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. 2022 Aug 8;8(8):CD013083.
doi: 10.1002/14651858.CD013083.pub2.

Catheter-directed therapies for the treatment of high risk (massive) and intermediate risk (submassive) acute pulmonary embolism

John J Harvey  1   2 , Shiwei Huang  3 , Raman Uberoi  4
Affiliations

Catheter-directed therapies for the treatment of high risk (massive) and intermediate risk (submassive) acute pulmonary embolism

John J Harvey et al. Cochrane Database Syst Rev. .

Abstract

Background: Acute pulmonary embolism (APE) is a major cause of acute morbidity and mortality. APE results in long-term morbidity in up to 50% of survivors, known as post-pulmonary embolism (post-PE) syndrome. APE can be classified according to the short-term (30-day) risk of mortality, based on a variety of clinical, imaging and laboratory findings. Most mortality and morbidity is concentrated in high-risk (massive) and intermediate-risk (submassive) APE. The first-line treatment for APE is systemic anticoagulation. High-risk (massive) APE accounts for less than 10% of APE cases and is a life-threatening medical emergency, requiring immediate reperfusion treatment to prevent death. Systemic thrombolysis is the recommended treatment for high-risk (massive) APE. However, only a minority of the people affected receive systemic thrombolysis, due to comorbidities or the 10% risk of major haemorrhagic side effects. Of those who do receive systemic thrombolysis, 8% do not respond in a timely manner. Surgical pulmonary embolectomy is an alternative reperfusion treatment, but is not widely available. Intermediate-risk (submassive) APE represents 45% to 65% of APE cases, with a short-term mortality rate of around 3%. Systemic thrombolysis is not recommended for this group, as major haemorrhagic complications outweigh the benefit. However, the people at higher risk within this group have a short-term mortality of around 12%, suggesting that anticoagulation alone is not an adequate treatment. Identification and more aggressive treatment of people at intermediate to high risk, who have a more favourable risk profile for reperfusion treatments, could reduce short-term mortality and potentially reduce post-PE syndrome. Catheter-directed treatments (catheter-directed thrombolysis and catheter embolectomy) are minimally invasive reperfusion treatments for high- and intermediate-risk APE. Catheter-directed treatments can be used either as the primary treatment or as salvage treatment after failure of systemic thrombolysis. Catheter-directed thrombolysis administers 10% to 20% of the systemic thrombolysis dose directly into the thrombus in the lungs, potentially reducing the risks of haemorrhagic side effects. Catheter embolectomy mechanically removes the thrombus without the need for thrombolysis, and may be useful for people with contraindications for thrombolysis. Currently, the benefits of catheter-based APE treatments compared with existing medical and surgical treatment are unclear despite increasing adoption of catheter treatments by PE response teams. This review examines the evidence for the use of catheter-directed treatments in high- and intermediate-risk APE. This evidence could help guide the optimal treatment strategy for people affected by this common and life-threatening condition.

Objectives: To assess the effects of catheter-directed therapies versus alternative treatments for high-risk (massive) and intermediate-risk (submassive) APE.

Search methods: We used standard, extensive Cochrane search methods. The latest search was 15 March 2022.

Selection criteria: We included randomised controlled trials (RCTs) of catheter-directed therapies for the treatment of high-risk (massive) and intermediate-risk (submassive) APE. We excluded catheter-directed treatments for non-PE. We applied no restrictions on participant age or on the date, language or publication status of RCTs.

Data collection and analysis: We used standard Cochrane methods. The main outcomes were all-cause mortality, treatment-associated major and minor haemorrhage rates based on two established clinical definitions, recurrent APE requiring retreatment or change to a different APE treatment, length of hospital stay, and quality of life. We used GRADE to assess certainty of evidence for each outcome.

Main results: We identified one RCT (59 participants) of (ultrasound-augmented) catheter-directed thrombolysis for intermediate-risk (submassive) APE. We found no trials of any catheter-directed treatments (thrombectomy or thrombolysis) in people with high-risk (massive) APE or of catheter-based embolectomy in people with intermediate-risk (submassive) APE. The included trial compared ultrasound-augmented catheter-directed thrombolysis with alteplase and systemic heparinisation versus systemic heparinisation alone. In the treatment group, each participant received an infusion of alteplase 10 mg or 20 mg over 15 hours. We identified a high risk of selection and performance bias, low risk of detection and reporting bias, and unclear risk of attrition and other bias. Certainty of evidence was very low because of risk of bias and imprecision. By 90 days, there was no clear difference in all-cause mortality between the treatment group and control group. A single death occurred in the control group at 20 days after randomisation, but it was unrelated to the treatment or to APE (odds ratio (OR) 0.31, 95% confidence interval (CI) 0.01 to 7.96; 59 participants). By 90 days, there were no episodes of treatment-associated major haemorrhage in either the treatment or control group. There was no clear difference in treatment-associated minor haemorrhage between the treatment and control group by 90 days (OR 3.11, 95% CI 0.30 to 31.79; 59 participants). By 90 days, there were no episodes of recurrent APE requiring retreatment or change to a different APE treatment in the treatment or control group. There was no clear difference in the length of mean total hospital stay between the treatment and control groups. Mean stay was 8.9 (standard deviation (SD) 3.4) days in the treatment group versus 8.6 (SD 3.9) days in the control group (mean difference 0.30, 95% CI -1.57 to 2.17; 59 participants). The included trial did not investigate quality of life measures. AUTHORS' CONCLUSIONS: There is a lack of evidence to support widespread adoption of catheter-based interventional therapies for APE. We identified one small trial showing no clear differences between ultrasound-augmented catheter-directed thrombolysis with alteplase plus systemic heparinisation versus systemic heparinisation alone in all-cause mortality, major and minor haemorrhage rates, recurrent APE and length of hospital stay. Quality of life was not assessed. Multiple small retrospective case series, prospective patient registries and single-arm studies suggest potential benefits of catheter-based treatments, but they provide insufficient evidence to recommend this approach over other evidence-based treatments. Researchers should consider clinically relevant primary outcomes (e.g. mortality and exercise tolerance), rather than surrogate markers (e.g. right ventricular to left ventricular (RV:LV) ratio or thrombus burden), which have limited clinical utility. Trials must include a control group to determine if the effects are specific to the treatment.

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Conflict of interest statement

JJH: none SH: none RU: none

Figures

1
1
Study PRISMA flow diagram.
RCT: randomised controlled trial
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages in the included trial.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item in the included trial.
1.1
1.1. Analysis
Comparison 1: Ultrasound‐assisted catheter‐directed thrombolysis (USAT) + unfractionated heparin (UFH) versus UFH, Outcome 1: All‐cause mortality (90 days)
1.2
1.2. Analysis
Comparison 1: Ultrasound‐assisted catheter‐directed thrombolysis (USAT) + unfractionated heparin (UFH) versus UFH, Outcome 2: Difference in RV:LV ratio from baseline
1.3
1.3. Analysis
Comparison 1: Ultrasound‐assisted catheter‐directed thrombolysis (USAT) + unfractionated heparin (UFH) versus UFH, Outcome 3: Major haemorrhage
1.4
1.4. Analysis
Comparison 1: Ultrasound‐assisted catheter‐directed thrombolysis (USAT) + unfractionated heparin (UFH) versus UFH, Outcome 4: Minor haemorrhage
1.5
1.5. Analysis
Comparison 1: Ultrasound‐assisted catheter‐directed thrombolysis (USAT) + unfractionated heparin (UFH) versus UFH, Outcome 5: Recurrence of APE
1.6
1.6. Analysis
Comparison 1: Ultrasound‐assisted catheter‐directed thrombolysis (USAT) + unfractionated heparin (UFH) versus UFH, Outcome 6: Length of hospital stay [days]
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD013083

References

References to studies included in this review

Kucher 2014 {published data only}
    1. Kucher N, Boekstegers P, Muller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014;129(4):479-86. [DOI: 10.1161/CIRCULATIONAHA.113.005544] - DOI - PubMed

References to studies excluded from this review

Avgerinos 2018 {published data only}
    1. Avgerinos ED, Mohapatra A, Rivera-Lebron B, Toma, C, Kabrhel C, Fish L, et al. Design and rationale of a randomized trial comparing standard versus ultrasound-assisted thrombolysis for submassive pulmonary embolism. Journal of Vascular Surgery 2018;6(1):126-32. [DOI: 10.1016/j.jvsv.2017.09.004] - DOI - PMC - PubMed
Edla 2016 {published data only}
    1. Edla S, Boshara A, Neupane S, Mehta RH, Rosman H, Attallah A. Safety and efficacy of ultrasound-assisted catheter-directed thrombolysis in treatment of submassive pulmonary embolism. Circulation 2016;134(Suppl 1):A19993.
FLARE 2019 {published data only}
    1. Tu T, Toma C, Tapson VF, Adams C, Jaber WA, Silver M, et al. A prospective, single-arm, multicenter trial of catheter-directed mechanical thrombectomy for intermediate-risk acute pulmonary embolism: the FLARE study. JACC: Cardiovascular Interventions 2019;12(9):859-69. [DOI: 10.1016/j.jcin.2018.12.022] - DOI - PubMed
Jaber 2020 {published data only}
    1. Jaber WA, Kabrhel C, Rosenfield K, Tu T, Ouriel K, Tapson VF. Percutaneous thrombectomy in emergency department patients with pulmonary embolism: the FLARE ED sub-study. Journal of Emergency Medicine 2020;58(2):175-82. [DOI: 10.1016/j.jemermed.2019.11.044] - DOI - PubMed
NCT03086317 {published data only}
    1. NCT03086317. Standard vs ultrasound-assisted catheter thrombolysis for submassive pulmonary embolism. clinicaltrials.gov/show/NCT03086317 (first received 22 March 2017).
NCT03218410 {published data only}
    1. NCT03218410. Surgical pulmonary embolectomy versus catheter-directed thrombolysis in the treatment of pulmonary embolism: a non-inferiority study (Lungembolism). clinicaltrials.gov/ct2/show/NCT03218410 (first received 14 July 2017).
NCT04430569 {published data only}
    1. NCT04430569. Pulmonary Embolism International THrOmbolysis Study-3 (PEITHO-3). clinicaltrials.gov/ct2/show/NCT04430569 (first received 12 June 2020).
NCT05111613 {published data only}
    1. NCT05111613. The PEERLESS Study (PEERLESS). clinicaltrials.gov/ct2/show/NCT05111613 (first received 8 November 2021). [CLINICALTRIALS.GOV IDENTIFIER: NCT05111613]
OPTALYSE‐PE 2018 {published data only}
    1. Sterling K, Jones N, Piazza G, Goldhaber S, Tapson V. Optimum duration and dose of rTPA with the acoustic pulse thrombolysisis procedure for intermediate-risk (submassive) pulmonary embolism: OPTALYSE PE. Journal of Vascular and Interventional Radiology 2018;29(4 Suppl 1):S96.
    1. Sterling KM, Jones N, Piazza G, Goldhaber S, Tapson V. Optimum duration and dose of r-TPA with the acoustic pulse thrombolysis procedure for intermediate-risk (submassive) pulmonary embolism (OPTALYSE PE). Cardiovascular and Interventional Radiology 2017;40(2 Suppl 1):S142. [DOI: 10.1007/s00270-017-1725-y] - DOI
    1. Tapson VF, Piazza G, Goldhaber SZ, Sterling K, Ouriel K, Liu PY. Optimum duration and dose of r-tpa with the acoustic pulse thrombolysis procedure for intermediate-risk (submassive) pulmonary embolism: OPTALYSE-PE. American Journal of Respiratory and Critical Care Medicine 2017;195:A2835. [DOI: 10.1164/ajrccm-conference.2017.A108] - DOI
    1. Tapson VF, Sterling K, Jones N, Elder M, Tripathy U, Brower J, et al. A randomized trial of the optimum duration of acoustic pulse thrombolysis procedure in acute intermediate-risk pulmonary embolism: the OPTALYSE PE trial. JACC: Cardiovascular Interventions 2018;11(14):1401-10. [DOI: 10.1016/j.jcin.2018.04.008] - DOI - PubMed

References to ongoing studies

NCT03854266 {published data only}
    1. NCT03854266. Low dose catheter directed thrombolysis for acute pulmonary embolism (BETULA). clinicaltrials.gov/ct2/show/NCT03854266 (first received 26 February 2019).
NCT04088292 {unpublished data only}
    1. NCT04088292. Low dose thrombolysis, ultrasound assisted thrombolysis or heparin for intermediate high risk pulmonary embolism (STRATIFY). clinicaltrials.gov/ct2/show/NCT04088292 (first received 12 September 2019). [CLINICALTRIALS.GOV ID: NCT04088292]
NCT04790370 {published data only}
    1. NCT04790370. Ultrasound-facilitated, catheter-directed thrombolysis in intermediate-high risk pulmonary embolism (HI-PEITHO). clinicaltrials.gov/ct2/show/NCT04790370 (first received 3 November 2021).

Additional references

ACCP 2016
    1. Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016;149(2):315-52. [DOI: 10.1016/j.chest.2015.11.026] - DOI - PubMed
ACCP 2021
    1. Stevens SM, Woller SC, Baumann Kreuziger L, Bounameaux H, Doerschug K, Geersing GJ, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report – executive summary. Chest 2021;160(6):e545-608. [DOI: 10.1016/j.chest.2021.07.056] - DOI - PubMed
AHA 2011
    1. Jaff MR, McMurty MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011;123(16):1788-830. [DOI: 10.1161/CIR.0b013e318214914f] - DOI - PubMed
AHA 2019
    1. Giri J, Sista AK, Weinberg I, Kearon C, Kumbhani DJ, Desai ND, et al. Interventional therapies for acute pulmonary embolism: current status and principles for the development of novel evidence: a scientific statement from the American Heart Association. Circulation 2019;140(20):e774-e801. [DOI: 10.1161/CIR.0000000000000707] - DOI - PubMed
Alkinj 2017
    1. Alkinj B, Pannu BS, Apala DR, Kotecha A, Kashyap R, Iyer VN. Saddle vs nonsaddle pulmonary embolism: clinical presentation, hemodynamics, management, and outcomes. Mayo Clinic Proceedings 2017;92(10):1511-8. [DOI: 10.1016/j.mayocp.2017.07.014] - DOI - PubMed
ASH 2020
    1. Ortel TL, Neumann I, Ageno W, Beyth R, Clark NP, Cuker A, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Advances 2020;4(19):4693-738. [DOI: 10.1182/bloodadvances.2020001830] - DOI - PMC - PubMed
Atkins 2004
    1. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ 2004;328(7454):1490-4. - PMC - PubMed
ATTRACT 2017
    1. Vedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, et al, on behalf of the ATTRACT Trial Investigators. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. New England Journal of Medicine 2017;377(23):2240-52. [DOI: 10.1056/NEJMoa1615066] - DOI - PMC - PubMed
Barco 2021
    1. Barco S, Valerio L, Gallo A, Turatti G, Mahmoudpour SH, Ageno W, et al. Global reporting of pulmonary embolism-related deaths in the World Health Organization mortality database: vital registration data from 123 countries. Research and Practice in Thrombosis and Haemostasis 2021;5(5):e12520. [DOI: 10.1002/rth2.12520] - DOI - PMC - PubMed
Barnes 2020
    1. Barnes GD, Muzikansky A, Cameron S, Giri J, Heresi GA, Jaber W, et al. Comparison of 4 acute pulmonary embolism mortality risk scores in patients evaluated by pulmonary embolism response teams. JAMA Network Open 2020;3(8):e2010779. [DOI: 10.1001/jamanetworkopen.2020.10779] - DOI - PMC - PubMed
Becattini 2016
    1. Becattini C, Agnelli G, Lankeit M, Masotti L, Pruszczyk P, Casazza F, et al. Acute pulmonary embolism: mortality prediction by the 2014 European Society of Cardiology risk stratification model. European Respiratory Journal 2016;48(3):780-6. [DOI: 10.1183/13993003.00024-2016] - DOI - PubMed
Beyer 2020
    1. Beyer SE, Shanafelt C, Pinto DS, Weinstein JL, Aronow HD, Weinberg I, et al. Utilization and outcomes of thrombolytic therapy for acute pulmonary embolism: a nationwide cohort study. Chest 2020;157(3):645-53. [DOI: 10.1016/j.chest.2019.10.049] - DOI - PubMed
Bloomer 2017
    1. Bloomer TL, El-Hayek GE, McDaniel MC, Sandvall BC, Liberman HA, Devireddy CM, et al. Safety of catheter-directed thrombolysis for massive and submassive pulmonary embolism: results of a multicenter registry and meta-analysis. Catheterization and Cardiovascular Interventions 2017;89(4):754-60. [DOI: 10.1002/ccd.26900] - DOI - PubMed
Boon 2020
    1. Boon GJ, Bogaard HJ, Klok FA. Essential aspects of the follow-up after acute pulmonary embolism: an illustrated review. Research and Practice in Thrombosis and Haemostasis 2020;4(6):958-68. [DOI: 10.1002/rth2.12404] - DOI - PMC - PubMed
Brailovsky 2019
    1. Brailovsky Y, Lakhter V, Weinberg I, Porcaro K, Haines J, Morris S, et al. Right ventricular outflow Doppler predicts low cardiac index in intermediate risk pulmonary embolism. Clinical and Applied Thrombosis/Hemostasis 2019;25:1076029619886062. [DOI: 10.1177/1076029619886062] - DOI - PMC - PubMed
Brailovsky 2021
    1. Brailovsky Y, Masic D, Allen S, Lakhter V, Bashir R, Forfia P, et al. Novel CT-derived parameter is associated with low cardiac index in acute pulmonary embolism. Thrombosis Research 2021;202:105-7. [DOI: 10.1016/j.thromres.2021.03.014] - DOI - PubMed
Caron 2019
    1. Caron A, Depas N, Chazard E, Yelnik C, Jeanpierre E, Paris C, et al. Risk of pulmonary embolism more than 6 weeks after surgery among cancer-free middle-aged patients. JAMA Surgery 2019;154(12):1126-32. [DOI: 10.1001/jamasurg.2019.3742] - DOI - PMC - PubMed
Cherfan 2021
    1. Cherfan P, Abou Ali AN, Zaghloul MS, Yuo TH, Phillips DP, Chaer RA, et al. Propofol administration during catheter-directed interventions for intermediate-risk pulmonary embolism is associated with major adverse events. Journal of Vascular Surgery: Venous and Lymphatic Disorders 2021;9(3):621-6. [DOI: ] - PubMed
Clark 2013
    1. Clark D, McGriffin DC, Dell'Italia LJ, Ahmed MI. Submassive pulmonary embolism: where's the tipping point? Circulation 2013;127(24):2458-64. [DOI: 10.1161/CIRCULATIONAHA.112.000859] - DOI - PubMed
COMMAND VTE Registry 2021
    1. Yamashita Y, Morimoto T, Kadota K, Takase T, Hiramori S, Kim K, et al, on behalf of the COMMAND VTE Registry Investigators. Severity of pulmonary embolism at initial diagnosis and long-term clinical outcomes: from the COMMAND VTE registry. International Journal of Cardiology 2021;343:107-13. [DOI: 10.1016/j.ijcard.2021.08.052] - DOI - PubMed
Covidence [Computer program]
    1. Covidence. Melbourne, Australia: Veritas Health Innovation, accessed 5 April 2020. Available at covidence.org.
Dhruva 2022
    1. Dhruva SS, Redberg RF. Coverage of transvenous pulmonary embolectomy – Medicare's missed opportunity for evidence generation. New England Journal of Medicine 2022;386:904-6. [DOI: 10.1056/NEJMp2114960] - DOI - PubMed
Dotter 1972
    1. Dotter CT, Rosch J, Seaman AJ, Dennis D, Massey WH. Streptokinase treatment of thromboembolic disease. Radiology 1972;102:283-90. [DOI: ] - PubMed
ESC 2014
    1. Konstrantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Nazzareno G, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. European Heart Journal 2014;35(43):3033-69. [DOI: 10.1093/eurheartj/ehu283] - DOI - PubMed
ESC 2019
    1. Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). European Heart Journal 2020;41(4):543-603. [DOI: 10.1093/eurheartj/ehz405] - DOI - PubMed
EXTRACT‐PE 2021
    1. Sista AK, Horowitz JM, Tapson VF, Rosenberg M, Elder MD, Schiro BJ, et al. Indigo aspiration system for treatment of pulmonary embolism: results of the EXTRACT-PE trial. JACC: Cardiovascular Interventions 2021;14(3):319-29. [DOI: 10.1016/j.jcin.2020.09.053] - DOI - PubMed
Furlan 2012
    1. Furlan A, Aghayev A, Chang C-CH, Patil A, Jeon KN, Park B, et al. Short-term mortality in acute pulmonary embolism: clot burden and signs of right heart dysfunction at CT pulmonary angiography. Radiology 2012;265(1):283-93. [DOI: 10.1148/radiol.12110802] - DOI - PMC - PubMed
Goldhaber 2013
    1. Goldhaber SZ. Surgical pulmonary embolectomy: the resurrection of an almost discarded operation. Texas Heart Institute Journal 2013;40(1):5-8. - PMC - PubMed
GRADEpro GDT 2015 [Computer program]
    1. GRADEpro GDT. Version accessed 20 April 2018. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015. Available at gradepro.org.
Guyatt 2011a
    1. Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso-Coello P, et al. GRADE guidelines: 4. Rating the quality of evidence – study limitations (risk of bias). Journal of Clinical Epidemiology 2011;64(4):407-15. [DOI: 10.1016/j.jclinepi.2010.07.017] - DOI - PubMed
Guyatt 2011b
    1. Guyatt GH, Oxman AD, Montorid V, Vistc G, Kunze R, Brozek J, et al. GRADE guidelines: 5. Rating the quality of evidence – publication bias. Journal of Clinical Epidemiology 2011;64(12):1277-82. [DOI: 10.1016/j.jclinepi.2011.01.011] - DOI - PubMed
Guyatt 2011c
    1. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind D, et al. GRADE guidelines 6. Rating the quality of evidence – imprecision. Journal of Clinical Epidemiology 2011;64(12):1283-93. [DOI: 10.1016/j.jclinepi.2011.01.012] - DOI - PubMed
Guyatt 2011d
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence – inconsistency. Journal of Clinical Epidemiology 2011;64(12):1294-302. [DOI: 10.1016/j.jclinepi.2011.03.017] - DOI - PubMed
Guyatt 2011e
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence – indirectness. Journal of Clinical Epidemiology 2011;64(12):1303-10. [DOI: 10.1016/j.jclinepi.2011.04.014] - DOI - PubMed
Higgins 2017
    1. Higgins JP, Altman DG, Sterne JA, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s), Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017), Cochrane, 2017. Available from training.cochrane.org/handbook/archive/v5.2.
Higgins 2021
    1. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
Ho 2019
    1. Ho KM, Rao S, Honeybul S, Zellweger R, Wibrow B, Lipman J, et al. A multicenter trial of vena cava filters in severely injured patients. New England Journal of Medicine 2019;381:328-37. [DOI: 10.1056/NEJMoa1806515] - DOI - PubMed
Hobohm 2020
    1. Hobohm L, Becattini C, Konstantinides SV, Casazza F, Lankeit M. Validation of a fast prognostic score for risk stratification of normotensive patients with acute pulmonary embolism. Clinical Research in Cardiology 2020;109(8):1008-17. [DOI: 10.1007/s00392-019-01593-w] - DOI - PMC - PubMed
Kaatz 2015
    1. Kaatz S, Ahmad D, Spyropoulos AC, Schulman S, Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis 2015;13(11):2119-26. [DOI: 10.1111/jth.13140] - DOI - PubMed
Kadakia 2022
    1. Kadakia KT, Beckman AL, Ross JS, Krumholz HM. Renewing the call for reforms to medical device safety – the case of Penumbra. JAMA Internal Medicine 2022;182(1):59-65. [PMID: 10.1001/jamainternmed.2021.6626] - DOI - PubMed
Kahn 2017
    1. Kahn SR, Hirsch AM, Akaberi A, Hernandez P, Anderson DR, Wells PS, et al. Functional and exercise limitations after a first episode of pulmonary embolism: results of the ELOPE prospective cohort study. Chest 2017;151(5):1058-68. [DOI: 10.1016/j.chest.2016.11.030] - DOI - PubMed
Kalra 2017
    1. Kalra R, Bajaj NS, Arora P, Arora G, Crosland WA, McGiffin DC. Surgical embolectomy for acute pulmonary embolism: systematic review and comprehensive meta-analyses. Annals of Thoracic Surgery 2017;103(3):982-90. [DOI: 10.1016/j.athoracsur.2016.11.016] - DOI - PubMed
Keller 2020
    1. Keller K, Hobohm L, Ebner M, Kresoja K-P, Münzel T, Konstantinides SV, et al. Trends in thrombolytic treatment and outcomes of acute pulmonary embolism in Germany. European Heart Journal 2020;41(4):522-9. [DOI: 10.1093/eurheartj/ehz236] - DOI - PubMed
Klok 2014
    1. Klok FA, Hulle T, den Exter PL, Lankeit M. The post-PE syndrome: a new concept for chronic complications of pulmonary embolism. Blood Reviews 2014;28(6):221-26. [DOI: 10.1016/j.blre.2014.07.003] - DOI - PubMed
Kucher 2006
    1. Kucher N, Rossi E, De Rosa M, Goldhaber SZ. Massive pulmonary embolism. Circulation 2006;113(4):577-82. [DOI: 10.1161/CIRCULATIONAHA.105.592592] - DOI - PubMed
Kuo 2008
    1. Kuo WT, den Bosch MA, Hofmann LV, Louie JD, Kothary N, Sze DY. Catheter-directed embolectomy, fragmentation, and thrombolysis for the treatment of massive pulmonary embolism after failure of systemic thrombolysis. Chest 2008;134(2):250-4. - PubMed
Kuo 2009
    1. Kuo WT, Gould MK, Louie JD, Rosenberg JK, Sze DY, Hoffmann LV. Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern techniques. Journal of Vascular and Interventional Radiology 2009;20(11):1431-40. [DOI: 10.1016/j.jvir.2009.08.002] - DOI - PubMed
Kuo 2010
    1. Kuo WT, Hofmann LV. Drs. Kuo and Hofmann respond. Journal of Vascular and Interventional Radiology 2010;21(11):1776-7. [PMID: ] - PubMed
Lang 2014
    1. Lange IM, Madani M. Update on chronic thromboembolic pulmonary hypertension. Circulation 2014;130(6):508-13. [DOI: 10.1161/CIRCULATIONAHA.114.009309] - DOI - PubMed
Lefebvre 2021
    1. Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M-I, et al. Chapter 4: Searching for and selecting studies. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
Madani 2016
    1. Madani M, Mayer E, Fadel E, Jenkins DP. Pulmonary endarterectomy. Annals of the American Thoracic Society 2016;13(3):S240-7. [DOI: 10.1513/AnnalsATS.201601-014AS] - DOI - PubMed
Manchec 2019
    1. Manchec B, Liu B, Tran T, Zuchowski C, Guruvadoo K, Parente R, et al. Sedation with propofol during catheter-directed thrombolysis for acute submassive pulmonary embolism is associated with increased mortality. Journal of Vascular and Interventional Radiology 2019;30:1719-24. [DOI: 10.1016/j.jvir.2019.08.009] - DOI - PubMed
Marti 2014
    1. Marti C, John G, Konstantinides S, Combescure C, Sanchez O, Lankeit M, et al. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. European Heart Journal June 2014;36(10):605-14. [DOI: 10.1093/eurheartj/ehu218] - DOI - PMC - PubMed
Mathai 2016
    1. Mathai SC, Ghofrani H-A, Mayer E, Pepke-Zaba J, Nikkho S, Simmonneau G. Quality of life in patients with chronic thromboembolic pulmonary hypertension. European Respiratory Journal 2016;48(6):1-12. [DOI: 10.1183/13993003.01626-2015] - DOI - PMC - PubMed
McFadden 2010
    1. McFadden PM, Ochsner JL. Aggressive approach to pulmonary embolectomy for massive acute pulmonary embolism: a historical and contemporary perspective. Mayo Clinic Proceedings 2010;85(9):782-4. [DOI: 10.4065/mcp.2010.0481] - DOI - PMC - PubMed
Mehran 2011
    1. Mehran R, Rao SV, Bhatt DL, Gibson M, Caixeta A, Eikelboom J, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the bleeding academic research consortium. Circulation 2011;123:2736-47. [DOI: 10.1161/CIRCULATIONAHA.110.009449] - DOI - PubMed
Meinel 2015
    1. Meinel FG, Nance Jr JW, Schoepf UJ, Hoffmann VS, Thierfelder KM, Costello P, et al. Predictive value of computed tomography in acute pulmonary embolism: systematic review and meta-analysis. American Journal of Medicine 2015;128(7):747-59. [EMBASE: 10.1016/j.amjmed.2015.01.023] - PubMed
Meyer 2014
    1. Meyer G, Vicaut E, Danays MD, Agnelli G, Becattini C, Beyer-Westendorf J, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. New England Journal of Medicine 2014;370(15):1402-11. [DOI: 10.1056/NEJMoa1302097] - DOI - PubMed
Miró 2021
    1. Miró Ò, Jiménez S, Mebazaa A, Freund Y, Burillo-Putze G, Martín A, et al. Pulmonary embolism in patients with COVID-19: incidence, risk factors, clinical characteristics, and outcome. European Heart Journal 2021;42(33):3127-42. [DOI: 10.1093/eurheartj/ehab314] - DOI - PMC - PubMed
NCT03426124
    1. NCT03426124. An international pulmonary embolism registry using EKOS (KNOCOUT PE). clinicaltrials.gov/ct2/show/NCT03426124 (first received 8 February 2018). [CLINICALTRIALS.GOV: NCT03426124]
NCT03761173
    1. NCT03761173. FlowTriever All-Comer Registry for patient safety and hemodynamics (FLASH). clinicaltrials.gov/ct2/show/NCT03761173 (first received 3 December 2018). [CLINICALTRIALS.GOV IDENTIFIER: NCT03761173]
NCT04248868
    1. NCT04248868. tPA by endovascular administration for the treatment of submassive PE using CDT for the reduction of thrombus burden (RESCUE). clinicaltrials.gov/ct2/show/NCT04248868 (first received 30 January 2020). [CLINICALTRIALS.GOV IDENTIFIER: NCT04248868]
NCT04795167
    1. NCT04795167. FLowTriever for acute massive pulmonary embolism (FLAME). clinicaltrials.gov/ct2/show/NCT04795167 (first received 12 March 2021). [CLINICALTRIALS.GOV IDENTIFIER: NCT04795167]
NCT04798261
    1. NCT04798261. Study of the long-term safety and outcomes of treating pulmonary embolism with the Indigo Aspiration System. clinicaltrials.gov/ct2/show/NCT04798261 (first received 15 March 21).
PEITHO 2014
    1. Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, et al, on behalf of the PEITHO investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. New England Journal of Medicine 2014;370(15):1402-11. [DOI: 10.1056/NEJMoa1302097] - DOI - PubMed
PERFECT 2015
    1. Kuo WT, Banerjee A, Kim PS, DeMarco FJ Jr, Levy JR, Facchini FR, et al. Pulmonary embolism response to fragmentation, embolectomy, and catheter thrombolysis (PERFECT): initial results from a prospective multicenter registry. Chest 2015;148(3):66773. [CLINICALTRIAL.GOV: NCT01097928] [DOI: 10.1378/chest.15-0119] - DOI - PubMed
Pesavento 2017
    1. Pesavento R, Filippi L, Palla A, Visonà A, Bova C, Marzolo M, et al. Impact of residual pulmonary obstruction on the long-term outcome of patients with pulmonary embolism. European Respiratory Journal 2017;49:1601980. [DOI: 10.1183/13993003.01980-2016] - DOI - PubMed
Piazza 2010
    1. Piazza G, Goldhaber SZ. Management of submassive pulmonary embolism. Circulation 2010;122(11):1124-9. [DOI: 10.1161/CIRCULATIONAHA.110.961136] - DOI - PMC - PubMed
PREPIC2 2015
    1. Mismetti P, Laporte S, Pellerin O, Ennezat PV, Couturaud F, Elias A, et al, on behalf of the PREPIC2 study group. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial. JAMA 2015;313(16):1627-35. [DOI: 10.1001/jama.2015.3780] - DOI - PubMed
Review Manager 2020 [Computer program]
    1. Review Manager 5 (RevMan 5). Version 5.4. Copenhagen: Nordic Cochrane Centre, the Cochrane Collaboration, 2020.
Samuels 2019
    1. Samuels J, Lawson PJ, Morton AP, Hansen KC, Sauaia A, Schoen JA, et al. Prospective assessment of fibrinolysis in morbid obesity: tissue plasminogen activator resistance improves after bariatric surgery. Surgery for Obesity and Related Diseases 2019;15(7):1153-9. [DOI: 10.1016/j.soard.2019.03.048] - DOI - PMC - PubMed
Sardar 2020
    1. Sardar P, Piazza G, Goldhaber SZ, Liu P-Y, Prabhu W, Soukas P, et al. Predictors of treatment response following ultrasound-facilitated catheter-directed thrombolysis for submassive and massive pulmonary embolism: a SEATTLE II substudy. Circulation: Cardiovascular Interventions 2020;13(6):1-6. [DOI: 10.1161/CIRCINTERVENTIONS.119.008747] - DOI - PubMed
Schmitz‐Rode 1998
    1. Schmitz-Rode T, Kilbinger M, Gunther RW. Simulated flow pattern in massive pulmonary embolism: significance for selective intrapulmonary thrombolysis. Cardiovascular and Interventional Radiology 1998;21(3):199-204. [DOI: 10.1007/s002709900244] - DOI - PubMed
Schulman 2005
    1. Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. Journal of Thrombosis and Haemostasis 2005;3(4):692-4. [DOI: 10.1111/j.1538-7836.2005.01204.x] - DOI - PubMed
SEATTLE II 2015
    1. Piazza G, Hohlfelder B, Jaff MR, Ouriel K, Engelhardt TC, Sterling KM, et al. A prospective, single-arm, multicenter trial of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis for acute massive and submassive pulmonary embolism: the SEATTLE II Study. JACC: Cardiovascular Interventions 2015;8(10):1382-92. [DOI: 10.1016/j.jcin.2015.04.020] - DOI - PubMed
Secemsky 2018
    1. Secemsky E, Chang Y, Jain CC, Beckman JA, Giri J, Jaff MR, et al. Contemporary management and outcomes of patients with massive and submassive pulmonary embolism. American Journal of Medicine 2018;131(12):1506-14. [DOI: 10.1016/j.amjmed.2018.07.035] - DOI - PubMed
SUNSET sPE 2021
    1. Avgerinos ED, Jaber W, Lacomis J, Markel K, McDaniel M, Rivera-Lebron BN, et al, on behalf of SUNSET sPE Collaborators. Randomized trial comparing standard versus ultrasound-assisted thrombolysis for submassive pulmonary embolism: the SUNSET sPE trial. JACC: Cardiovascular Interventions 2021;14(12):1364-73. [DOI: 10.1016/j.jcin.2021.04.049] - DOI - PMC - PubMed
TIPES 2010
    1. Becattini C, Agnelli G, Salvi A, Grifoni S, Pancaldi LG, Enea I, et al, on behalf of the TIPES Study Group. Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism. Thrombosis Research 2010;125(3):e82-6. [DOI: 10.1016/j.thromres.2009.09.017] - DOI - PubMed
Todoran 2018
    1. Todoran TM, Giri J, Barnes GD, Rosovsky RP, Chang Y, Jaff MR, et al, on behalf of the PERT Consortium. Treatment of submassive and massive pulmonary embolism: a clinical practice survey from the second annual meeting of the Pulmonary Embolism Response Team Consortium. Journal of Thrombosis and Thrombolysis 2018;46(1):39-49. [DOI: 10.1007/s11239-018-1659-5] - DOI - PubMed
Virani 2021
    1. Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, et al. Heart disease and stroke statistics – 2021 update: a report from the American Heart Association. Circulation 2021;143(8):e254-743. [DOI: 10.1161/CIR.0000000000000950] - DOI - PubMed
Wood 2002
    1. Wood K. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest 2002;121(3):877-905. - PubMed
Young 2020
    1. Young T, Srinam KB. Vena caval filters for the prevention of pulmonary embolism. Cochrane Database of Systematic Reviews 2020, Issue 10. Art. No: CD006212. [DOI: 10.1002/14651858.CD006212.pub5] - DOI - PMC - PubMed
Yuriditsky 2020
    1. Yuriditsky E, Mitchell OJ, Sista AK, Xia Y, Sibley RA, Zhong J, et al. Right ventricular stroke distance predicts death and clinical deterioration in patients with pulmonary embolism. Thrombosis Research 2020;195:29-34. [DOI: 10.1016/j.thromres.2020.06.049] - DOI - PubMed
Zuo 2021
    1. Zuo Z, Yue J, Dong BR, Wu T, Liu GJ, Hao Q. Thrombolytic therapy for pulmonary embolism. Cochrane Database of Systematic Reviews 2021, Issue 4. Art. No: CD004437. [DOI: 10.1002/14651858.CD004437.pub6] - DOI - PMC - PubMed

References to other published versions of this review

Harvey 2018
    1. Harvey JJ, Makris GC, Uberoi R. Catheter-directed therapies for the treatment of massive and submassive acute pulmonary embolism. Cochrane Database of Systematic Reviews 2018, Issue 7. Art. No: CD013083. [DOI: 10.1002/14651858.CD013083] - DOI - PMC - PubMed

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