Short-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of prospective studies investigating symptomatic outcomes.

BACKGROUND The prevalence of asymptomatic deep vein thrombosis diagnosed by venography after hip or knee replacement remains high despite 7 to 10 days of anticoagulant prophylaxis. However, the risk of symptomatic events in such patients is unclear. We performed a meta-analysis to provide reliable estimates of the risk of symptomatic venous thromboembolism occurring within 3 months of hip or knee replacement in patients who received short-duration (7-10 days) anticoagulant prophylaxis. METHODS The MEDLINE, EMBASE, and Cochrane databases were searched from January 1993 to March 2001, supplemented by a manual search of bibliographies and conference abstracts, to identify prospective studies of patients undergoing hip or knee replacement who received short-duration prophylaxis (ie, 7-10 days of fixed-dose low-molecular-weight heparin or adjusted-dose warfarin, with a target international normalized ratio of 2.0-3.0). Studies were classified as clinical outcome studies if the outcome was symptomatic venous thromboembolism or as venographic outcome studies if the outcome was asymptomatic deep vein thrombosis diagnosed after bilateral venography. RESULTS There were 4 clinical outcome studies with 6089 patients who had 3 months of follow-up, and 13 venographic outcome studies with 7080 patients who had venography 7 to 10 days after surgery. In clinical outcome studies, the 3-month incidence of nonfatal venous thromboembolism was 3.2% (95% confidence interval [CI], 2.0%-4.4%), and the 3-month incidence of fatal pulmonary embolism was 0.10% (95% CI, 0.02%-0.20%). The postprophylaxis incidence of nonfatal venous thromboembolism was 2.2% (95% CI, 1.4%-3.0%), and the incidence of fatal pulmonary embolism was 0.05% (95% CI, 0%-0.12%). The postprophylaxis incidence of symptomatic venous thromboembolism was higher after hip than after knee replacement (2.5% vs 1.4%; P=.02). In venographic outcome studies, the prevalence of deep vein thrombosis (total and proximal) was higher after knee than after hip replacement (total: 38.8% vs 16.4%; P<.001; proximal: 7.6% vs 3.8%; P<.001). CONCLUSIONS In patients who undergo hip or knee replacement and receive short-duration anticoagulant prophylaxis, symptomatic nonfatal venous thromboembolism will occur in about 1 of 32 patients and fatal pulmonary embolism will occur in about 1 of 1000 patients within 3 months of the surgery. Although the prevalence of asymptomatic deep vein thrombosis is more than 2-fold higher after knee replacement than after hip replacement 7 to 10 days after surgery, in the subsequent 3 months, symptomatic venous thromboembolism is more likely to occur after hip replacement.

[1]  J. Douketis,et al.  Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials , 2001, The Lancet.

[2]  J. Heit,et al.  Prevention of venous thromboembolism. , 2001, Clinics in geriatric medicine.

[3]  C. Colwell,et al.  Prevention of venous thromboembolism. , 1994, Chest.

[4]  A. Nicolaides,et al.  Prevention of venous thromboembolism. International Consensus Statement. Guidelines compiled in accordance with the scientific evidence. , 2001, International angiology : a journal of the International Union of Angiology.

[5]  J. Heit.  Low-molecular-weight heparin: the optimal duration of prophylaxis against postoperative venous thromboembolism after total hip or knee replacement. , 2001, Thrombosis research.

[6]  P. Romano,et al.  Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. , 2000, The New England journal of medicine.

[7]  C. Francis,et al.  Low-molecular-weight heparin prophylaxis using dalteparin Extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients : A double-blind, randomized comparison , 2000 .

[8]  C. Francis,et al.  Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients : A double-blind, randomized comparison , 2000 .

[9]  E. Goldwasser,et al.  A new transacting factor that modulates hypoxia-induced expression of the erythropoietin gene , 2000 .

[10]  B. Morrey,et al.  Ardeparin Sodium for Extended Out-of-Hospital Prophylaxis against Venous Thromboembolism after Total Hip or Knee Replacement , 2000, Annals of Internal Medicine.

[11]  I. Olkin,et al.  Meta-analysis of observational studies in epidemiology - A proposal for reporting , 2000 .

[12]  Eter,et al.  A COMPARISON OF RECOMBINANT HIRUDIN WITH A LOW-MOLECULAR-WEIGHT HEPARIN TO PREVENT THROMBOEMBOLIC COMPLICATIONS AFTER TOTAL HIP REPLACEMENT , 2000 .

[13]  C. Colwell,et al.  Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. , 1999, The Journal of bone and joint surgery. American volume.

[14]  D. D’Lima,et al.  Late deep venous thrombosis and delayed weightbearing after total hip arthroplasty. , 1999, Clinical orthopaedics and related research.

[15]  V. A. Skoutakis,et al.  A comparison of danaparoid and warfarin for prophylaxis against deep vein thrombosis after total hip replacement: The Danaparoid Hip Arthroplasty Investigators Group. , 1998, Orthopedics.

[16]  W. Bargar,et al.  Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. , 1998, Archives of internal medicine.

[17]  J. Hirsh,et al.  The Incidence of Symptomatic Venous Thromboembolism During and After Prophylaxis With Enoxaparin: A Multi-institutional Cohort Study of Patients Who Underwent Hip or Knee Arthroplasty , 1998 .

[18]  W. Harper,et al.  Mortality and fatal pulmonary embolism after primary total hip replacement - Results from a regional hip register , 1997 .

[19]  W. Harper,et al.  Mortality and fatal pulmonary embolism after primary total hip replacement. Results from a regional hip register. , 1997, The Journal of bone and joint surgery. British volume.

[20]  M. Gent,et al.  Ultrasonographic Screening before Hospital Discharge for Deep Venous Thrombosis after Arthroplasty: The Post-Arthroplasty Screening Study: A Randomized, Controlled Trial , 1997, Annals of Internal Medicine.

[21]  S. Totterman,et al.  Prevention of Deep-Vein Thrombosis after Total Hip Arthroplasty. Comparison of Warfarin and Dalteparin* , 1997, The Journal of bone and joint surgery. American volume.

[22]  G. Finerman,et al.  The Efficacy of Prophylaxis with Low-Dose Warfarin for Prevention of Pulmonary Embolism following Total Hip Arthroplasty* , 1997, The Journal of bone and joint surgery. American volume.

[23]  L. Pedell.  Enoxaparin as prophylaxis against thromboembolism after total hip replacement. , 1997, The New England journal of medicine.

[24]  A. Nicolaides.  Prevention of Venous Thromboembolism: International Consensus Statement , 1997 .

[25]  A. Nicolaides,et al.  Prevention of venous thromboembolism. International Consensus Statement (guidelines according to scientific evidence). , 1997, International angiology : a journal of the International Union of Angiology.

[26]  H. Arnesen,et al.  Prolonged Thromboprophylaxis Following Hip Replacement Surgery – Results of a Double-blind, Prospective, Randomised, Placebo-controlled Study with Dalteparin (Fragmin®) , 1997, Thrombosis and Haemostasis.

[27]  C. Ruckley,et al.  Still missing the boat with fatal pulmonary embolism , 1996, The British journal of surgery.

[28]  D. Bergqvist,et al.  Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. , 1996, The New England journal of medicine.

[29]  A. Planès,et al.  Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo , 1996, The Lancet.

[30]  G. Agnelli,et al.  Distribution and Occlusiveness of Thrombi in Patients with Surveillance Detected Deep Vein Thrombosis after Hip Surgery , 1996, Thrombosis and Haemostasis.

[31]  W. Geerts,et al.  Prevention of venous thromboembolism after knee arthroplasty. A randomized, double-blind trial comparing enoxaparin with warfarin. , 1996, Annals of internal medicine.

[32]  J. van der Meer,et al.  Subcutaneous Low-Molecular Weight Heparin or Oral Anticoagulants for the Prevention of Deep-Vein Thrombosis in Elective Hip and Knee Replacement? , 1995, Thrombosis and Haemostasis.

[33]  T. Sculco,et al.  Changes in circulatory indices of thrombosis and fibrinolysis during total knee arthroplasty performed under tourniquet. , 1995, The Journal of arthroplasty.

[34]  G. Bannister,et al.  Death and thromboembolic disease after total hip replacement. A series of 1162 cases with no routine chemical prophylaxis. , 1995, The Journal of bone and joint surgery. British volume.

[35]  S. Soimakallio,et al.  Prophylaxis for the prevention of venous thromboembolism after total knee arthroplasty. A comparison between unfractionated and low-molecular-weight heparin. , 1994, The Journal of bone and joint surgery. American volume.

[36]  G H Guyatt,et al.  Users' guides to the medical literature. VI. How to use an overview. Evidence-Based Medicine Working Group. , 1994, JAMA.

[37]  R. Blasier,et al.  Efficacy and Safety of Enoxaparin to Prevent Deep Venous Thrombosis after Hip Replacement Surgery , 1994, Annals of Internal Medicine.

[38]  G. Raskob,et al.  A Comparison of Subcutaneous Low-Molecular-Weight Heparin with Warfarin Sodium for Prophylaxis Against Deep-Vein Thrombosis After Hip or Knee Implantation , 1994 .

[39]  C. Colwell,et al.  Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. A clinical trial comparing efficacy and safety. Enoxaparin Clinical Trial Group. , 1994, The Journal of bone and joint surgery. American volume.

[40]  I. Pinder,et al.  The incidence of fatal pulmonary embolism after knee replacement with no prophylactic anticoagulation. , 1993, The Journal of bone and joint surgery. British volume.

[41]  I. Pinder,et al.  WITH NO PROPHYLACTIC ANTICOAGULATION , 1993 .

[42]  B. Morrey,et al.  Venous thromboembolism associated with hip and knee arthroplasty: current prophylactic practices and outcomes. , 1992, Mayo Clinic proceedings.

[43]  B Urquhart,et al.  Effects of epidural anesthesia on the incidence of deep-vein thrombosis after total knee arthroplasty. , 1991, The Journal of bone and joint surgery. American volume.

[44]  M. Prins,et al.  A Comparison of General Anesthesia and Regional Anesthesia as a Risk Factor for Deep Vein Thrombosis Following Hip Surgery: A Critical Review , 1990, Thrombosis and Haemostasis.

[45]  R. Pho,et al.  Femoral vein occlusion during hip arthroplasty. , 1990, Clinical orthopaedics and related research.

[46]  B. Eriksson,et al.  Phlebographic Findings in Venous Thrombosis following Total Hip Replacement , 1990, Acta radiologica.

[47]  F Mosteller,et al.  Some Statistical Methods for Combining Experimental Results , 1990, International Journal of Technology Assessment in Health Care.

[48]  K A L'Abbé,et al.  Meta-analysis in clinical research. , 1987, Annals of internal medicine.

[49]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[50]  A. Clarke.  Femoral vein thrombosis and total hip replacement. , 1977, British medical journal.

[51]  G. Stiris,et al.  The risk of deep-vein thrombosis after operations on a bloodless lower limb. A venographic study. , 1976, Injury.

[52]  V. Kakkar,et al.  Natural history of postoperative deep-vein thrombosis. , 1969, Lancet.