Pulmonary embolism: no clear role for tPA as a bolus.

Clinical bottom line (level 1b-)

  1. There was no clear difference in mortality, major bleeding or recurrent pulmonary embolism in patients that received bolus tPA compare with tPA over two hours.
Goldhaber et al: Chest 1994; 106: 718-724
Expires October 2003

The study

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

87 patients (aged mean 56 years, 53% 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
  • major internal bleeding in previous year
  • intracranial or intraspinal disease
  • operation or biopsy in preceding ten days (or open heart surgery within fourteen days)
  • major urologic bleed within a month
  • history or major bleeding diathesis or chronic bleeding disorder
  • occult blood in the stool
  • haematocrit <30%
  • platelet count <100, 000 mm ³
  • persistent blood pressure >180 mmHg systolic, or 110 mmHg diastolic
  • prothrombin time >16 seconds
  • nursing mothers or pregnancy
  • haemorrhagic retinopathy
  • concurrent condition considered to limit survival to less than one month


    • Note:
  • Patients were randomised 2:1.


    • Control Group: (n = 27, 27 analysed): tPA 100 mg over two hours
    Experimental Group: (n = 60, 60 analysed): tPA 0.6 mg/ kg/ 15 minutes (maximum 50 mg)
    All patients received warfarin. All patients had baseline v/q scan, and another at 20-28 hrs. Patients at angiography centres had baseline angiogram, and at two hrs. Patients at echocardiogram centres had baseline, and at three and 20-28 hrs.
    100% followed for 14 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death 14 days 1
    (3.70%)    		 5
    (8.33%)    		 -125%
    (-1735% to 72%)    		 -4.63%
    (-14.6% to 5.35%)    		 -22
    (NNT = 19 to infinity;
    NNH = 7 to infinity)
    non-fatal recurrent PE 14 days 1
    (3.70%)    		 1
    (1.67%)    		 55%
    (-593% to 97%)    		 2.04%
    (-5.79% to 9.86%)    		 49
    (NNT = 10 to infinity;
    NNH = 17 to infinity)
    major bleed 14 days 6
    (22.2%)    		 8
    (13.3%)    		 40%
    (-56% to 77%)    		 8.89%
    (-9.00% to 26.8%)    		 11
    (NNT = 4 to infinity;
    NNH = 11 to infinity)

  • There was no significant difference in the changes noted in imaging studies for either regimen.

    • Comments

    1. The study was too small to demonstrate small benefits of one dosing method over the other.

    Citation

    1. Goldhaber SZ, Agnelli G, Levine M: Reduced dose bolus alteplase vs conventional alteplase infusion for pulmonary embolism thrombolysis. An international multicenter randomized trial. Chest 1994; 106: 718-724
    Contributor: Chris Ball and Clare Wotton, October 2000
    Reviewer:

    Clinical Question.
    Patient pulmonary embolism
    Intervention or Exposure tPA bolus
    Comparison tPA over two hours
    Outcome death, recurrence, bleeding