Pulmonary embolism: no clear advantage between tPA and urokinase.

Clinical bottom line (level 1b)

  1. There was no clear difference in major bleeding or changes in imaging studies in patients that received tPA compared with bolus urokinase.
Goldhaber et al: Journal of the American College of Cardiology 1992; 20 (1): 24-30
Expires October 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 28 hospitals in USA, Canada, Italy

90 patients (aged mean 59 years, 59% male) signs or symptoms of pulmonary embolism confirmed by high probability ventilation-perfusion scan or pulmonary angiogram within 14 days of onset

Excluded if
  • aged <18 years
  • major internal bleeding within previous six months
  • intracranial disease
  • operation or organ biopsy in past ten days
  • occult blood on stool examination
  • haematocrit <30%
  • severe uncontrolled hypertension
  • severe impairment of hepatic or renal function
  • pregnancy or lactation
  • inability to tolerate initial diagnostic pulmonary angiographic investigation


    • Control Group: (n = 46, 45 analysed): urokinase 1 million U over 10 min, followed by 2 million U over 110 min
    Experimental Group: (n = 44, 42 analysed): tPA 100 mg over two hours
    All patients received warfarin.
    97% followed for 14 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    no angiographic improvement 2 hours 15
    (33.3%)    		 9
    (21.4%)    		 36%
    (-31% to 68%)    		 11.9%
    (-6.63% to 30.4%)    		 8
    (NNT = 3 to infinity;
    NNH = 15 to infinity)
    major bleed 14 days 1
    (2.22%)    		 2
    (4.76%)    		 -114%
    (-2177% to 80%)    		 -2.54%
    (-10.3% to 5.21%)    		 -39
    (NNT = 19 to infinity;
    NNH = 10 to infinity)

  • Patients had baseline angiogram, and one at two hours. They also had baseline v/q scan and at 24 hours. Assessed by six blinded investigators. No significant difference was noted on v/q scan between the two groups.

    • Comments

    1. Advantage of thrombolysis over supportive therapy has not been clearly demonstrated.
    2. The study was too small to demonstrate any small benefits of one dosing method over the other. It is unclear how angiographic changes relate to patient outcomes.

    Citation

    1. Goldhaber SZ, Kessler CM, Heit JA, et al: Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial. Journal of the American College of Cardiology 1992; 20 (1): 24-30
    Contributor: Chris Ball and Clare Wotton, October 2000
    Reviewer:

    Clinical Question.
    Patient pulmonary embolism
    Intervention or Exposure tPA
    Comparison urokinase
    Outcome major bleeding, changes in imaging studies