Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review

Ann Intern Med. 2001 Nov 20;135(10):858-69. doi: 10.7326/0003-4819-135-10-200111200-00006.


Purpose: Evidence-based medicine guidelines based on venographic end points recommend in-hospital prophylaxis with low-molecular-weight heparin (LMWH) in patients having elective hip surgery. Emerging data suggest that out-of-hospital use may offer additional protection; however, uncertainty remains about the risk-benefit ratio. To provide clinicians with a practical pathway for translating clinical research into practice, we systematically reviewed trials comparing extended out-of-hospital LMWH prophylaxis versus placebo.

Data sources: Studies were identified by 1) searching PubMed, MEDLINE, and the Cochrane Library Database for reports published from January 1976 to May 2001; 2) reviewing references from retrieved articles; 3) scanning abstracts from conference proceedings; and 4) contacting pharmaceutical companies and investigators of the original reports.

Study selection: Randomized, controlled trials comparing extended out-of-hospital prophylaxis with LMWH versus placebo in patients having elective hip arthroplasty.

Data extraction: Two reviewers extracted data independently. Reviewers evaluated study quality by using a validated four-item instrument.

Data synthesis: Six of seven original articles met the defined inclusion criteria. The included studies were double-blind trials that used proper randomization procedures. Compared with placebo, extended out-of-hospital prophylaxis decreased the frequency of all episodes of deep venous thrombosis (placebo rate, 150 of 666 patients [22.5%]; relative risk, 0.41 [95% CI, 0.32 to 0.54; P < 0.001]), proximal venous thrombosis (placebo rate, 76 of 678 patients [11.2%]; relative risk, 0.31 [CI, 0.20 to 0.47; P < 0.001]), and symptomatic venous thromboembolism (placebo rate, 36 of 862 patients [4.2%]; relative risk, 0.36 [CI, 0.20 to 0.67; P = 0.001]). Major bleeding was rare, occurring in only one patient in the placebo group.

Conclusions: Extended LMWH prophylaxis showed consistent effectiveness and safety in the trials (regardless of study variations in clinical practice and length of hospital stay) for venographic deep venous thrombosis and symptomatic venous thromboembolism. The aggregate findings support the need for extended out-of-hospital prophylaxis in patients undergoing hip arthroplasty surgery.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Aftercare*
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Arthroplasty, Replacement, Hip / adverse effects*
  • Double-Blind Method
  • Hemorrhage / chemically induced
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Sensitivity and Specificity
  • Time Factors
  • Venous Thrombosis / prevention & control*


  • Anticoagulants
  • Heparin, Low-Molecular-Weight