Dr. Selvi Öztaş

Name of the Study:
Large-bore Mechanical Thrombectomy Versus Catheter-directed Thrombolysis in the Management of Intermediate-risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial

Published in Congress: TCT 2024

Link: 10.1161/CIRCULATIONAHA.124.072364

Objective:

There is a lack of randomized controlled trial (RCT) data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism (PE). The PEERLESS trial is the first RCT to evaluate mechanical thrombectomy and the first to compare two advanced therapies in the management of acute intermediate-risk PE to evaluate differences in acute clinical outcomes. We hypothesized that large-bore mechanical thrombectomy (LBMT) reduces the incidence of in-hospital adverse clinical outcomes compared with catheter-directed thrombolysis (CDT) by providing more rapid removal of emboli and relief of right ventricular (RV) dysfunction.

Methods:
PEERLESS is a prospective, multicenter, RCT that enrolled 550 intermediate-risk PE patients with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with LBMT or CDT. 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.

Results:
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, nor in a secondary WR endpoint including the first 4 components
(WR 1.34 [95% CI: 0.78-2.35]; P=0.30). At the 24-hour visit, respiratory rate was lower for LBMT patients (18.3±3.3 vs. 20.1±5.1; P<0.001) and fewer had moderate to severe mMRC dyspnea scores (13.5% vs. 26.4%; P<0.001), NYHA classifications (16.3% vs. 27.4%; P=0.002), and RV dysfunction (42.1% vs. 57.9%; P=0.004). RV/LV ratio reduction was similar (0.32±0.24 vs. 0.30±0.26; P=0.55). 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).

Conclusion:
PEERLESS met its primary endpoint in favor of LBMT vs. CDT in the treatment of intermediate-risk PE. LBMT had lower rates of clinical deterioration and/or bailout and postprocedural ICU utilization compared with CDT, with no difference in mortality or bleeding.

Comment:
Despite advances in treatment, PE is one of the leading causes of cardiovascular death. While guidelines recommend rapid reperfusion treatments for high-risk PE patients, anticoagulation is preferred in intermediate-risk PE patients due to possible complications. However, clinical deterioration and mortality are high in this patient group, and safe alternative treatments are needed. Although no significant difference was observed in terms of mortality and bleeding in this study, the primary endpoints and significant differences in respiratory rate, mMRC dyspnea score, NYHA classification, RV/LV ratio, and RV function are satisfactory and indicate that LBMT is more effective. These results support its use in many patient groups.