1. Acute Venous Pulmonary Embolism Restore cardiopulmonary hemodynamics Avoid recurrence Avoid chronic thromboembolic pulmonary hypertension Restore cardiopulmonary hemodynamics Avoid recurrence Avoid chronic thromboembolic pulmonary hypertension Goals of Therapy …with their associated morbidity and mortality

2. Pulmonary Embolism Chronic Thromboembolic Pulmonary Hypertension After First Episode of PE 6 months 1.0% 6 months 1.0% 1 year 3.1% 1 year 3.1% 2 years 3.8% 2 years 3.8% CTPH Pengo V, et al NEJM 2004;350:2257 Pengo V, et al NEJM 2004;350:2257

3. Pulmonary Embolism Recommendations for Anticoagulation Similar to DVT

4. Rapid improvement of arteriogram and lung scans (P<.05) Reduced PA and R arterial pressure (P<.05) No difference in overall mortality (study not designed to detect mortality difference) Less mortality with massive PE Rapid improvement of arteriogram and lung scans (P<.05) Reduced PA and R arterial pressure (P<.05) No difference in overall mortality (study not designed to detect mortality difference) Less mortality with massive PE NIH Trials: Early Results Circulation 1973; 39: S II -1 JAMA1974; 229:1606-13 Circulation 1973; 39: S II -1 JAMA1974; 229:1606-13 Thrombolytic Rx for PE

5. Improved pulmonary cap blood vol (P<.001) Improved O 2 diffusing capacity (P<.05) Reduced PA pressure @ rest and exercise (P<.05) Reduced PVR @ rest and exercise (P<.05) Less recurrent DVT and PE (P<.05) Less CHF (NYHA II-IV) (P<.05) Improved pulmonary cap blood vol (P<.001) Improved O 2 diffusing capacity (P<.05) Reduced PA pressure @ rest and exercise (P<.05) Reduced PVR @ rest and exercise (P<.05) Less recurrent DVT and PE (P<.05) Less CHF (NYHA II-IV) (P<.05) NIH Trials: Long-Term Results Circulation 1973; 39: S II -1 JAMA1974; 229:1606-13 Circulation 1973; 39: S II -1 JAMA1974; 229:1606-13

6. Jerjes-Sanchez C, et al J Thromb Thrombolyis 1995; 2:227 Jerjes-Sanchez C, et al J Thromb Thrombolyis 1995; 2:227 100% (4/4) 0% (0/4) Mortality* Heparin Alone SK + Heparin *Ethics committee terminated trial! Massive Pulmonary Embolism Lytic Rx vs. Anticoagulation Randomized Trial

7. Hemodynamic Outcome 0.06 9% 0 0 Recurrent PE (14 days) 0.0001 1.5% 14.6% Improved Pulm. Per. 0.01 26 cm 2 23.8 cm 2 End diastolic area 17% 2% Worse 0.005 17% 39% Improved Right Vent. Fct. (24 hrs) P-value Heparin rt-PA Goldhaber SZ Lancet 1993 Goldhaber SZ Lancet 1993 Lytic Rx for PE: Randomized Trial

8. Lytic Rx vs. Anticoagulation Multicenter registry Thrombolytic Rx vs. anticoagulation 30-day mortality lower in patients receiving lytic Rx (4.7 vs. 11.1, P=0.016) Primary lysis was only independent predictor of survival (multivariate analysis) Multicenter registry Thrombolytic Rx vs. anticoagulation 30-day mortality lower in patients receiving lytic Rx (4.7 vs. 11.1, P=0.016) Primary lysis was only independent predictor of survival (multivariate analysis) Konstantinides S, et al Circulation 1997 Konstantinides S, et al Circulation 1997 Pulmonary Embolism

9. Pre-RxPre-Rx

10. Pre-RxPre-Rx