Pulmonary embolism: anticoagulation reduced mortality and recurrence.

Clinical bottom line (level 1b)

  1. A quarter of patients with a pulmonary embolism who were not anticoagulated died. A third had a recurrence.
  2. Patients with a pulmonary embolism need to be anticoagulated - it reduced death (NNT = 4 at 12 months) , and recurrent PEs (NNT = 4 at 12 months) .
Barritt and Jordan: Lancet 1960; 1: 1309-1312
Expires October 2005

The study

Unblinded ?concealed randomised trial with intention-to-treat
Setting: teaching hospital, UK

35 patients (aged ?, ?% male) first episode of clinically diagnosed pulmonary embolism

Excluded if
  • recent surgery
  • history strongly suggestive of a pulmonary embolism


    • Control Group: (n = 19, 19 analysed): no anticoagulation
    Experimental Group: (n = 16, 16 analysed): heparin iv 10, 000 units every six hours for six doses, and nicoumalone for 14 days, so PT was 2-3 times normal. Some patients had 28 days of nicoumalone if unable to mobilise.

    100% followed for 12-24 months

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death from pulmonary embolism 12 months 5
    (26.3%)    		 0
    (0.0%)    		 100%
    (% to %)    		 26.3%
    (6.52% to 46.1%)    		 4
    (2 to 15)
    recurrence of pulmonary embolism 12 months 5
    (26.3%)    		 0
    (0.0%)    		 100%
    (% to %)    		 26.3%
    (6.52% to 46.1%)    		 4
    (2 to 15)

    Comments

    1. The trial was terminated early due to the number of deaths.
    2. Anticoagulants were contraindicated if recent surgery, or patient had history suggestive of a PE (ie avoided in higher risk patients - ?overestimated anticoagulation benefit).
    3. Diagnosis was subjective - clinicians poor at picking up PE. Some patients entered 12 days after diagnosis. How confident can we be that all patients had PEs?
    4. The study is unlikely to be repeated - unethical. Estimates may be overoptimistic, but still significant.
    5. Anticoagulation was for a short time - does the increased risk of death continue for longer than two weeks? i.e. does long-term anticoagulation reduce mortality? It would seem not according to this study - no further deaths occurred in the anticoagulated group after the 14 day period - but there are very small numbers in the trial. Certainly long-term anticoagulation reduces recurrent PEs and DVTs, but studies looking at anticoagulation duration have been too small to detect significant differences in mortality.

    Citation

    1. Barritt DW, and Jordan SC: Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet 1960; 1: 1309-1312
    Contributor: Chris Ball and Clare Wotton, October 2000
    Reviewer:

    Clinical Question.
    Patient pulmonary embolism
    Intervention or Exposure anticoagulation
    Comparison no anticoagulation
    Outcome death and recurrence