title: Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis.
abstract: OBJECTIVE
  Thrombolytic therapy may be beneficial in the treatment of some patients with pulmonary embolism. To date, no analysis has had adequate statistical power to determine whether thrombolytic therapy is associated with improved survival, compared with conventional anticoagulation.
  
  
  OBJECTIVE
  To determine mortality benefits and bleeding risks associated with thrombolytic therapy compared with anticoagulation in acute pulmonary embolism, including the subset of hemodynamically stable patients with right ventricular dysfunction (intermediate-risk pulmonary embolism).
  
  
  METHODS
  PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from inception through April 10, 2014.
  
  
  METHODS
  Eligible studies were randomized clinical trials comparing thrombolytic therapy vs anticoagulant therapy in pulmonary embolism patients. Sixteen trials comprising 2115 individuals were identified. Eight trials comprising 1775 patients specified inclusion of patients with intermediate-risk pulmonary embolism.
  
  
  METHODS
  Two reviewers independently extracted trial-level data including number of patients, patient characteristics, duration of follow-up, and outcomes.
  
  
  METHODS
  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% CIs were calculated using a fixed-effects model.
  
  
  RESULTS
  Use of thrombolytics was associated with lower all-cause mortality (OR, 0.53; 95% CI, 0.32-0.88; 2.17% [23/1061] vs 3.89% [41/1054] 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% [98/1061] vs 3.42% [36/1054]; number needed to harm [NNH] = 18) and ICH (OR, 4.63; 95% CI, 1.78-12.04; 1.46% [15/1024] vs 0.19% [2/1019]; 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 pulmonary embolism (OR, 0.40; 95% CI, 0.22-0.74; 1.17% [12/1024] vs 3.04% [31/1019]; NNT = 54). In intermediate-risk pulmonary embolism 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).
  
  
  CONCLUSIONS
  Among patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH. However, findings may not apply to patients with pulmonary embolism who are hemodynamically stable without right ventricular dysfunction.
authors.affiliation: Division of Cardiology, St Luke's-Roosevelt Hospital Center of the Mount Sinai Health System, New York, New York.
authors.forename: Saurav
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Division of Pulmonology and Critical Care, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Anasua
authors.initials: A
authors.lastname: Chakraborty
authors.affiliation: Institute for Heart, Vascular, and Stroke Care, Massachusetts General Hospital, Boston.
authors.forename: Ido
authors.initials: I
authors.lastname: Weinberg
authors.affiliation: Division of Cardiovascular Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
authors.forename: Mitul
authors.initials: M
authors.lastname: Kadakia
authors.affiliation: Division of Cardiovascular Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wilensky
authors.affiliation: Division of Cardiology, Texas Tech University, El Paso.
authors.forename: Partha
authors.initials: P
authors.lastname: Sardar
authors.affiliation: Division of Cardiology, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Dharam J
authors.initials: DJ
authors.lastname: Kumbhani
authors.affiliation: Division of Cardiology, Texas Tech University, El Paso.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukherjee
authors.affiliation: Institute for Heart, Vascular, and Stroke Care, Massachusetts General Hospital, Boston.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jaff
authors.affiliation: Division of Cardiovascular Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
authors.forename: Jay
authors.initials: J
authors.lastname: Giri
mesh_terms: D000208:Acute Disease; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced* / Q000453:epidemiology; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D012306:Risk; D015912:Thrombolytic Therapy / Q000009:adverse effects; D016896:Treatment Outcome; D018497:Ventricular Dysfunction, Right
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents