"Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases"

Appraised by: Deb Bynum, MD

Date: September 11, 1997

Clinical Bottom Lines:

1. Overall there was no beneficial effect of 3 weeks of heparin prophylaxis on necropsy verified, hospital-aquired, fatal pulmonary embolism in nonsurgical patients over the age of 55.

2. There was no difference in overall mortality between patients who received heparin prophylaxis (5.3%) compared to control patients (5.6%, p value 0.39)

3. There was also no difference between rates of DVT and PE at necropsy between these groups: thromboembolism was found in 95 (49%) of the heparin treated patients and 93 (49.2%) of the control group; PE was found in 33 patients on heparin and 26 patients in the control group; clinically relevant fatal PE was found in 15 patients in the heparin group and 16 patients in the control group.

4. There was no difference in mortality between these groups in patients with underlying malignancies (24 % in the heparin group and 25.6 % in the control group).

5. There were slightly more serious bleeding events found at necropsy in heparin treated patients (n=14) vs control (n=6), but this was not statistically significant.

6. There were significantly more non-fatal PE’s in the control group vs the heparin group during the study (58 vs 29, p value .0026) as well as overall non-fatal thromboembolic events (116 in the control group, 70 in the heparin group, p=.0012).

The evidence: Prospective, randomised, controlled, unblinded study of 19751 consecutive patients aged 55 years or older admitted to the department of Infectious Diseases. 11693 total patients were randomised to receive low dose subcutaneous heparin prophylaxis (5776) or nothing (5917). The primary endpoint of the study was defined as necropsy verified, fatal, hospital aquired pulmonary embolism.

Comments:

1. Although there was no observed difference in mortality or necropsy proven thromboembolic events, the occurrence of fatal PE was significantly delayed in the heparin group -- this suggests that heparin does protect against thromboembolic events but that the effects are short-lived after discontinuation of the heparin.

2. The study was limited in that it was unblinded and by the fact that informed consent was not obtained until after randomization ( 695 patients, 12 %, originally assigned to heparin refused or for other reasons did not receive heparin). No consent was obtained for patients in the control group...mmm.

3. Patients were excluded from the study if they were judged to be mobile (n=872), have a significant risk of bleeding (n=603), or felt by their primary doctor to have a strong indication for heparin prophylaxis (n=365). Excluding patients because of a perceived greater need for prophylaxis may skew results, making the heparin arm look less favorable.

Source: Lancet 1996; 347: 1357-61.