Randomized Controlled Trial

. 2025 Feb 4;151(5):260-273.

doi: 10.1161/CIRCULATIONAHA.124.072364. Epub 2024 Oct 29.

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis in the Management of Intermediate-Risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial

Wissam A Jaber¹, Carin F Gonsalves², Stefan Stortecky³, Samuel Horr⁴, Orestis Pappas⁵, Ripal T Gandhi⁶, Keith Pereira⁷, Jay Giri⁸, Sameer J Khandhar⁹, Khawaja Afzal Ammar¹⁰, David M Lasorda¹¹, Brian Stegman¹², Lucas Busch¹³, David J Dexter 2nd¹⁴, Ezana M Azene¹⁵, Nikhil Daga¹⁶, Fakhir Elmasri¹⁷, Chandra R Kunavarapu¹⁸, Mark E Rea¹⁹, Joseph S Rossi²⁰, Joseph Campbell²¹, Jonathan Lindquist²², Adam Raskin²³, Jason C Smith²⁴, Thomas M Tamlyn²⁵, Gabriel A Hernandez²⁶, Parth Rali²⁷, Torrey R Schmidt²⁸, Jeffrey T Bruckel²⁹, Juan C Camacho³⁰, Jun Li³¹, Samy Selim³², Catalin Toma³³, Sukhdeep Singh Basra³⁴, Brian A Bergmark³⁵, Bhavraj Khalsa³⁶, David M Zlotnick³⁷, Jordan Castle³⁸, David J O'Connor³⁹, C Michael Gibson⁴⁰; PEERLESS Committees and Investigators*

Affiliations

¹ Emory University Hospital, Atlanta, GA (W.A.J.).
² Thomas Jefferson University Hospitals, Philadelphia, PA (C.F.G.).
³ Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Switzerland (S. Stortecky).
⁴ Centennial Medical Center, Nashville, TN (S.H.).
⁵ Allegheny Health Network, Erie, PA (O.P.).
⁶ Miami Cardiac and Vascular Institute, Baptist Health South Florida (R.T.G.).
⁷ Saint Louis University, MO (K.P.).
⁸ Cardiovascular Medicine Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia (J.G.).
⁹ Perelman School of Medicine, University of Pennsylvania, Philadelphia (S.J.K.).
¹⁰ Advocate Aurora St. Luke's Medical Center, Milwaukee, WI (K.A.A.).
¹¹ Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA (D.M.L.).
¹² CentraCare Heart and Vascular Center, St. Cloud, MN (B.S.).
¹³ Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Germany (L.B.).
¹⁴ Sentara Healthcare, Macon & Joan Brock Virginia Health Sciences, Old Dominion University, Norfolk, VA (D.J.D.).
¹⁵ Emplify Health, La Crosse, WI (E.M.A.).
¹⁶ Huntington Hospital, Pasadena, CA (N.D.).
¹⁷ Lakeland Vascular Institute, FL (F.E.).
¹⁸ Methodist Heart and Lung Institute, San Antonio, TX (C.R.K.).
¹⁹ Summa Health System, Akron, OH (M.E.R.).
²⁰ University of North Carolina, Chapel Hill (J.S.R.).
²¹ OhioHealth Riverside Methodist Hospital, Columbus (J.Campbell).
²² University of Colorado Anschutz Medical Campus, Aurora (J. Lindquist).
²³ Mercy Heart Institute, Cincinnati, OH (A.R.).
²⁴ Loma Linda University Health, CA (J.C.S.).
²⁵ Heart and Vascular Institute of Wisconsin, Ascension St. Elizabeth Hospital, Appleton (T.M.T.).
²⁶ University of Mississippi Medical Center, Jackson (G.A.H.).
²⁷ Temple University Hospital, Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Philadelphia, PA (P.R.).
²⁸ University of Pittsburgh Medical Center, Harrisburg, PA (T.R.S.).
²⁹ University of Rochester Medical Center, NY (J.T.B.).
³⁰ Department of Clinical Sciences, Florida State University, Sarasota (J.C.C.).
³¹ University Hospitals Harrington Heart and Vascular Institute, Parma, OH (J. Li).
³² Northwell Health, Manhasset, NY (S. Selim; now at St. Francis Hospital and Heart Center, Roslyn, NY).
³³ University of Pittsburgh Medical Center, PA (C.T.).
³⁴ University of Texas Health Science Center at Houston (S.S.B.).
³⁵ TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (B.A.B.).
³⁶ Providence St. Joseph Heart and Vascular Center, Orange, CA (B.K.).
³⁷ University at Buffalo, NY (D.M.Z.).
³⁸ Inland Imaging, Spokane, WA (J.Castle).
³⁹ Hackensack University Medical Center, NJ (D.J.O.).
⁴⁰ Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G.).

PMID: 39470698
PMCID: PMC11789609
DOI: 10.1161/CIRCULATIONAHA.124.072364

Randomized Controlled Trial

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis in the Management of Intermediate-Risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial

Wissam A Jaber et al. Circulation. 2025.

. 2025 Feb 4;151(5):260-273.

doi: 10.1161/CIRCULATIONAHA.124.072364. Epub 2024 Oct 29.

Authors

Affiliations

¹ Emory University Hospital, Atlanta, GA (W.A.J.).
² Thomas Jefferson University Hospitals, Philadelphia, PA (C.F.G.).
³ Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Switzerland (S. Stortecky).
⁴ Centennial Medical Center, Nashville, TN (S.H.).
⁵ Allegheny Health Network, Erie, PA (O.P.).
⁶ Miami Cardiac and Vascular Institute, Baptist Health South Florida (R.T.G.).
⁷ Saint Louis University, MO (K.P.).
⁸ Cardiovascular Medicine Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia (J.G.).
⁹ Perelman School of Medicine, University of Pennsylvania, Philadelphia (S.J.K.).
¹⁰ Advocate Aurora St. Luke's Medical Center, Milwaukee, WI (K.A.A.).
¹¹ Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA (D.M.L.).
¹² CentraCare Heart and Vascular Center, St. Cloud, MN (B.S.).
¹³ Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Germany (L.B.).
¹⁴ Sentara Healthcare, Macon & Joan Brock Virginia Health Sciences, Old Dominion University, Norfolk, VA (D.J.D.).
¹⁵ Emplify Health, La Crosse, WI (E.M.A.).
¹⁶ Huntington Hospital, Pasadena, CA (N.D.).
¹⁷ Lakeland Vascular Institute, FL (F.E.).
¹⁸ Methodist Heart and Lung Institute, San Antonio, TX (C.R.K.).
¹⁹ Summa Health System, Akron, OH (M.E.R.).
²⁰ University of North Carolina, Chapel Hill (J.S.R.).
²¹ OhioHealth Riverside Methodist Hospital, Columbus (J.Campbell).
²² University of Colorado Anschutz Medical Campus, Aurora (J. Lindquist).
²³ Mercy Heart Institute, Cincinnati, OH (A.R.).
²⁴ Loma Linda University Health, CA (J.C.S.).
²⁵ Heart and Vascular Institute of Wisconsin, Ascension St. Elizabeth Hospital, Appleton (T.M.T.).
²⁶ University of Mississippi Medical Center, Jackson (G.A.H.).
²⁷ Temple University Hospital, Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Philadelphia, PA (P.R.).
²⁸ University of Pittsburgh Medical Center, Harrisburg, PA (T.R.S.).
²⁹ University of Rochester Medical Center, NY (J.T.B.).
³⁰ Department of Clinical Sciences, Florida State University, Sarasota (J.C.C.).
³¹ University Hospitals Harrington Heart and Vascular Institute, Parma, OH (J. Li).
³² Northwell Health, Manhasset, NY (S. Selim; now at St. Francis Hospital and Heart Center, Roslyn, NY).
³³ University of Pittsburgh Medical Center, PA (C.T.).
³⁴ University of Texas Health Science Center at Houston (S.S.B.).
³⁵ TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (B.A.B.).
³⁶ Providence St. Joseph Heart and Vascular Center, Orange, CA (B.K.).
³⁷ University at Buffalo, NY (D.M.Z.).
³⁸ Inland Imaging, Spokane, WA (J.Castle).
³⁹ Hackensack University Medical Center, NJ (D.J.O.).
⁴⁰ Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G.).

PMID: 39470698
PMCID: PMC11789609
DOI: 10.1161/CIRCULATIONAHA.124.072364

Abstract

Background: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

Methods: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to bailout, and (5) postprocedural intensive care unit admission and length of stay. Assessments at the 24-hour visit included respiratory rate, modified Medical Research Council dyspnea score, New York Heart Association classification, right ventricle/left ventricle ratio reduction, and right ventricular function. End points through 30 days included total hospital stay, all-cause readmission, and all-cause mortality.

Results: The primary end point occurred significantly less frequently with LBMT compared with CDT (win ratio, 5.01 [95% CI, 3.68-6.97]; P<0.001). There were significantly fewer episodes of clinical deterioration and/or bailout (1.8% versus 5.4%; P=0.04) with LBMT compared with CDT and less postprocedural intensive care unit use (P<0.001), including admissions (41.6% versus 98.6%) and stays >24 hours (19.3% versus 64.5%). There were no significant differences in mortality, intracranial hemorrhage, or major bleeding between strategies or in a secondary win ratio end point including the first 4 components (win ratio, 1.34 [95% CI, 0.78-2.35]; P=0.30). At the 24-hour visit, respiratory rate was lower for patients treated with LBMT (18.3±3.3 versus 20.1±5.1; P<0.001), and fewer had moderate to severe modified Medical Research Council dyspnea scores (13.5% versus 26.4%; P<0.001), New York Heart Association classifications (16.3% versus 27.4%; P=0.002), and right ventricular dysfunction (42.1% versus 57.9%; P=0.004). Right ventricle/left ventricle ratio reduction was similar (0.32±0.24 versus 0.30±0.26; P=0.55). Patients treated with LBMT had shorter total hospital stays (4.5±2.8 overnights versus 5.3±3.9 overnights; P=0.002) and fewer all-cause readmissions (3.2% versus 7.9%; P=0.03), whereas 30-day mortality was similar (0.4% versus 0.8%; P=0.62).

Conclusions: PEERLESS met its primary end point in favor of LBMT compared with CDT in treatment of intermediate-risk pulmonary embolism. LBMT had lower rates of clinical deterioration and/or bailout and postprocedural intensive care unit use compared with CDT, with no difference in mortality or bleeding.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05111613.

Keywords: percutaneous aspiration; pulmonary embolism; randomized controlled trial; thrombectomy; thrombolytic therapy.

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Conflict of interest statement

Dr Jaber reports research grant/funding from Inari Medical, Medtronic, and Thrombolex; consultant fees from Abbott, Inari Medical, and Medtronic; and advisory board membership with Thrombolex. Dr Gonsalves reports research grant/funding from Inari Medical and consultant fees from Inari Medical. Dr Stortecky reports institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic, as well as consultant fees from Inari Medical. Dr Horr reports consultant fees from Argon, BD, Boston Scientific, Cook, Cordis, Inari Medical, Medtronic, and Penumbra. Dr Pappas reports research grant/funding from Inari Medical and consultant fees from Abiomed, Boston Scientific, Inari Medical, Medtronic, and Zoll. Dr Gandhi reports consultant fees from Argon, BD, Boston Scientific, Cook, Cordis, Inari Medical, Medtronic, and Penumbra. Dr Giri reports research grant/funding from Edwards Lifesciences and Inari Medical; consultant fees from Boston Scientific and Inari Medical; honoraria from Edwards Lifesciences; equity ownership in Endovascular Engineering; and advisory board membership with Boston Scientific. Dr Khandhar reports consultant fees from Inari Medical and Neptune Medical. Dr Lasorda reports consultant fees from Cardiovascular Systems Inc, Edwards Lifesciences, and Shockwave Medical. Dr Dexter reports consultant fees from AngioDynamics, Boston Scientific, Inari Medical, and Penumbra. Dr Azene reports research grant/funding from Endovascular Engineering and Inari Medical; consultant fees from Medtronic and Philips; and honoraria from Philips. Dr Campbell reports consultant fees from Inari Medical. Dr Lindquist reports research grant/funding from Adient Medical, AstraZeneca, GE, Inari Medical, Philips, and Sirtex; consultant fees from Boston Scientific, EndoShape Inc, Inari Medical, Philips, and TriSalus Life Sciences; honoraria from Boston Scientific and Inari Medical; and advisory board membership with Boston Scientific, Inari Medical, and TriSalus Life Sciences. Dr Raskin reports consultant fees from Abbott Medical, Abiomed, Imperative Care, and Inari Medical. Dr Hernandez reports advisory board membership with Philips. Dr Rali reports research grant/funding from Janssen, ThinkSono, Thrombolex, and Viz.AI; consultant fees from AIDOC, Inari Medical, Penumbra, ThinkSono, Thrombolex, and Viz.AI; honoraria from Janssen; and advisory board membership with Inari Medical and Thrombolex. Dr Bruckel reports research grants/funding from Inari Medical; consultant fees from Asahi Intecc Medical; and honoraria from Medtronic. Dr Camacho reports research grants/funding from Elestra and TriSalus Life Sciences; consultant fees from Pulse Biosciences and TriSalus Life Sciences; honoraria from Wolters Kluwer (SIO, CIO). Dr Toma reports consultant fees from Neptune Medical. Dr Basra reports consultant fees from Abbott, AngioDynamics, and Lexicon. Dr Bergmark reports research grants/funding from Abbott Vascular, Amgen, AstraZeneca, Inari Medical, Ionis, Pfizer, and Philips, as well as advisory board membership with Boston Scientific. Dr O’Connor reports research grants/funding from Abbott, Boston Scientific, and Silk Road and consultant fees from Philips. Dr Gibson reports consultant support to spouse from Inari Medical. The other authors report no conflicts.

Figures

**Figure 1.**
**Win ratio end points and odds ratios for the win ratio components.** Shown are the primary and secondary win ratio end points (A) and the odds ratios for the clinical outcome components of the win ratios (B), assessed at the sooner of discharge or 7 days after the procedure. P values for the win ratio end points are derived with a modified generalized Wilcoxon test (F-S test), and P values for clinical outcomes of the win ratio are derived from the 2-sided Fisher exact test. Odds ratios and 95% Wald CIs are calculated with large-bore mechanical thrombectomy (LBMT) as the reference. *N=275 because of 1 death. CDT indicates catheter-directed thrombolysis; and ICU, intensive care unit.

**Figure 2.**
**Functional and imaging assessments at the 24-hour visit.** Assessments at the 24-hour visit included the proportion of patients with a modified Medical Research Council (mMRC) dyspnea score <3 vs ≥3 (A), mean respiratory rate (B), proportion of patients New York Heart Association (NYHA) class I or II vs class III or IV (C), mean modified Borg dyspnea score at rest (D), proportion of patients with normal or mildly reduced vs moderately or severely reduced right ventricular (RV) function among those with echocardiograms at baseline and 24-hour visit (E), and mean reduction in RV/left ventricle (LV) ratio from baseline based on the same type of imaging (echocardiogram or computed tomography pulmonary angiogram) at baseline and 24-hour visit (F). P values are derived from the 2-sided Fisher exact test for categorical variables (mMRC score, NYHA classification, and RV function) and from Wilcoxon rank-sum tests with continuity correction for continuous variables (respiratory rate, modified Borg score, and reduction in RV/LV ratio). CDT indicates catheter-directed thrombolysis; and LBMT, large-bore mechanical thrombectomy.

**Figure 3.**
**ICU use and length of stays.** Shown is postprocedural intensive care unit (ICU) use (proportion of patients with no ICU admission, ICU admission lasting 0–24 hours, and ICU admission lasting >24 hours; A) and the mean postprocedural ICU length of stay in hours among all patients (B). ICU length of stay is measured from the end of the index procedure or the time of ICU admission, whichever is later, until the time of an order to discharge from the ICU or transfer to a standard or lower-acuity unit. Total hospital length of stay is reported by number of overnights (C); postprocedural hospital length of stay is reported in days (D). P values are derived from the 2-sided Fisher exact test for categorical variables (postprocedural ICU admission) and from Wilcoxon rank-sum tests with continuity correction for continuous variables (postprocedural ICU, postprocedural hospital, and total hospital lengths of stay). CDT indicates catheter-directed thrombolysis; and LBMT, large-bore mechanical thrombectomy.

See this image and copyright information in PMC

Comment in

A Win for Clinical Evidence: The First Head-to-Head Trial of Interventional Strategies for the Treatment of Pulmonary Embolism.
Rao SV, Gutierrez JAT. Rao SV, et al. Circulation. 2025 Feb 4;151(5):274-276. doi: 10.1161/CIRCULATIONAHA.124.072972. Epub 2025 Feb 3. Circulation. 2025. PMID: 39899637 No abstract available.

References

1. Gotzinger F, Lauder L, Sharp ASP, Lang IM, Rosenkranz S, Konstantinides S, Edelman ER, Bohm M, Jaber W, Mahfoud F. Interventional therapies for pulmonary embolism. Nat Rev Cardiol. 2023;20:670–684. doi: 10.1038/s41569-023-00876-0 - PMC - PubMed
1. Martin KA, Molsberry R, Cuttica MJ, Desai KR, Schimmel DR, Khan SS. Time trends in pulmonary embolism mortality rates in the United States, 1999 to 2018. J Am Heart Assoc. 2020;9:e016784. doi: 10.1161/JAHA.120.016784 - PMC - PubMed
1. Wendelboe AM, Raskob GE. Global burden of thrombosis: epidemiologic aspects. Circ Res. 2016;118:1340–1347. doi: 10.1161/CIRCRESAHA.115.306841 - PubMed
1. Zghouzi M, Mwansa H, Shore S, Hyder SN, Kamdar N, Moles VM, Barnes GD, Froehlich J, McLaughlin VV, Paul TK, et al. . Sex, racial, and geographic disparities in pulmonary embolism-related mortality nationwide. Ann Am Thorac Soc. 2023;20:1571–1577. doi: 10.1513/AnnalsATS.202302-091OC - PubMed
1. Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jimenez D, et al. ; ESC Scientific Document Group. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41:543–603. doi: 10.1093/eurheartj/ehz405 - PubMed

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Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis in the Management of Intermediate-Risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial

Affiliations

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis in the Management of Intermediate-Risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial

Authors

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Conflict of interest statement

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