients. These benefits reflect LBMT’s ability for effective thrombus removal, likely contributing to faster right heart recovery, symptomatic relief, and prevention of further deterioration. LBMT patients also showed significantly lower respiratory rates and modified Borg dyspnea scores, indicating a quicker return to respiratory stability and comfort. These early recovery indicators highlight LBMT’s superior immediate efficacy compared to CDT, further positioning it as a promising treatment for intermediate-risk PE.

Study Limitations and Future Directions

While PEERLESS offers significant insights, certain limitations must be acknowledged. The open-label design may introduce potential bias as treatment allocation was visible to both patients and investigators. Furthermore, the lack of a standardized protocol for CDT could introduce variability, as different devices and thrombolytic dosages were used across sites. This variability, while reflecting real-world practice, complicates direct comparisons. Additionally, PEERLESS did not include a standard anticoagulation control group, a limitation that other studies like PEERLESS II and HI-PEITHO aim to address. Finally, the 30-day follow-up period restricts insights into long-term outcomes, and while readmission rates favored LBMT, more extended follow-up is necessary to understand the durability of these benefits.

Conclusion: Redefining PE Management with LBMT

The PEERLESS trial provides compelling evidence that LBMT offers an effective and safe alternative to CDT for intermediate-risk PE patients, with benefits in ICU utilization, lower clinical deterioration rates, and shorter hospital stays. These advantages make LBMT a resource-efficient option, especially valuable in high-demand healthcare environments. By providing improved early recovery outcomes and a lower risk of delayed complications, LBMT is well-positioned as a front-line interventional strategy for PE patients with RV dysfunction.

Looking forward, ongoing RCTs like PEERLESS II, PE_TRACT and HI-PEITHO are expected to further validate LBMT’s role and expand its clinical application. PEERLESS marks a critical step toward optimizing PE care, setting the stage for broader adoption of LBMT and a new standard of care in managing intermediate-risk pulmonary embolism.

REFERENCES

1. Jaber WA, Gonsalves CF, Stortecky S, et al., for the PEERLESS Committees and Investigators. Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis in the Management of Intermediate-Risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial. Circulation 2024;Oct 29:[Epub ahead of print].

2. Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370:1402-1411. doi: 10.1056/NEJMoa1302097.