Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage: A Meta-Analysis
What are the mortality benefits and bleeding risks associated with thrombolytic therapy compared with anticoagulation in acute pulmonary embolism (PE), including the subset of hemodynamically stable patients with right ventricular (RV) dysfunction (intermediate-risk PE)?
Eligible studies for analysis were randomized clinical trials comparing thrombolytic therapy versus anticoagulant therapy in PE patients. Sixteen trials comprising 2,115 individuals were identified. Eight trials comprising 1,775 patients specified inclusion of patients with intermediate-risk PE. Two reviewers independently extracted trial-level data including number of patients, patient characteristics, duration of follow-up, and outcomes. The primary outcomes were all-cause mortality and major bleeding. Secondary outcomes were risk of recurrent embolism and intracranial hemorrhage (ICH). Peto odds ratio (OR) estimates and associated 95% confidence intervals (CIs) were calculated using a fixed-effects model.
Use of thrombolytics was associated with lower all-cause mortality (OR, 0.53; 95% CI, 0.32-0.88; 2.17% [23/1,061] vs. 3.89% [41/1,054] with anticoagulants; number needed to treat [NNT] = 59) and greater risks of major bleeding (OR, 2.73; 95% CI, 1.91-3.91; 9.24% [98/1,061] vs. 3.42% [36/1,054]; number needed to harm [NNH] = 18) and ICH (OR, 4.63; 95% CI, 1.78-12.04; 1.46% [15/1,024] vs. 0.19% [2/1,019]; NNH = 78). Major bleeding was not significantly increased in patients 65 years and younger (OR, 1.25; 95% CI, 0.50-3.14). Thrombolysis was associated with a lower risk of recurrent PE (OR, 0.40; 95% CI, 0.22-0.74; 1.17% [12/1,024] vs. 3.04% [31/1,019]; NNT = 54). In intermediate-risk PE trials, thrombolysis was associated with lower mortality (OR, 0.48; 95% CI, 0.25-0.92) and more major bleeding events (OR, 3.19; 95% CI, 2.07-4.92).
The authors concluded that among patients with PE, including those who were hemodynamically stable with RV dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH.
This systematic review and meta-analysis demonstrate lower associated mortality with thrombolytic use in PE. Furthermore, results suggest potential mortality benefit with thrombolytic therapy in patients with hemodynamically stable PE with RV dysfunction in contemporary clinical practice. This is the first analysis of thrombolysis in PE that has sufficient statistical power to detect associations with a meaningful mortality reduction. However, the optimism regarding this clinical advantage must be tempered by the finding of significantly increased risk of major bleeding and ICH associated with thrombolytic therapy, particularly for patients older than 65 years. If the results of this analysis are confirmed in randomized clinical trials, there may be a shift in the treatment of appropriately selected patients with intermediate-risk PE using thrombolytics.
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