Systematic Review of Treatment for Massive and Submassive Pulmonary Embolism

Abstract Introduction: Anticoagulation is the standard treatment for pulmonary embolism (PE). In patients presenting with massive or submassive PE, the addition of systemic thrombolytics (STL) and catheter directed therapies (CDT) may also be considered. However, there is uncertainty about the benefits and risks of these treatments, and no randomized trials have compared STL to CDT. Aim: We reviewed the risks and benefits of STL and CDT in the management of patients with massive or submassive PE. Methods: A systematic literature search was conducted using MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and bibliographies of relevant studies and reviews. Randomized trials and cohort studies were eligible. Registries and studies with fewer than 10 patients were ineligible. Pooled proportions and their associated 95% confidence intervals (CI) for mortality, major bleeding, intracranial hemorrhage (ICH), recurrent PE, and fatal recurrent PE were calculated. Results: A total of 52 studies were included in the analyses: 19 studies evaluating STL; 18 studies using CDT; 5 studies using the AngioJet rheolytic thrombectomy system; and 10 studies using ultrasound-assisted CDT. The pooled proportion of outcomes for patients receiving STL were: 4.46% (95% CI: 3.04-6.13%) for mortality; 11.70% (95% CI: 7.78-16.90%) for major bleeding; 1.99% (95% CI: 1.06-3.20%) for ICH; 3.92% (95% CI: 2.56-5.55%) for recurrent PE; and 1.04% (95% CI: 0.42-1.94%) for fatal recurrent PE. For patients receiving CDT, the pooled proportion of outcomes were: 9.64% (95% CI: 5.93-14.13%) for mortality; 5.17% (95% CI: 2.18-9.33%) for major bleeding; 1.29% (95% CI: 0.48-2.48%) for ICH; 2.76% (95% CI: 1.36-4.63%) for recurrent PE; and 1.56% (95% CI: 0.53-3.12%) for fatal recurrent PE. For patients receiving AngioJet CDT, the pooled proportion of outcomes were: 10.18% (95% CI: 3.68-19.42%) for mortality; 9.14% (95% CI: 0.88-24.70%) for major bleeding; 2.30% (95% CI: 0.34-5.96%) for ICH; 4.84% (95% CI: 1.62-9.66%) for recurrent PE; and 4.84% (95% CI: 1.62-9.66%) for fatal recurrent PE. In patients receiving ultrasound-assisted CDT, the pooled proportion of outcomes were: 4.17% (95% CI: 1.64-7.79%) for mortality; 4.88% (95% CI: 2.48-8.05%) for major bleeding; 0.63% (95% CI: 0.10-1.59%) for ICH; 1.39% (95% CI: 0.48-2.77%) for recurrent PE; and 1.21% (95% CI: 0.35-2.56%) for fatal recurrent PE. Conclusions: Our results suggest that all-cause mortality rates in patients with massive or submassive PE are similar between STL and ultrasound-assisted CDT and are lower than other types of CDT. In general, major bleeding rates were lower in CDT based groups than in STL. Importantly, ICH rates in CDT based treatment strategies were also lower than STL therapy. Randomized trials comparing STL and CDT would help solidify the role of these treatment strategies in patients with massive and submassive PE. Disclosures Carrier: BMS: Research Funding; Leo Pharma: Research Funding.