Outcomes With Treatment Interventions for Clot-In-Transit in Patients With Pulmonary Embolism: A Meta-Analysis

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J INVASIVE CARDIOL 2024. doi:10.25270/jic/24.00089. Epub May 21, 2024.

Objectives. Clot-in-transit (CIT) in patients with pulmonary embolism (PE) has been associated with a high mortality rate and poor prognosis. The aim of this study was to evaluate the pooled efficacy of each of the 4 interventions (anticoagulation [AC] alone, systemic thrombolytic [ST] therapy, surgical thrombectomy, and catheter-based thrombectomy [CBT]) using mortality as the primary outcome.  

Methods. A time limited search until March 28, 2024 was conducted using PubMed (National Institutes of Health) and EMBASE (Elsevier) databases.

Results. Thirteen studies (6 retrospective, 4 non-randomized prospective, and 3 pooled studies of case-reports) were included in the calculation of weighted proportion of mortality, including a total of 492 patients with CIT and PE with a mean age of 60.6 years; 50.1% were males. ST was the most frequently used treatment intervention (38.2%), followed by surgical thrombectomy (33.8%), AC alone (22.6%), and CBT (5.9%). The unweighted mortality was highest with AC alone 32.4% (36/111), followed by surgical thrombectomy 23.2% (38/164), CBT 20.7% (6/29), and ST 13.8% (26/188). The weighted mortality for AC alone was 35% (95% CI, 21% to 49%; 12 studies), surgical thrombectomy was 31% (95% CI, 16% to 47%; 12 studies), CBT was 20% (95% CI, 6% to 34%; 3 studies), and ST was 12% (95% CI, 5% to 19%; 12 studies).

Conclusions. In this meta-analysis of patients with CIT and PE, the highest mortality was observed with AC alone, followed by surgical thrombectomy, CBT, and ST therapy. However, there remains a need for randomized clinical trial data to determine the best treatment.

Clot-in-transit (CIT) in patients with pulmonary embolism (PE) has been associated with a high mortality rate and poor prognosis.^1,2 Given the rarity of CIT and the paucity of available literature, the optimal treatment is still unknown. Currently, the 4 most frequently employed treatment modalities in patients with CIT and acute PE include anticoagulation (AC) alone, systemic thrombolytic (ST) therapy, surgical thrombectomy, and catheter-based thrombectomy (CBT), with the latter becoming increasingly common. The aim of this study was to evaluate the pooled efficacy of each of the 4 interventions using mortality as the primary outcome.  

This meta-analysis and systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.³ This analysis was not considered for institutional review board review as this was a study level meta-analysis of published clinical data. A time limited search until March 28, 2024 was conducted using PubMed (National Institutes of Health) and EMBASE (Elsevier) databases. The following Medical Education Subject Headings were used for this search: “right heart thrombus”, “pulmonary embolism”, “clot-in transit”, “anticoagulation alone”, “systemic fibrinolytic/thrombolytic therapy”, “surgical thrombectomy”, and “mechanical/catheter-based thrombectomy”. We also considered references of the eligible studies to identify further studies.

The inclusion criteria were prospective and retrospective observational studies as well as studies that pooled case reports and reported mortality on 1 of 4 treatment modalities (AC alone, ST therapy, surgical thrombectomy, or catheter-based thrombectomy). Non-relevant studies were excluded based on title followed by abstract. Full-text studies were then screened for final selection based on above-mentioned, pre-specified inclusion criteria. Two reviewers (M.H.M. and R.S.Z.) independently reviewed the literature and extracted and entered data. Discrepancies were resolved by the senior author (S.B.).

The efficacy outcome was all-cause mortality (both weighted and unweighted). Continuous variables were reported as mean with standard deviation, and categorical variables were expressed as frequency/percentage. The overall weighted pooled proportions of mortality were calculated using a random-effects meta-analysis model based on the individual study data for each outcome. The weighted meta-analysis for proportion was conducted using Stata version 17.0 software (Stata Corporation).

Thirteen studies (6 retrospective, 4 non-randomized prospective, and 3 pooled studies of case-reports) were included in the calculation of weighted proportion of mortality, including a total of 492 patients with CIT and PE with a mean age of 60.6 years; 50.1% were males (references for the included studies are shown in the Figure). ST was the most frequently used treatment intervention (38.2%), followed by surgical thrombectomy (33.8%), AC alone (22.6%), and CBT (5.9%). Overall mortality (unweighted) was 21.5% (106/492). The unweighted mortality was highest with AC alone 32.4% (36/111), followed by surgical thrombectomy 23.2% (38/164), CBT 20.7% (6/29), and ST 13.8% (26/188) (Figure A). The overall weighted mortality using single arm meta-analysis was 22% (95% CI: 14% to 29%; 13 studies) (Figure A and B). The weighted proportions of mortality for each treatment modality were as follows: AC alone was 35% (95% CI: 21% to 49%; 12 studies), surgical thrombectomy was 31% (95% CI: 16% to 47%; 12 studies), CBT was 20% (95% CI: 6% to 34%; 3 studies), and ST was 12% (95% CI: 5% to 19%; 12 studies) (Figure A and B).

In this large series of patients with CIT in patients with PE, the mortality was very high (around 22%) and in the range for high-risk PE. ST was associated with a lowest risk of mortality, followed by CBT, surgical thrombectomy, and AC alone.

This is the largest pooled analysis and the first study to evaluate mortality associated with different treatment modalities in patients with CIT and PE. Our study confirms the previously reported high mortality rate (20.4%) among patients with CIT and PE,⁴ emphasizing the challenges in treatment due to the high mortality, the potential for embolization, and uncertainty regarding optimal timing and treatment modality. We found that ST and CBT have the lowest rate of mortality, but the analysis of CBT was limited by the small sample size (n = 29). With the growing interest in CBT, ^5,6 it may present a less invasive alternative to surgery with a substantially lower bleeding risk.⁷ However, the paucity of reported bleeding outcomes in the included studies precluded a comprehensive comparison of major bleeding rates associated with each intervention. Future studies should consistently report major bleeding rates to facilitate a more nuanced evaluation of safety and efficacy among different treatment modalities.

The 2019 European Society of Cardiology guidelines for acute PE give ST therapy a Class I recommendation and give interventional thrombus removing therapy (CBT or surgical thrombectomy) a Class IIa recommendation in hemodynamically deteriorating PE.⁸ However, these guidelines do not provide specific recommendations for the treatment of CIT and PE. Our study fills this knowledge gap by offering insights into potential treatment interventions for CIT and PE. As we await the results from additional prospective studies, our findings may serve as the best available evidence to inform and guide treatment strategies in the interim. This study was not designed to compare mortality rates of the different treatment modalities against each other, as treatment selection bias and non-standardization of inclusion inherent to a retrospective analysis preclude such an analysis. Although the data on CBT for CIT and PE was limited, its use is projected to become more common with more prevalent use in patients with PE.⁹

Limitations. The results should be interpreted in light of important limitations. First, head-to-head comparison studies of different treatments for CIT and PE was limited. Second, our analysis included observational studies, case studies, and case series, and as such has inherent selection, reporting, and ascertainment bias. Third, studies did not report major bleeding and thus we were unable to perform a more nuanced evaluation of safety and efficacy among different treatment modalities.

In this meta-analysis encompassing 492 patients with CIT and PE, a considerably high mortality rate of approximately 22%, with the highest mortality associated with AC alone, followed by surgical thrombectomy, CBT, and ST therapy, was observed. However, there remains a need for randomized clinical trial data to determine the best treatment.

Dr Maqsood and Dr Zhang contributed to this work equally.

From the ¹Department of Cardiology, DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Texas, USA; ²Division of Cardiovascular Medicine, New York University Grossman School of Medicine, New York, New York, USA; ³Division of Cardiovascular Medicine, University at Buffalo, Gates Vascular Institute, Buffalo General Medical Center, Buffalo, New York, USA; ⁴Division of Cardiology, Department of Medicine, New York-Presbyterian/Columbia University Irving Medical Center, New York, New York, USA.

Disclosures: Dr. Bangalore serves on the advisory boards of Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, and Truvic. The remaining authors report no financial relationships or conflicts of interest regarding the content herein.

Address for correspondence: Sripal Bangalore, MD, MHA, New York University School of Medicine, New York, NY 10016, USA. Email: sripalbangalore@gmail.com; X: @sripalbangalore; @haisummaqsood