Characteristics of included studies comparing thrombolysis to anticoagulation
| Reference (year) . | Type of PE . | N . | Thrombolytic regimen . | Comparator . | Inclusion/exclusion criteria* . | Primary outcome . | Follow-up, d . | Definition of RVD . | Major bleeding definitions . |
|---|---|---|---|---|---|---|---|---|---|
| 10 (1970) | Unclear | 160 | Urokinase 2000 CTA units per lb in 10 min, followed by 2000 CTA units per lb per h for 12 h | Heparin | Acute PE ≤5 d, age ≥18 y, ≥1 segmental artery occlusion | Not specified | 14 | NA | Hct drop >10 points, transfusion ≥2 PRBCs |
| 11 (1974) | Unclear | 30 | Streptokinase 600 000 IU bolus, then 100 000 IU/h for 72 h | Heparin | Acute or progressive life-threatening PE | Changes in angiographic scores and hemodynamic measurements after 72 h | 3 | NA | NA |
| 12 (1978) | Unclear | 25 | Streptokinase 250 000 IU bolus, then 100 000 IU/h for 72 h | Heparin | Acute PE ≤5 d, age <70 y, PE >1 lobar artery | Angiographic score changes after 72 h of treatment | 10 | NA | NA |
| 13 (1979) | Unclear | 31 | Streptokinase 250 000 IU bolus, then 100 000 IU/h for 18-72 h | Heparin | Acute PE, no other specific criteria | Not specified | 7 | NA | NA |
| 14 (1988) | Unclear | 30 | Urokinase 800 000 IU for 3 d (2 400 000 IU) or urokinase 3 300 000 IU for 12 h | Heparin | Acute PE ≤7 d, age <72 y, normal coagulation assays | Not specified | 7 | NA | NA |
| 15 (1990) | Unclear, but excluded hypotensive patients | 58 | Alteplase 0.6 mg/kg over 2 min | Heparin | Acute PE ≤14 d, not in shock or hypotensive | Improvement in perfusion of >50% from baseline scan | 10 | NA | ICH, RP bleed, transfusion ≥2 PRBCs, Hgb drop >2g/dL |
| 16 (1990) | Unclear, but excluded hypotensive patients | 13 | Alteplase 40-80 mg over 40-90 min | Heparin | Acute PE ≤7 d, not in shock, occlusion of 1 lobar or ≥2 segmental arteries | Not specified | 7 | NA | NA |
| 17 (1992) | Unclear, but excluded hypotensive patients | 36 | Alteplase 100 mg over 2 h | Heparin | Acute PE ≤10 d, age 18-80 y, vascular obstruction >30%, Miller index score >11, not in shock | Change in pulmonary angiographic index | 30 | NA | ICH, require transfusion |
| 18 (1993) | Stable | 101 | Alteplase 100 mg over 2 h | Heparin | Acute PE ≤14 d | RV wall motion improvement at 24 h | 14 | NA | ICH, require surgery |
| 19 (1995) | Unstable | 8 | Streptokinase 1 500 000 IU over 1 h | Heparin | Acute PE ≤14 d, age ≥15 y, massive PE (>9 obstructed segments) with or without shock or <9 segments with RVD and/or extensive DVT | Not specified | Not specified (1-3) | NA | NA |
| 20 (2002) | Stable | 256 | Alteplase 100 mg over 2 h | Heparin | Acute PE ≤4 d, age <80 y, RVD or pulmonary HTN or EKG of RV strain | In-hospital death or clinical deterioration | 30 | RV enlargement with loss of inspiratory collapse of inferior vena cava | ICH, fatal, Hgb drop >4g/dL |
| 21 (2009) | Stable | 58 | Tenecteplase IV 30-50 mg | Heparin | Acute PE ≤10 d, age 18-85 y, RVD by echo or CT, normal BP | Reduction of RVD by echo at 24 h | 30 | RV/left ventricular end-diastolic dimension ratio >1 apical view or >0.7 parasternal long axis | ICH, fatal, require transfusion or interventions |
| 22 (2011) | Stable | 72 | Alteplase 100 mg over 2 h | Heparin | Acute PE ≤6h, RVD by echo, +d-dimer, normal BP, hypoxia, or specified EKG changes | Reduction of RVD by echo at follow-ups | 180 | RV hypokinesis, RV dilatation, pulmonary HTN, paradoxical septal movement | ICH, fatal, require transfusion or interventions |
| 23 (2013) | Stable | 121 | Alteplase 0.5mg/kg up to 50 mg over 2h | Heparin or enoxaparin | Acute PE ≤10 d, >2 lobar or main artery, ≥2 new symptoms | Pulmonary HTN and recurrent PE | 840 | RV enlargement or hypokinesis, or troponin and BNP elevation | NA |
| 24 (2014) | Stable | 83 | Tenecteplase IV 30-50 mg (weight-based) | Weight-based enoxaparin or dalteparin | Acute PE ≤24 h, age >17 y, normal BP with RVD | VTE recurrence or treatment-related adverse outcomes, and poor functional capacity within 90 d | 5 | Hypokinesis on echo, elevated troponin, BNP >90 pg/mL, or N-terminal-ProBNP >900 pg/mL | ICH, fatal, require interventions or transfusion, Hgb drop >2 g/dL |
| 25 (2014) | Stable | 1005 | Tenecteplase IV 30-50 mg (weight-based) | Heparin | Acute PE ≤15 d, RVD by echo or CT, myocardial injury by elevated troponin | Death and hemodynamic collapse within 7 d | 7 (when analysis done), followed up to 30 | Confirmed by echo or CT criteria | ICH, life threatening, require transfusion |
| Reference (year) . | Type of PE . | N . | Thrombolytic regimen . | Comparator . | Inclusion/exclusion criteria* . | Primary outcome . | Follow-up, d . | Definition of RVD . | Major bleeding definitions . |
|---|---|---|---|---|---|---|---|---|---|
| 10 (1970) | Unclear | 160 | Urokinase 2000 CTA units per lb in 10 min, followed by 2000 CTA units per lb per h for 12 h | Heparin | Acute PE ≤5 d, age ≥18 y, ≥1 segmental artery occlusion | Not specified | 14 | NA | Hct drop >10 points, transfusion ≥2 PRBCs |
| 11 (1974) | Unclear | 30 | Streptokinase 600 000 IU bolus, then 100 000 IU/h for 72 h | Heparin | Acute or progressive life-threatening PE | Changes in angiographic scores and hemodynamic measurements after 72 h | 3 | NA | NA |
| 12 (1978) | Unclear | 25 | Streptokinase 250 000 IU bolus, then 100 000 IU/h for 72 h | Heparin | Acute PE ≤5 d, age <70 y, PE >1 lobar artery | Angiographic score changes after 72 h of treatment | 10 | NA | NA |
| 13 (1979) | Unclear | 31 | Streptokinase 250 000 IU bolus, then 100 000 IU/h for 18-72 h | Heparin | Acute PE, no other specific criteria | Not specified | 7 | NA | NA |
| 14 (1988) | Unclear | 30 | Urokinase 800 000 IU for 3 d (2 400 000 IU) or urokinase 3 300 000 IU for 12 h | Heparin | Acute PE ≤7 d, age <72 y, normal coagulation assays | Not specified | 7 | NA | NA |
| 15 (1990) | Unclear, but excluded hypotensive patients | 58 | Alteplase 0.6 mg/kg over 2 min | Heparin | Acute PE ≤14 d, not in shock or hypotensive | Improvement in perfusion of >50% from baseline scan | 10 | NA | ICH, RP bleed, transfusion ≥2 PRBCs, Hgb drop >2g/dL |
| 16 (1990) | Unclear, but excluded hypotensive patients | 13 | Alteplase 40-80 mg over 40-90 min | Heparin | Acute PE ≤7 d, not in shock, occlusion of 1 lobar or ≥2 segmental arteries | Not specified | 7 | NA | NA |
| 17 (1992) | Unclear, but excluded hypotensive patients | 36 | Alteplase 100 mg over 2 h | Heparin | Acute PE ≤10 d, age 18-80 y, vascular obstruction >30%, Miller index score >11, not in shock | Change in pulmonary angiographic index | 30 | NA | ICH, require transfusion |
| 18 (1993) | Stable | 101 | Alteplase 100 mg over 2 h | Heparin | Acute PE ≤14 d | RV wall motion improvement at 24 h | 14 | NA | ICH, require surgery |
| 19 (1995) | Unstable | 8 | Streptokinase 1 500 000 IU over 1 h | Heparin | Acute PE ≤14 d, age ≥15 y, massive PE (>9 obstructed segments) with or without shock or <9 segments with RVD and/or extensive DVT | Not specified | Not specified (1-3) | NA | NA |
| 20 (2002) | Stable | 256 | Alteplase 100 mg over 2 h | Heparin | Acute PE ≤4 d, age <80 y, RVD or pulmonary HTN or EKG of RV strain | In-hospital death or clinical deterioration | 30 | RV enlargement with loss of inspiratory collapse of inferior vena cava | ICH, fatal, Hgb drop >4g/dL |
| 21 (2009) | Stable | 58 | Tenecteplase IV 30-50 mg | Heparin | Acute PE ≤10 d, age 18-85 y, RVD by echo or CT, normal BP | Reduction of RVD by echo at 24 h | 30 | RV/left ventricular end-diastolic dimension ratio >1 apical view or >0.7 parasternal long axis | ICH, fatal, require transfusion or interventions |
| 22 (2011) | Stable | 72 | Alteplase 100 mg over 2 h | Heparin | Acute PE ≤6h, RVD by echo, +d-dimer, normal BP, hypoxia, or specified EKG changes | Reduction of RVD by echo at follow-ups | 180 | RV hypokinesis, RV dilatation, pulmonary HTN, paradoxical septal movement | ICH, fatal, require transfusion or interventions |
| 23 (2013) | Stable | 121 | Alteplase 0.5mg/kg up to 50 mg over 2h | Heparin or enoxaparin | Acute PE ≤10 d, >2 lobar or main artery, ≥2 new symptoms | Pulmonary HTN and recurrent PE | 840 | RV enlargement or hypokinesis, or troponin and BNP elevation | NA |
| 24 (2014) | Stable | 83 | Tenecteplase IV 30-50 mg (weight-based) | Weight-based enoxaparin or dalteparin | Acute PE ≤24 h, age >17 y, normal BP with RVD | VTE recurrence or treatment-related adverse outcomes, and poor functional capacity within 90 d | 5 | Hypokinesis on echo, elevated troponin, BNP >90 pg/mL, or N-terminal-ProBNP >900 pg/mL | ICH, fatal, require interventions or transfusion, Hgb drop >2 g/dL |
| 25 (2014) | Stable | 1005 | Tenecteplase IV 30-50 mg (weight-based) | Heparin | Acute PE ≤15 d, RVD by echo or CT, myocardial injury by elevated troponin | Death and hemodynamic collapse within 7 d | 7 (when analysis done), followed up to 30 | Confirmed by echo or CT criteria | ICH, life threatening, require transfusion |
BNP, brain natriuretic peptide; BP, blood pressure; CT, computed tomography; CTA, National Heart Institute Committee on Thrombolytic Agents unit of urokinase activity; echo, echocardiogram; EKG, electrocardiogram; Hct, hematocrit; Hgb, hemoglobin; HTN, hypertension; ICH, intracranial hemorrhage; NA, not available; RP, retroperitoneal; PRBCs, packed red blood cells; RV, right ventricular; RVD, RV dysfunction; VTE, venous thromboembolism.
All studies excluded patients with high risk of bleeding, including active bleeding, recent surgery, thrombocytopenia, and severe hypertension (systolic blood pressure >200 mm Hg).