Low-Molecular-Weight Heparin versus Compression Stockings for Thromboprophylaxis after Knee Arthroscopy

A Randomized Trial

15 July 2008 | Volume 149 Issue 2 | Pages 73-82

Background: Knee arthroscopy, the most common orthopedic operation worldwide, carries a definite risk for deep venous thrombosis; however, postsurgical thromboprophylaxis is not routinely recommended.

Objective: To evaluate whether low-molecular-weight heparin (LMWH) better prevents deep venous thrombosis and does not cause more complications than graduated compression stockings in adults having knee arthroscopy.

Design: Assessor-blind, randomized, controlled trial.

Setting: The Department of Knee Surgery, Abano Terme Clinic, Abano Terme (knee surgery, random assignment, and bleeding event survey), and the Unit of Angiology, University Hospital of Padua, Padua (efficacy outcomes evaluation, follow-up, data management, and analysis), Italy.

Patients: 1761 consecutive patients undergoing knee arthroscopy between March 2002 and January 2006.

Intervention: Patients were randomly assigned to wear full-length graduated compression stocking for 7 days (660 patients) or to receive a once-daily subcutaneous injection of LMWH (nadroparin, 3800 anti-Xa IU) for 7 days (657 patients) or 14 days (444 patients). The data and safety monitoring board prematurely stopped the 14-day heparin group after the second interim analysis.

Measurements: Combined incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality (primary efficacy end point) and combined incidence of major and clinically relevant bleeding events (primary safety end point). All patients had bilateral whole-leg ultrasonography at the end of the allocated prophylactic regimen or earlier if indicated. All patients with normal findings were followed for 3 months, and none was lost to follow-up.

Results: The 3-month cumulative incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality was 3.2% (21 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, 2.3 percentage points [95% CI, 0.7 to 4.0 percentage points]; P = 0.005), and 0.9% (4 of 444 patients) in the prematurely stopped 14-day LMWH group. The cumulative incidence of major or clinically relevant bleeding events was 0.3% (2 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, –0.6 percentage point [CI, –1.5 to 0.2 percentage points]), and 0.5% (2 of 444 patients) in the 14-day LMWH group.

Limitations: The study was not double-blind or double-dummy. Almost half of the events making up the composite outcome measure were distal deep venous thromboses. Stockings were used instead of placebo because of local prophylaxis policies.

Conclusion: In patients undergoing knee arthroscopy, prophylactic LMWH for 1 week reduced a composite end point of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality more than did graduated compression stockings.

Editors' Notes Context Many experts do not recommend thromboprophylaxis after knee arthroscopy. Contribution In this trial, 1761 adults who had knee arthroscopy were randomly assigned to receive daily low-molecular-weight heparin (LMWH) or to wear a full-length graduated compression stocking on the operated leg for 1 week. Fewer than 1% of the patients in either group had important postsurgical bleeding complications. During a 3-month follow-up, fewer cases of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and death occurred in patients who received LMWH than in those who wore stockings (0.9% vs. 3.2%). Caution Many outcomes were distal deep venous thromboses. Implication Postsurgical prophylactic LMWH for 1 week may prevent some thromboses after knee arthroscopy. —The Editors

 

Author and Article Information

From the University Hospital of Padua, Padua; Hospital of Conegliano Veneto, Conegliano; Ferrara Day Surgery, Ferrara; and the Abano Terme Clinic, Abano Terme, Italy.

International Standard Randomized Controlled Trial Number: ISRCTN75056741.

Acknowledgment: The authors thank Dr. Sabrina Perazzolo and Mr. Manuele Torelli for the creation of the database and data collection, Dr. Viviana Gialain for bibliographic search and for translating 2 papers from German to Italian, and Ms. Loretta Tasinato for the organization and planning of the visits of all the study patients. The authors also thank all the study patients, without whom this study would not have been possible.

Potential Financial Conflicts of Interest: None disclosed.

Reproducible Research Statement: Study protocol: Available by request from Dr. Camporese (e-mail, giuseppe.camporese{at}sanita.padova.it). Statistical code and data set: Not available.

Requests for Single Reprints: Giuseppe Camporese, MD, Unit of Angiology, University Hospital of Padua, Via Giustiniani 2,35128 Padua, Italy; e-mail, giuseppe.camporese{at}sanita.padova.it.

Current Author Addresses: Drs. Camporese, Verlato, Salmistraro, Cordova, Franz, and Andreozzi: Unit of Angiology, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy.

Dr. Bernardi: Department of Emergency and Accident Medicine, Hospital of Conegliano, Via Brigata Possagno 4, 31015 Conegliano (TV), Italy

Drs. Prandoni and Simioni: Department of Medical and Surgical Sciences, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy.

Dr. Noventa: Department of Clinical and Experimental Medicine, Clinical Epidemiology Group, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy.

Drs. Ntita, Frangos, and Rossi: Department of Knee Surgery, Abano Terme Clinic, Piazza Colombo 1, Abano Terme, Italy.

Dr. Zucchetta: Unit of Nuclear Medicine, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy.

Dr. Kontothanassis: Italian Phlebologic Institute at Ferrara Day Surgery, Via Verga 17, 44100 Ferrara, Italy.

Author Contributions: Conception and design: G. Camporese, E. Bernardi.

Analysis and interpretation of the data: G. Camporese, E. Bernardi, F. Noventa, F. Verlato.

Drafting of the article: G. Camporese, E. Bernardi, P. Prandoni, F. Noventa, F. Verlato.

Critical revision of the article for important intellectual content: G. Camporese, E. Bernardi, P. Prandoni, F. Noventa, F. Verlato, P. Simioni, G.M. Andreozzi.

Final approval of the article: G. Camporese, E. Bernardi, P. Prandoni, F. Noventa, F. Verlato, P. Simioni, K. Ntita, G. Salmistraro, C. Frangos, F. Rossi, R. Cordova, F. Franz, P. Zucchetta, D. Kontothanassis, G.M. Andreozzi.

Provision of study materials or patients: G. Camporese, K. Ntita, G. Salmistraro, C. Frangos, F. Rossi, R. Cordova, F. Franz, P. Zucchetta, D. Kontothanassis.

Statistical expertise: E. Bernardi, F. Noventa.

Collection and assembly of data: G. Camporese, E. Bernardi, F. Verlato, K. Ntita, G. Salmistraro, C. Frangos, F. Rossi, R. Cordova, F. Franz, P. Zucchetta, D. Kontothanassis.

^* For additional KANT study investigators, see the Appendix.

Read all Rapid Responses

Low-Molecular-Weight Heparin Versus Compression Stockings for Thromboprophylaxis

William Geerts

Annals Online, 7 Aug 2008 [Full text]

Author's Response: Low-Molecular-Weight Heparin versus Compression Stockings

Giuseppe Camporese, et al.

Annals Online, 27 Aug 2008 [Full text]