Pulmonary embolism: no clear role for thrombolysis with tPA.

Clinical bottom line (level 1b-)

  1. Patients with a pulmonary embolism who received tPA and heparin had improved right ventricular wall motion (NNT = 5 at 24 hours) , and less tricuspid regurgitation (NNT = 5 at 24 hours) compared with patients given heparin alone.
  2. There was no clear difference in the death rate or recurrence of pulmonary embolisms.
Goldhaber et al: Lancet 1993; 341: 507-511
Expires October 2003

The study

Unblinded ?concealed randomised trial with intention-to-treat
Setting: university hospital, USA

101 patients (aged mean 59 years, 51% female) pulmonary embolism confirmed by high probability ventilation-perfusion scan or pulmonary angiography within 24 hours

Excluded if
  • <18 years old
  • major internal bleed in last six months
  • intracranial or intraspinal disease
  • surgery/ biopsy in last ten days
  • blood pressure >200/110 mmHg
  • severe hepatic dysfunction
  • pregnant
  • active infective endocarditis
  • haemorrhagic retinopathy
  • expected survival less than one month


    • Control Group: (n = 55, 55 analysed): heparin 5000 units bolus dose, followed by 1000 units per hour titred so that aPTT 1.5-2.5
    Experimental Group: (n = 46, 46 analysed): tPA 100mg given over 2 hrs (50 mg per hour) and heparin
    All patients received warfarin. Echocardiogram was performed at 0, 3 and 24 hours after starting treatment. Ventilation-perfusion scan was performed at 0 and 24 hours: scored using segment occlusion chart by two radiologists.
    100% followed for 14 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    no improved right ventricular wall motion 24 hours 47
    (85.5%)    		 30
    (65.2%)    		 24%
    (3% to 40%)    		 20.2%
    (3.62% to 36.9%)    		 5
    (3 to 28)
    no improved tricuspid regurgitation 24 hours 47
    (85.5%)    		 30
    (65.2%)    		 24%
    (3% to 40%)    		 20.2%
    (3.62% to 36.9%)    		 5
    (3 to 28)
    death 14 days 2
    (3.64%)    		 0
    (0.00%)    		 100%
    (% to %)    		 3.64%
    (-1.31% to 8.58%)    		 28
    (NNT = 12 to infinity;
    NNH = 76 to infinity)
    nonfatal recurrent pulmonary embolism 14 days 3
    (5.45%)    		 0
    (0.00%)    		 100%
    (% to %)    		 5.45%
    (-0.55% to 11.5%)    		 18
    (NNT = 9 to infinity;
    NNH = 180 to infinity)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    increase in lung perfusion (%) 14.6
    ()     		1.5
    ()     		13
    (12 to 15)

  • Deaths were due to recurrent pulmonary embolism.

    • Comments

    1. The study is very small and uses secondary endpoints with short follow-up. It is not large enough to show any small benefit or harm for thrombolysis.

    Citation

    1. Goldhaber SZ, Haire WD, Feldstein ML, et al: Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet 1993; 341: 507-511
    Contributor: Chris Ball and Clare Wotton, October 2000
    Reviewer:

    Clinical Question.
    Patient pulmonary embolism
    Intervention or Exposure tPA
    Comparison heparin
    Outcome death, recurrence, ventricular wall motion