Pulmonary embolism: urokinase increased bleeding without reducing death or recurrent PE.

Clinical bottom line (level 1b)

  1. Patients with pulmonary embolism who received urokinase compared with heparin were not clearly less likely to die or have a recurrent PE.
  2. Patients given urokinase were at increased risk of bleeding (NNH = 5 at 14 days) , particularly severely (NNH = 8 at 14 days) .
Sherry et al: Circulation 1973; 17 (suppl2): -
Expires October 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: acute hospitals, USA

160 patients (aged median 50 years, 58% male) pulmonary embolism (diagnosed on pulmonary angiography) within last five days

Excluded if
  • aged <18
  • contraindication to thrombolysis: severe systemic hypertension with grade III or IV retinopathy, stroke or neurosurgery within two months, presence of actively bleeding GI ulcer; blood coagulation abnormality
  • surgical intervention (venous ligation or pulmonary embolectomy) anticipated
  • severe renal or hepatic disease
  • pregnancy or within ten days post-partum


    • Note:
  • Patients were stratified for shock and size of pulmonary embolism before randomisation.


    • Control Group: (n = 78, 78 analysed): heparin ~150 units/kg bolus followed by ~20 units/kg for 12 hours
    Experimental Group: (n = 82, 82 analysed): urokinase ~4000 units/kg bolus followed by ~4000 units/kg infusion for 12 hours
    All patients had iv heparin for another five days, followed by anticoagulation (adjusted so PT was 2 to 2.5 times control).
    100% followed for 14 days
    Outcome notes:
    • recurrent pulmonary embolism : new perfusion defect 10% or more

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death 14 days 7
    (8.97%)    		 6
    (7.32%)    		 18%
    (-132% to 71%)    		 1.66%
    (-6.83% to 10.1%)    		 60
    (NNT = 15 to infinity;
    NNH = 10 to infinity)
    recurrent pulmonary embolism 14 days 5
    (6.41%)    		 5
    (6.10%)    		 5%
    (-216% to 71%)    		 0.31%
    (-7.20% to 7.82%)    		 320
    (NNT = 14 to infinity;
    NNH = 13 to infinity)
    overt bleeding 14 days 21
    (26.9%)    		 37
    (45.1%)    		 -68%
    (-159% to -8%)    		 -18.2%
    (-32.8% to -3.61%)    		 -5
    (-28 to -3)
    severe bleeding 14 days 11
    (14.1%)    		 22
    (26.8%)    		 -90%
    (-266% to 1%)    		 -12.7%
    (-25.0% to -0.41%)    		 -8
    (-240 to -4)

    Citation

    1. Sherry S, et al: Urokinase-Pulmonary embolism trial. Circulation 1973; 17 (suppl2): -
    Contributor: Chris Ball and Clare Wotton, October 2000
    Reviewer:

    Clinical Question.
    Patient pulmonary embolism
    Intervention or Exposure urokinase
    Comparison heparin
    Outcome recurrence, death, bleeding