Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis

Abstract

Background: Therapeutic options for intermediate- or high-risk pulmonary embolism (PE) include anticoagulation, systemic thrombolysis and catheter-directed thrombolysis (CDT); however, the role of CDT remains controversial. We sought to compare the efficacy and safety of CDT with other therapeutic options using network meta-analysis.

Methods: We searched PubMed (MEDLINE), Embase, ClinicalTrials.gov and Cochrane Library from inception to Oct. 18, 2022. We included randomized controlled trials and observational studies that compared therapeutic options for PE, including anticoagulation, systemic thrombolysis and CDT among patients with intermediate- or high-risk PE. The efficacy outcome was in-hospital death. Safety outcomes included major bleeding, intracerebral hemorrhage and minor bleeding.

Results: We included data from 44 studies, representing 20 006 patients. Compared with systemic thrombolysis, CDT was associated with a decreased risk of death (odd ratio [OR] 0.43, 95% confidence interval [CI] 0.32-0.57), intracerebral hemorrhage (OR 0.44, 95% CI 0.29-0.64), major bleeding (OR 0.61, 95% CI 0.53-0.70) and blood transfusion (OR 0.46, 95% CI 0.28-0.77). However, no difference in minor bleeding was observed between the 2 therapeutic options (OR 1.11, 95% CI 0.66-1.87). Compared with anticoagulation, CDT was also associated with decreased risk of death (OR 0.36, 95% CI 0.25-0.52), with no increased risk of intracerebral hemorrhage (OR 1.33, 95% CI 0.63-2.79) or major bleeding (OR 1.24, 95% CI 0.88-1.75).

Interpretation: With moderate certainty of evidence, the risk of death and major bleeding complications was lower with CDT than with systemic thrombolysis. Compared with anticoagulation, CDT was associated with a probable lower risk of death and a similar risk of intracerebral hemorrhage, with moderate certainty of evidence. Although these findings are largely based on observational data, CDT may be considered as a first-line therapy in patients with intermediate- or high-risk PE.

Protocol registration: PROSPERO - CRD42020182163.

Figure 1:

Flow chart. *Studies could be excluded for more than 1 reason. Note: NOS = Newcastle–Ottawa Scale.

Figure 2:

Net graphs of primary and secondary outcomes, showing the number of participants included in analyses of (A) all-cause death, (B) major bleeding, (C) intracranial hemorrhage, (D) minor bleeding, (E) blood transfusion and (F) gastrointestinal bleeding. Note: CDT = catheter-directed thrombolysis. The size of the red circle and corresponding sample size indicates the number of participants who received that treatment. The number of participants along the triangle sides indicates those involved in comparison of treatment arms. The thickness of the sides in the triangle indicates how many studies were conducted between treatments. As the number of articles comparing treatments increases, the thickness increases. Some studies included 3 treatment arms.

Figure 3:

Network meta-analysis of the association between treatment for pulmonary embolism and all-cause death. Size of squares is proportional to the weight of each arm. Decreased or increased risk of the outcome is of the first type of treatment in comparison, relative to the second type of treatment. The p value indicates the probability of observing the differences between direct and indirect treatment effects. The presence of incoherence is indicated by a p value less than 0.05. Note: AC = anticoagulation, CDT = catheter-directed thrombolysis, CI = confidence interval, OR = odds ratio, ST = systemic thrombolysis.

Figure 4:

Network meta-analysis of the association between treatment for pulmonary embolism and major bleeding. Size of squares is proportional to the weight of each arm. Decreased or increased risk of the outcome is of the first type of treatment in comparison, relative to the second type of treatment. The p value indicates the probability of observing the differences between direct and indirect treatment effects. The presence of incoherence is indicated by a p value less than 0.05. Note: AC = anticoagulation, CDT = catheter-directed thrombolysis, CI = confidence interval, OR = odds ratio, ST = systemic thrombolysis.

Figure 5:

Network meta-analysis of the association between treatment for pulmonary embolism and intracranial hemorrhage. Size of squares is proportional to the weight of each arm. Decreased or increased risk of the outcome is of the first type of treatment in comparison, relative to the second type of treatment. The p value indicates the probability of observing the differences between direct and indirect treatment effects. The presence of incoherence is indicated by a p value less than 0.05. Note: AC = anticoagulation, CDT = catheter-directed thrombolysis, CI = confidence interval, OR = odds ratio, ST = systemic thrombolysis.

Figure 6:

Network meta-analysis of the association between treatment for pulmonary embolism and minor bleeding. Size of squares is proportional to the weight of each arm. Decreased or increased risk of the outcome is of the first type of treatment in comparison, relative to the second type of treatment. The p value indicates the probability of observing the differences between direct and indirect treatment effects. The presence of incoherence is indicated by a p value less than 0.05. Note: AC = anticoagulation, CDT = catheter-directed thrombolysis, CI = confidence interval, OR = odds ratio, ST = systemic thrombolysis.