Timing of Perioperative Pharmacologic Thromboprophylaxis Initiation and its Effect on Venous Thromboembolism and Bleeding Outcomes: A Systematic Review and Meta-Analysis

Background: Perioperative thromboprophylaxis guidelines offer conflicting recommendations on when to start thromboprophylaxis. As a result, there is considerable variation in clinical practice, which can lead to worse patient outcomes. The objective of this study was to evaluate the association between the start time of perioperative thromboprophylaxis with venous thromboembolism (VTE) and bleeding outcomes.

Study design: Embase, Medline, and CENTRAL (Cochrane Central Register of Controlled Trials) databases were searched on October 23, 2020. Randomized controlled trials that evaluated VTE and/or bleeding among groups receiving the initial dose of pharmacologic thromboprophylaxis at different times preoperatively, intraoperatively, or postoperatively were included. Only trials that randomized patients to the same medication among groups were eligible. Studies on any type of operation were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The Cochrane Collaboration risk of bias tool was used. The review was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42019142079). The outcomes of interest were VTE and bleeding. Prespecified subgroup analyses of studies including orthopaedic and nonorthopaedic operations were performed.

Results: A total of 22 trials (n = 17,124 patients) met eligibility criteria. Pooled results showed a nonstatistically significant decrease in the rate of VTE with preoperative initiation of thromboprophylaxis compared with postoperative initiation (risk ratio 0.77; 95% CI, 0.55 to 1.08; I² = 0%, n = 1,933). There was also a nonstatistically significant increase in the rate of bleeding with preoperative compared with postoperative initiation (risk ratio 1.17; 95% CI, 0.94 to 1.46; I² = 35%, n = 2,752). Risk of bias was moderate. Heterogeneity between studies was low (I² = 0% to 35%).

Conclusions: This meta-analysis found a nonstatistically significant decrease in the rate of VTE and an increase in the rate of bleeding when thromboprophylaxis was initiated preoperatively compared with postoperatively.