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Thrombolytics for PE

Thrombolytics for PE. Stephen Akers, MD. Heparin for PE Barritt & Jordan 1960. 35 pt’s with clinical PE Acute RV failure Pulmonary Infarction. Barritt, Jordan Lancet 1960:1:1309. Barritt & Jordan 1960. 19 pt’s no treatment 16 pt’s IV heparin (36 hours) & coumadin (2 weeks .

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Thrombolytics for PE

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  1. Thrombolytics for PE Stephen Akers, MD

  2. Heparin for PE Barritt & Jordan 1960 • 35 pt’s with clinical PE • Acute RV failure • Pulmonary Infarction Barritt, Jordan Lancet 1960:1:1309

  3. Barritt & Jordan 1960 • 19 pt’s no treatment • 16 pt’s IV heparin (36 hours) & coumadin (2 weeks

  4. Barritt & Jordan 1960 • 5/19 untreated pt’s died of PE • 0/16 treated pt’s died a • p=.04

  5. Barritt & Jordan 1960 • 5/19 untreated pt’s non fatal recurrence • 0/16 treated pt’s non fatal recurrence

  6. Barritt & Jordan 1960 • Death and Recurrence • No Tx 10/19 • Tx 0/16 • p=.0005

  7. Barritt & Jordan 1960 • “Every patient who received the first injection of heparin survived.”

  8. Barritt & Jordan 1960 • Tx 38 additional pt’s • Death 0/38 • Recurrence 1/38

  9. Barritt & Jordan 1960 • Death, Recur in all (73) • No Tx 10/19 • Tx 1/54 • P=0.0000014!!

  10. Barritt & Jordan 1960 • No objective studies • Groups unmatched • Massive PE • Statistical methods

  11. Natural Hx • Hypoten >50% occlus • Shock > 80% occlus • Death < 1 hour

  12. Resolution PE • Mechanical Change • In vivo fibrinolysis • Partial within days • Complete within months

  13. Urokinase PE Trial (UPET) • 160 patients • Heparin 78- shock 5 • Urokinase 82- shock 9 JAMA Dec 21, 1970 Vol 214:2163

  14. UPET Inclusion • Compatible Clin Picture • PE within 5 days • PA gram segmental defect or greater

  15. UPET Protocol • 2,000 unit load • 2,000 unit/lb/hour • 12 hour infusion • Heparin

  16. UPET End Points • Pulm A gram • Right heart cath • V/Q scan

  17. UPET End Points • Before treatment • 6 to 18 hours post treatment

  18. UPET V/Q Scan • Five times first two weeks • Months 3, 6, 12

  19. Thrombolysis • Improved clot lysis • Improved hemodynm • Improved perfusion • Increased bleeding

  20. Bleeding • Heparin 27% • Uro/Strep 45% • Cut down sites for cath • One CNS bleed

  21. UPET no difference • Symptoms • Recurrence 15% v. 19% • Perfusion after day 5 • Mortality (6 vs. 5)

  22. Urokinase-Streptokinase PE Trial (USPET) • 59 urokin 12 hours • 54 urokin 24 hours • 54 streptokin 24 hours JAMA Sept 16, 1974 Vol 229:1606

  23. USPET no difference • Clot lysis • Hemodynamics • Reperfusion • Recurrence • Mortality

  24. Thrombolytics • Faster clot lysis • More bleeding • No improvement in clinical outcome

  25. DLCO Thrombolytics • Sub group UPET/USPET • Heparin 21 pt’s • Uro/Strepto 19 pt’s Sharma N Engl J Med 1980; 303:842

  26. Diffusing Capacity • Hep 2 wks 19 (69%) • Uro/Str 2 wks 22 (85%) • Hep 1 year 20 ((72%) • Uro/Str 1 year 24 (93%)

  27. DLCO Thrombolytics • Total diffusing capacity • Membrane diffusion • Pul/cap blood volume

  28. Membrane Diffusion • Hep 2 wks 52 • Uro/str 2 wks 47 • Hep 1 year 49 • Uro/Str 1 year 50

  29. Pulmonary-Capillary Blood Volume • Hep 2 weeks 30 • Uro/strep 2 weeks 45 • Hep 1 year 28 • Uro/Strep 1 year 49

  30. Thrombolytics DLCO • More complete resolution of pulm microthrombi • Clincal implications unclear

  31. Urokinase v. tPA • 45 Pt’s angio doc PE • tPA 22; 23 urokin • Clot lysis @ 2 hours • Perfusion @ 24 hours Goldhaber, et al Lancet 6 August 1988 293-298

  32. Urokinase v. tPA • tPA all pt’s full dose • Uro 9 pt’s stopped • bleeding 8 • allergic rx 1

  33. Urokinase v. TPA • Clot lysis @ 2 hours • tPA 82% • Uro 48% • p=0.008

  34. Urokinase v. TPA Perfusion @ baseline & 24 hours • tPA 59% to 71% • Uro 58% to 70% • no difference

  35. Urokinase v. TPA • Conclusions • tPA quicker lysis • tPA safer

  36. Additional tPA studies • Better lysis, less bleeding • Improved hemodyn • IV equiv to intrapulm

  37. tPA Levine Study • 68 pt’s PE on heparin • 33 tPA vs. 25 placebo • Q scan 24 hr, 7 days Levine, et al Chest 1990;98:1473-79

  38. tPA Levine Study • Improv perf @ 24 h • tPA 10% v placeb 5% • No improv perf @ 7 d • tPA 16% v placeb 11%

  39. tPA Goldhaber Study • 46 tPA v 55 heparin • Echo • Perfusion • Recurrence • Mortality Goldhaber, et al Lancet1993; 341:507-11

  40. tPA v Heparin • Improved echo • tPA 39% v heparin 17% • Improv’d perfusion • tPA 15% v heparin 2%

  41. tPA v Heparin • tPA • No death, no recurr • Heparin • 2 death, 3 recurr • p=0.06

  42. RV Dysfun in PE • Increased death • Despite absence of hypotension, shock Goldhaber, et al Lancet 1999;353:1386-8 Kasper, et al J AmColl Cardiol 1997;30:1165-71

  43. RV Dysfunction • Normal blood pressure • RV Dys 9% mortal • N’l RV 0.5% mortal

  44. Improvement in RV Dysfunction • t PA improves RV dysfunction acutely • RV function similar at one week hep or TPA

  45. tPA v Heparin Submassive PE • Hemo stable PE plus • RV dysfunction echo • Pul HTN echo or cath • RV strain EKG Konstantinides, et al NEJM 2002:347:1143

  46. Primary End Points • Primary • Death, escalation of Tx • Secondary • Recur PE, bleed, CVA

  47. Escalation of Tx • Wors’ng Sx’s (dyspnea) • Wors’ng respir failure • Wors’ng echo, cath • Hypotension

  48. Escalation of Tx • Catecholamines • Intubation, CPR • Embolectomy • Sec’dary thrombolysis

  49. Konstantinides, et al NEJM 2002:347:1143

  50. Konstantinides, et al NEJM 2002:347:1143

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