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Russell D. Hull, MBBS, MSc; Rollin F. Brant, PhD; Graham F. Pineo, MD; Paul D. Stein, MD; Gary E. Raskob, MSc; Karen A. Valentine, MD, PhD

Arch Intern Med. 1999;159:137-141.

Background  Although preoperative and postoperative initiation of prophylaxis for deep vein thrombosis (DVT) with low-molecular-weight heparin (LMWH) are effective, the relative effectiveness and safety of these approaches is unknown. In the absence of a published definitive level 1 trial addressing this question, a meta-analysis is appropriate.

Objective  To report a meta-analysis comparing preoperative with postoperative initiation of prophylaxis of DVT in patients undergoing elective hip replacement.

Methods  Relevant trials were identified, and potential biases in the meta-analysis were minimized by analyzing all rigorously performed randomized trials that met all of the following criteria for conduct of the trial: (1) double-blind design, (2) objective documentation of the frequencies of DVT by ascending contrast venography, (3) venography performed before or at the time of discharge from the hospital, (4) initiation of the same LMWH preoperatively or postoperatively in dosages shown to be effective, (5) compliance with the criteria for a level 1 trial, and (6) objective documentation of major and minor bleeding according to strict criteria.

Results  Treatment with LMWH initiated preoperatively was associated with a DVT frequency of 10.0% compared with a frequency of 15.3% when the LMWH was initiated postoperatively (P=.02, Fisher exact test). Major bleeding was less frequent in patients receiving preoperatively initiated LMWH than in patients receiving postoperatively initiated LMWH (0.9%, vs 3.5%; P=.01, Fisher exact test).

Conclusions  Our findings support the need for a randomized comparison of preoperative and postoperative initiation of pharmacological prophylaxis of DVT. Such a trial would resolve the divergent practices for DVT prophylaxis between Europe and the North American countries, the United States and Canada, and would affect the treatment for thousands of patients on both continents.

From the Thrombosis Research Unit, Foothills Hospital, University of Calgary, Calgary, Alberta (Drs Hull, Brant, Pineo, and Valentine); the Cardiac Wellness Unit, Henry Ford Hospital, Detroit, Mich (Dr Stein); and the Departments of Medicine and Biostatistics and Epidemiology, University of Oklahoma, Oklahoma City (Dr Raskob).

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