TL;DR: 🟡 Positive (soft endpoints) — mechanical thrombectomy beat catheter-directed thrombolysis on a hierarchical composite (win ratio 5.01) for PE, but hard outcomes (mortality, bleeding) were equivalent — benefit is in resource use, not survival.
1. Publication
- Title: Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis in the Management of Intermediate-Risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial
- Acronym: PEERLESS
- Year & Journal: Circulation, published October 28-29, 2024 (2025;151(5):260-273)
- Citation: Jaber WA, Gonsalves CF, Stortecky S, et al. Circulation. 2025;151(5):260-273. doi:10.1161/CIRCULATIONAHA.124.072364
2. Context & Rationale
Background: Both large-bore mechanical thrombectomy (LBMT) and catheter-directed thrombolysis (CDT) have shown positive observational outcomes in intermediate-risk PE, but no prior RCT had directly compared these two interventional strategies.
Research Question/Hypothesis: In intermediate-risk PE patients selected for catheter-based intervention, does LBMT improve a prioritized in-hospital composite outcome and reduce adverse clinical events compared with CDT?
3. Design & Methods
- Study Type: Prospective, international, multicenter, open-label RCT (industry-sponsored, Inari Medical)
- Setting & Centers: 60 international sites
- Population: 550 intermediate-risk PE patients with RV dilatation/dysfunction and additional clinical risk factors
- Intervention: LBMT (Inari FlowTriever system) (n=274)
- Comparator: CDT, at institution/operator discretion (n=276)
- Randomization: 1:1, stratified by VTE-BLEED score (≥2 vs <2)
- Statistical Power & Follow-Up: Primary: hierarchical composite (mortality, ICH, major bleeding, clinical deterioration/bailout, post-procedural ICU utilization/LOS), assessed via win ratio. Follow-up: 24h, discharge, 30 days.
4. Key Results
550 patients randomized.
Outcome | LBMT | CDT | Effect Size | 95% CI | Notes |
Hierarchical composite (primary, win ratio) | Favored | — | Win ratio 5.01 | 3.68–6.97 | Large, significant benefit |
Mortality, ICH, major bleeding | No difference | No difference | — | — | Benefit driven by other composite components |
Clinical deterioration/bailout | Less frequent | More frequent | — | — | Key driver of composite benefit |
ICU admission/length of stay | Lower | Higher | — | — | Key driver of composite benefit |
Hospital stay, 30-day readmission | Shorter, fewer | Longer, more | — | — | Favored LBMT |
5. Internal Validity Assessment
Large, international, multicenter RCT with a prespecified hierarchical win-ratio primary analysis. Overall: Moderate-to-strong — the large win ratio (5.01) is driven primarily by softer, resource-utilization-related endpoints (ICU admission, deterioration/bailout, length of stay) rather than hard endpoints (mortality, ICH, major bleeding), which showed no difference; open-label design and non-standardized CDT arm (mixing ultrasound-facilitated and conventional CDT) are noted limitations by independent reviewers (PCRonline).
6. External Validity Assessment
International, 60-site population selected for catheter-based intervention — relevant to centers with both LBMT and CDT capability; requires the specific decision to intervene to have already been made by the care team.
7. Strengths & Limitations
Strengths: First RCT directly comparing two interventional PE strategies; large sample (550) across many international sites; comprehensive hierarchical outcome capturing multiple clinically relevant domains.
Limitations: Open-label; non-standardized CDT arm (per independent PCRonline critique); industry-sponsored (Inari Medical, device manufacturer); hard endpoints (mortality, ICH, major bleeding) showed no difference — the large win ratio primarily reflects resource-utilization and softer clinical endpoints; 30-day-only follow-up limits long-term inference.
8. Interpretation & Practice Impact
Supports LBMT over CDT for reducing clinical deterioration, ICU utilization, and length of stay in intermediate-risk PE selected for catheter intervention — though this benefit is driven by resource-utilization/deterioration endpoints rather than hard outcomes (mortality, bleeding), an important nuance for interpreting the large win ratio.
9. Controversies & Subsequent Evidence
Independent commentary (tctmd.com) specifically noted that "the win for thrombectomy comes from a difference in length of stay, which also can be influenced by multiple factors" (per Dr. Sista) — an important caution against over-interpreting the headline win-ratio result as reflecting hard-outcome superiority. PEERLESS II (an RCT of LBMT vs anticoagulation alone) is a related, ongoing trial extending this research line.
10. Summary & Executive Takeaway
Summary: PEERLESS, the first RCT directly comparing interventional PE strategies, randomized 550 intermediate-risk PE patients to LBMT or CDT. The hierarchical composite primary outcome strongly favored LBMT (win ratio 5.01, 95% CI 3.68-6.97), driven by less clinical deterioration/bailout and lower ICU utilization/length of stay; hard outcomes (mortality, ICH, major bleeding) showed no difference between strategies.
Overall Takeaway: LBMT reduces clinical deterioration and resource utilization compared with CDT in intermediate-risk PE, representing the most robust head-to-head interventional PE evidence to date — but since hard outcomes (mortality, bleeding) were equivalent, the practical advantage lies specifically in reduced ICU burden and length of stay rather than a demonstrated survival or safety benefit.
11. Bibliography
- Giri J, Mahfoud F, Gebauer B, et al. PEERLESS II: LBMT vs anticoagulation in intermediate-risk PE. J Soc Cardiovasc Angiogr Interv. 2024;3:101982.
- Khandhar S, Jaber W, Bunte MC, et al. FLASH Registry 6-month results. J Soc Cardiovasc Angiogr Interv. 2023;2:101000.