Incidence of Mortality and Complications in High-Risk Pulmonary Embolism: A Systematic Review and Meta-Analysis

Abstract

Background: The relationship between the early hemodynamic consequences of acute pulmonary embolism (PE) and short-term morbidity and mortality has long been recognized. The mortality incidence and other complications after high-risk (massive) PE, the most severe category of the disease, are summarized in this meta-analysis.

Methods: A systematic review and meta-analysis of studies reporting on patients with massive PE indexed by PubMed and the Cochrane Library over a 10-year period (2010-2020) was conducted. Studies with adequate information to specify a cohort of patients with high-risk PE defined by the American Heart Association and European Society of Cardiology criteria and their clinical outcomes were included. Incidences were calculated as weighted averages with 95% CIs.

Results: A total of 27 publications spanning 1517 patients were identified that met the search criteria for high-risk PE. In-hospital all-cause mortality averaged 28.3% (95% CI, 20.9%-37.0%) in patients at high risk, comparable to the 30-day all-cause mortality of 30.2% (95% CI, 22.3%-39.6%). In-hospital major bleeding was 13.8% (95% CI, 9.3%-20.0%), and intracranial hemorrhage was reported in 3.6% (95% CI, 2.2%-5.9%). The risk of bias in publications was graded as low-to-moderate, with substantial heterogeneity among the studies.

Conclusions: This systematic review and meta-analysis provided low-quality to moderate-quality evidence documenting mortality, major bleeding, and other complications in patients meeting the American Heart Association and European Society of Cardiology criteria for high-risk PE. This information was used to inform the design of the FLowTriever for Acute Massive Pulmonary Embolism (FLAME) study (NCT04795167), a study evaluating an advanced therapy for patients with high-risk PE.

Keywords: high-risk; massive; mechanical thrombectomy; pulmonary embolism; thromboembolectomy; thrombolysis.

Graphical abstract

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram demonstrating the selection process for included publications. The arrows indicate the direction of workflow. The numbers indicate the number of publications remaining at each step in the process. MPE, massive pulmonary embolism; PE, pulmonary embolism.

Figure 2

In-hospital mortality weighted average, 95% CIs, and forest plot for patients with high-risk pulmonary embolism. Additional information is presented in Supplemental Table S3. AC Grp., anticoagulation group; AC & ECMO, anticoagulation and extracorporeal membrane oxygenation group; Surg. Embol. Grp., surgical embolization group; Sys. Throm. Grp., systemic thrombolysis group.

Figure 3

Mortality weighted average through 30 days, 95% CIs, and forest plot for patients with high-risk pulmonary embolism. Additional information is presented in Supplemental Table S3. AC Grp., anticoagulation group; Echocard. Grp., echocardiology group; HM Grp., hemodynamic monitoring group; Surg. Embol. Grp., Surgical Embolization Group; Sys. Throm. Grp., systemic thrombolysis group.

Figure 4

Weighted averages, 95% CIs, and forest plot of publications specifying major (BARC 3b) bleeding incidence in patients with high-risk pulmonary embolism. Additional information is presented in Supplemental Table S1. AC Grp., anticoagulation group; AC & ECMO, anticoagulation and extracorporeal membrane oxygenation group; BARC, Bleeding Academic Research Consortium; Surg. Embol. Grp., surgical embolization group.

Figure 5

Weighted averages, 95% CIs, and forest plot for major bleeding (irrespective of BARC) in patients with high-risk pulmonary embolism. Additional information is presented in Supplemental Table S1. AC Grp., anticoagulation group; AC & ECMO, anticoagulation and extracorporeal membrane oxygenation group; BARC, Bleeding Academic Research Consortium; Surg. Embol. Grp., surgical embolization group.

Central Illustration

Literaturesearch strategy and results.