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Systemic Thrombolytic Therapy for Acute Pulmonary Embolism: A Systematic Review and Meta-Analysis
Study Questions:
What are the risks and benefits of thrombolytic therapy in the management of patients with acute pulmonary embolism (PE)?
Methods:
The authors did a systematic review of randomized controlled studies comparing systemic thrombolytic therapy plus anticoagulation with anticoagulation alone in patients with acute PE. Fifteen trials involving 2,057 patients were included in a meta-analysis. The primary efficacy outcome was early all-cause mortality (in-hospital or within 30 days of inclusion). Three secondary efficacy outcomes were considered: recurrent PE confirmed by a validated diagnostic examination, death related to PE, and the combination of all-cause death or clinical deterioration requiring rescue treatment (vasopressors, mechanical ventilation, cardiopulmonary resuscitation, systemic rescue thrombolysis, or embolectomy).
Results:
Compared with heparin, thrombolytic therapy was associated with a significant reduction of overall mortality (2.3% vs. 3.9% in controls; odds ratio [OR], 0.59; 95% confidence interval [CI], 0.36-0.96). This reduction was not statistically significant after exclusion of studies including high risk PE (OR, 0.64; 95% CI, 0.35-1.17). Thrombolytic therapy was associated with a significant reduction in the combined endpoint of death or treatment escalation (OR, 0.34; 95% CI, 0.22-0.53), PE-related mortality (OR, 0.29; 95% CI, 0.14-0.60), and PE recurrence (OR, 0.50; 95% CI, 0.27-0.94). Major hemorrhage (OR, 2.91; 95% CI, 1.95-4.36) and fatal or intracranial bleeding (OR, 3.18; 95% CI, 1.25-8.11) were significantly more frequent among patients receiving thrombolysis.
Conclusions:
Thrombolytic therapy reduces total mortality, PE recurrence, and PE-related mortality in patients with acute PE. The decrease in overall mortality is, however, not significant in hemodynamically stable patients with acute PE. Thrombolytic therapy is associated with an increase of major and fatal or intracranial hemorrhage.
Perspective:
In the absence of contraindications, current guidelines recommend thrombolytic therapy for patients with high-risk PE, which was confirmed in this review based on a total of 219 subjects, in which all but eight were published between 1970 and 1979 (OR, 0.48; 95% CI, 0.20-1.15). The analysis included the very large PEITHO study, published in 2014, in which those with high-risk PE were excluded. Thrombolysis is not recommended on a routine basis for patients with intermediate-risk PE, but may be considered following individual risk-to-benefit analysis. Another recent meta-analysis focused on the impact of right ventricular (RV) dysfunction on outcome and concluded that those with hemodynamically stable PE and RV dysfunction benefit from thrombolytic therapy with a meaningful reduction in overall mortality, but with a significant risk of major bleeding including intracranial hemorrhage, particularly in patients older than 65 years. These reviews should not change clinical guidelines, but do provide evidence that a randomized, placebo-controlled trial incorporating the hemodynamically stable PE with RV dysfunction is needed.
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