The annual incidence of acute pulmonary embolism (APE) range from 39-115 per 100 000 population. Despite advances in diagnostics, risk stratification and treatment, APE is still the third leading causes of cardiovascular death. Due to high mortality (>20%) and hemodynamic compromise, primary reperfusion therapy is a treatment of choice for patients with high risk APE. However in intermediate high risk APE the mortality rate is also unacceptably high (3-15%) and clinical deterioration occurs in 5-18%. Because of high risk of bleeding complications, including intracranial bleeding (about 2%), in recent years there has been a significant development of interventional techniques for the treatment of patients with APE. Catheter-direct thrombolysis (CTD) and mechanical thrombectomy are the two primary methods used in catheter-based therapy. Observational studies of large-bore mechanical thrombectomy (LBMT) and CDT have separately reported positive outcomes in patients with intermediate-risk PE, but there are no prior randomized controlled trials (RCTs) directly comparing these interventional strategies. Recently, Jaber W. et al. in Circulation, published the PEERLESS study, the first randomized control trial (RCT) to compare LBMT and CTD in the management of intermediate risk APE. Overall, 550 intermediate-risk APE patients, with right ventricular dilatation and additional clinical risk factors, randomized 1:1 to treatment with  LBMT or CDT were included into the study.

The primary endpoint was a hierarchal win ratio (WR) composite of the following: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) postprocedural intensive care unit (ICU) admission and length of stay, assessed at the sooner of hospital discharge or 7 days post-procedure. Assessments at the 24-hour visit included respiratory rate, mMRC dyspnea score, NYHA classification, right ventricle (RV)/left ventricle (LV) ratio reduction, and RV function. Endpoints through 30 days included total hospital stay, all-cause readmission, and all-cause mortality. The primary endpoint occurred significantly less frequently with LBMT vs CDT (WR 5.01 [95% CI: 3.68-6.97]; P<0.001). There were significantly fewer episodes of clinical deterioration and/or bailout (1.8% vs 5.4%; P=0.04) with LBMT vs CDT and less postprocedural ICU utilization (P<0.001), including admissions (41.6% vs 98.6%) and stays >24 hours (19.3% vs 64.5%). There was no significant difference in mortality, intracranial hemorrhage, or major bleeding between strategies. LBMT patients had shorter total hospital stays (4.5±2.8 vs 5.3±3.9 overnights; P=0.002) and fewer all-cause readmissions (3.2% vs 7.9%; P=0.03), while 30-day mortality was similar (0.4% vs 0.8%; P=0.62). There are, of course several limitations of this trial.

• First, this was an open label trial in which patients and investigators were unblinded to treatment.
• Second, treatment in the CDT arm was not standardized, leading to variable device and thrombolytic dose use.
• Third, this trial compared interventional treatment and not heparin as a standard of care.  

Despite this limitations the PEERLESS study provides the first randomized data for mechanical thrombectomy and important new information to inform endovascular treatment selection for intermediate-risk pulmonary embolism patients in whom the decision to intervene has been made by the patient’s care team.

The Authors concluded that compared with CDT, LBMT was associated with significantly fewer clinical deteriorations and/or therapy escalations, less postprocedural ICU utilization, more favorable respiratory rates, symptom scores, and RV function measurements at the 24-hour visit, shorter hospital lengths of stay, and fewer readmissions within 30 days. Although the composition of endpoints, such as the length of intensive care stays—which is inherently longer for CDT patients—has a significant impact on the resulting win ratio, this study shows that both LBMT and CDT are very safe and promising procedures. Prospective studies such as PEERLESS II,  Hi-PEITHO, STORM-PE and PERSEVERE will be instrumental in clarifying the role of catheter-directed treatment compared to standard care, paving the way for advancements in interventional techniques for managing high-risk and intermediate-high-risk APE patients in the years to come. It is to be expected that the widespread use of PERT teams and the development of interventional methods will contribute to reducing the mortality rate of patients with APE.