Efficacy of Rivaroxaban for thromboprophylaxis after Knee Arthroscopy (ERIKA)A phase II, multicentre, double-blind, placebo-controlled randomised study Financial support: Bayer SpA provided the study drugs and covered the insurance costs.
12 February 2016
Accepted after major revision: 05 April 2016
09 March 2018 (online)
Without thromboprophylaxis, knee arthroscopy (KA) carries a low to moderate risk of venous thromboembolism. Over 5 million arthroscopies are performed worldwide yearly. It was our study objective to assess the efficacy and safety of rivaroxaban for thromboprophylaxis after therapeutic KA. Patients undergoing KA in nine Italian teaching or community hospitals were allocated to once-daily rivaroxaban (10 mg) or placebo for seven days in a phase II, multicentre, double-blind, placebo-controlled randomised trial. The primary efficacy outcome was a composite of all-cause death, symptomatic thromboembolism and asymptomatic proximal DVT at three months; major bleeding represented the primary safety outcome. All patients underwent whole-leg ultrasonography at day 7(+1), or earlier if symptomatic. A total of 241 patients were randomised (122 rivaroxaban, 119 placebo), and 234 completed the study. The primary efficacy outcome occurred in 1/120 of the rivaroxaban group and in 7/114 of the placebo group (0.8% vs 6.1%, respectively, p=0.03; absolute risk difference, −5.3%, 95% CI, −11.4 to −0.8; crude relative risk 0.14, 95% CI, 0.02 to 0.83; number-needed-to-treat=19). No major bleedings were observed. We found no association between different arthroscopic procedures and thrombotic events. Small sample size, high exclusion rate, and low number of anterior cruciate ligament reconstruction procedures are the main limitations of our study. In conclusion, a seven-day course of 10-mg rivaroxaban may be safely employed for thromboprophylaxis after KA. Whether prophylaxis after KA should be given to all patients, or to selected “high-risk” subjects, remains to be determined. A larger trial to verify our preliminary results is warranted.
- 1 Hoppener MR, Ettema HB, Henny CP. et al. Low incidence of deep vein thrombosis after knee arthroscopy without thromboprophylaxis A prospective cohort study of 335 patients. Acta Orthop Scand 2006; 77: 767-771.
- 2 Graham WC, Flanigan DC.. Venous thromboembolism following arthroscopic knee surgery: a current concepts review of incidence, prophylaxis and preoperative risk assessment. Sports Med 2014; 44: 331-343.
- 3 Demers C, Marcoux S, Ginsberg JS. et al. Incidence of venographically proved deep vein thrombosis after knee arthroscopy. Arch Intern Med 1998; 158: 47-50.
- 4 Dahl OE, Gudmundsen TE, Haukeland L.. Late occurring clinical deep vein thrombosis in joint operated patients. Acta Orthop Scand 2000; 71: 47-50.
- 5 Jareguito JW, Greenwald AE, Wilcox JF. et al. The incidence of deep venous thrombosis after arthroscopic knee surgery. Am J Sports Med 1999; 27: 707-710.
- 6 Delis KT, Hunt N, Strachan RK, Nicolaides AN.. Incidence, natural history and risk factors of deep vein thrombosis in elective knee arthroscopy. Thromb Haemost 2001; 86: 817-821.
- 7 van Adrichem RA, Nelissen RGHH, Schipper IB. et al. Risk of venous thrombosis after arthroscopy of the knee: results from a large population based case-control study. J Thromb Haemost 2015; 13: 1441-1448.
- 8 Wirth T, Schneider B, Misselwitz F. et al. Prevention of venous thromboembolism after knee arthroscopy with low molecular weight heparin (Reviparin): results of a randomised controlled trial. Arthroscopy 2001; 17: 393-399.
- 9 Schippinger G, Wirnsberger GH, Obernosterer A. et al. Thromboembolic complications after arthroscopic knee surgery. Incidence and risk factors in 101 patients. Acta Orthop Scand 1998; 69: 144-146.
- 10 Michot M, Conen D, Holtz D. et al. Prevention of deep-vein thrombosis in ambulatory arthroscopic knee surgery: a randomised trial of prophylaxis with low-molecular weight heparin. Arthroscopy 2002; 18: 257-263.
- 11 Camporese G, Bernardi E, Prandoni P. et al. Low-molecular-weight heparin versus graduated compression stockings for prevention of venous thromboembolism after knee arthroscopy. A randomised trial. Ann Intern Med 2008; 149: 73-82.
- 12 Geerts WH, Bergqvist D, Pineo GF. et al. Prevention of Venous Thromboembolism. The 8th ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2008; 133: 381S-453S.
- 13 Ageno W, Dentali F, Imberti D.. A survey of thrombosis prophylaxis use in patients undergoing arthroscopic surgery. J Thromb Haemost 2004; 2: 1901-1902.
- 14 Turpie AG, Lassen MR, Eriksson BI. et al. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost 2011; 105: 444-453.
- 15 Prins MH, Lensing AW, Bauersachs R. et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomised studies. Thromb J 2013; 11: 21.
- 16 Patel MR, Mahaffey KW, Garg J. et al. ROCKET AF Investigators. N Engl J Med 2011; 365: 883-891.
- 17 Muñoa L, Gonzalez AB, Diaz de Rada P. et al. Rivaroxaban is as efficient and safe as bemiparin as thromboprophylaxis in knee arthroscopy. Musculoskelet Surg 2014; 98: 21-25.
- 18 Harris PA, Taylor R, Thielke R. et al. Research electronic data capture (RED- Cap) – A meta data-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42: 377-381.
- 19 Committee for Proprietary Medicinal Products. Points to consider on clinical investigation of medicinal products for prophylaxis of intra- and post-operative venous thromboembolic risk. London: European Agency for the Evaluation of Medicinal Products; 2000. Available at http://www.emea.europa.eu/pdfs/human/ewp/070798en.pdf Accessed on May 20, 2008.
- 20 Schulman S, Kearon C. on behalf of the subcommittee on control of anticoagulation of the scientific and standardisation committee of the International Society On Thrombosis and haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-694.
- 21 Torbicki A, Perrier A, Konstantinides S. et al. ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008; 29: 2276-2315.
- 22 Cogo A, Lensing AW, Koopman MM. et al. Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. Br Med J 1998; 316: 17-20.
- 23 Ilahi OA, Reddy J, Ahmad I.. Deep venous thrombosis after knee arthroscopy: a meta-analysis. Arthroscopy 2005; 21: 727-730.
- 24 Ramos J, Perrotta C, Badariotti G. et al. Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy. Cochrane Database Syst Rev 2008; 2: CD005259.
- 25 Fleiss J. L.. Statistical Methods for Rates and Proportions. New York: John Wiley & Sons Inc.; 1981: 24-26.
- 26 Chernick M. R., Liu C. Y.. The saw-toothed behavior of power versus sample size and software solutions: single binomial proportion using exact methods. Am Statistician 2002; 56: 149-155.
- 27 Miettinen OS, Nurminen M.. Comparative analysis of two rates. Statistics Med 1985; 4: 231-236.
- 28 Newcombe R.. Interval estimation for the difference between independent proportions. Statistics Med 1998; 17: 873-890.
- 29 Koopman PAR. Confidence limits for the ratio of two binomial proportions. Biometrics 1984; 40: 513-517.
- 30 Gart JJ, Nam J.. Approximate interval estimation for the difference in binomial parameters: correction for skewness and extension to multiple tables. Biometrics 1990; 46: 637-643.
- 31 Gart JJ, Nam J.. Approximate interval estimation for the ratio of binomial parameters: a review and correction for skewness. Biometrics 1988; 44: 323-338.
- 32 Kahn SR, Ducruet T, Lamping DL. et al. Prospective evaluation of health-related quality of life in patients with deep venous thrombosis. Arch Intern Med 2005; 165: 1173-1178.
- 33 Turpie AG, Lassen MR, Davidson BL. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009; 373: 1673-1680.
- 34 Prandoni P, Noventa F, Ghirarduzzi A. et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007; 92: 199-205.
- 35 Sun Y, Chen D, Xu Z. et al. Incidence of symptomatic and asymptomatic venous thromboembolism after elective knee arthroscopic surgery: a retrospective study with routinely applied venography. Arthroscopy 2014; 30: 818-822.
- 36 Lassen MR, Ageno W, Borris LC. et al. for the RECORD3 Investigators. Rivaroxaban versus Enoxaparin for Thromboprophylaxis after Total Knee Arthro-plasty. N Engl J Med 2008; 358: 2776-2786.
- 37 Goodacre S, Sampson F, Thomas S. et al. Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis. BMC Medical Imaging 2005; 5: 6.
- 38 Struijk-Mulder MC, Ettema HB, Verheyen CC. et al. Deep vein thrombosis after arthroscopic anterior cruciate ligament reconstruction: a prospective cohort study of 100 patients. Arthroscopy 2013; 29: 1211-1216.