Thrombolytics in Pulmonary Embolism Associated with Lower Mortality, Increased Bleeding

Clinical question: What are the mortality benefits and bleeding risks associated with thrombolytic therapy, compared with other anticoagulants, in pulmonary embolism (PE)?

Background: Thrombolytics are not routinely administered for PE but can be considered in patients with hemodynamic instability with massive PE and those not responding to anticoagulation.

Study design: Meta-analysis.

Setting: Sixteen randomized clinical trials (RCTs) occurring in a variety of settings.

Synopsis: Trials involving 2,115 patients (thrombolytic therapy cohort 1,061; anticoagulation cohort 1,054) with PE were studied, with special attention given to those patients with intermediate risk PEs defined by subclinical cardiovascular compromise. Thrombolytics were compared with low molecular weight heparin, unfractionated heparin, vitamin K antagonists, and fondaparinux. The primary outcomes were all-cause mortality and major bleeding. Secondary outcomes included risk of recurrence of the PE and intracranial hemorrhage.

Thrombolytic therapy was associated with lower all-cause mortality and with higher risk of bleeding. There was a 9.24% rate of major bleeding in the thrombolytic therapy cohort and a 3.42% rate in the anticoagulation cohort. Intracranial hemorrhage was greater in the thrombolytic therapy cohort (1.46% vs. 0.19%). Patients with intermediate risk PE had greater major bleeding rate (7.74% vs. 2.25%) and lower mortality (1.39% vs. 2.92%) with thrombolytics compared to anticoagulation. A net clinical benefit calculation (mortality benefit accounting for intracranial hemorrhage risk) was performed and demonstrated a net clinical benefit of 0.81% (95% CI, 0.65%-1.01%) for those patients who received thrombolytics versus other anticoagulation.

Bottom line: This study suggested a mortality benefit of thrombolytics overall, including those patients with intermediate risk PE.

Citation: Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014;311(23):2414-2421.

Clinical question: What are the mortality benefits and bleeding risks associated with thrombolytic therapy, compared with other anticoagulants, in pulmonary embolism (PE)?

Background: Thrombolytics are not routinely administered for PE but can be considered in patients with hemodynamic instability with massive PE and those not responding to anticoagulation.

Study design: Meta-analysis.

Setting: Sixteen randomized clinical trials (RCTs) occurring in a variety of settings.

Synopsis: Trials involving 2,115 patients (thrombolytic therapy cohort 1,061; anticoagulation cohort 1,054) with PE were studied, with special attention given to those patients with intermediate risk PEs defined by subclinical cardiovascular compromise. Thrombolytics were compared with low molecular weight heparin, unfractionated heparin, vitamin K antagonists, and fondaparinux. The primary outcomes were all-cause mortality and major bleeding. Secondary outcomes included risk of recurrence of the PE and intracranial hemorrhage.

Thrombolytic therapy was associated with lower all-cause mortality and with higher risk of bleeding. There was a 9.24% rate of major bleeding in the thrombolytic therapy cohort and a 3.42% rate in the anticoagulation cohort. Intracranial hemorrhage was greater in the thrombolytic therapy cohort (1.46% vs. 0.19%). Patients with intermediate risk PE had greater major bleeding rate (7.74% vs. 2.25%) and lower mortality (1.39% vs. 2.92%) with thrombolytics compared to anticoagulation. A net clinical benefit calculation (mortality benefit accounting for intracranial hemorrhage risk) was performed and demonstrated a net clinical benefit of 0.81% (95% CI, 0.65%-1.01%) for those patients who received thrombolytics versus other anticoagulation.

Bottom line: This study suggested a mortality benefit of thrombolytics overall, including those patients with intermediate risk PE.

Citation: Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014;311(23):2414-2421.

Clinical question: What are the mortality benefits and bleeding risks associated with thrombolytic therapy, compared with other anticoagulants, in pulmonary embolism (PE)?

Background: Thrombolytics are not routinely administered for PE but can be considered in patients with hemodynamic instability with massive PE and those not responding to anticoagulation.

Study design: Meta-analysis.

Setting: Sixteen randomized clinical trials (RCTs) occurring in a variety of settings.

Synopsis: Trials involving 2,115 patients (thrombolytic therapy cohort 1,061; anticoagulation cohort 1,054) with PE were studied, with special attention given to those patients with intermediate risk PEs defined by subclinical cardiovascular compromise. Thrombolytics were compared with low molecular weight heparin, unfractionated heparin, vitamin K antagonists, and fondaparinux. The primary outcomes were all-cause mortality and major bleeding. Secondary outcomes included risk of recurrence of the PE and intracranial hemorrhage.

Thrombolytic therapy was associated with lower all-cause mortality and with higher risk of bleeding. There was a 9.24% rate of major bleeding in the thrombolytic therapy cohort and a 3.42% rate in the anticoagulation cohort. Intracranial hemorrhage was greater in the thrombolytic therapy cohort (1.46% vs. 0.19%). Patients with intermediate risk PE had greater major bleeding rate (7.74% vs. 2.25%) and lower mortality (1.39% vs. 2.92%) with thrombolytics compared to anticoagulation. A net clinical benefit calculation (mortality benefit accounting for intracranial hemorrhage risk) was performed and demonstrated a net clinical benefit of 0.81% (95% CI, 0.65%-1.01%) for those patients who received thrombolytics versus other anticoagulation.

Bottom line: This study suggested a mortality benefit of thrombolytics overall, including those patients with intermediate risk PE.

Citation: Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014;311(23):2414-2421.