Efficacy and safety of dabigatran for venous thrombosis prophylaxis after knee replacement surgery in Thai patients: a prospective non-randomized controlled trial

Intiyanaravut, Tawan; Thongpulsawasdi, Nimit; Sinthuvanich, Napol; Songtaweesap, Sasikarn

doi:10.1515/abm-2019-0064

Abstract

Background

Dabigatran, a direct oral anticoagulant, has been approved for the prevention of venous thromboembolism (VTE) after orthopedic surgery in many countries. The efficacy and safety of this agent were most studied in Western countries.

Objective

To assess the efficacy and safety of dabigatran in preventing venous thromboembolic diseases after total knee arthroplasty (TKA) in Asian patients.

Methods

We conducted a prospective nonrandomized controlled study in Thai patients undergoing TKA. Thirty-two patients received 220 mg of dabigatran once daily for 14 days as thromboprophylaxis and 32 patients in the control group received none. The primary efficacy outcome was deep vein thrombosis (DVT), which was identified by color Doppler ultrasonography and/or diagnosed pulmonary embolism (PE). The primary safety outcomes were major bleeding and clinically relevant nonmajor bleeding events.

Results

There were no DVTs or PEs diagnosed in either group. The difference in the composite incidence of major and clinically relevant nonmajor bleedings between the dabigatran and control groups did not reach significant (6.2% vs. 0%, P = 0.15).

Conclusion

Dabigatran might have no clear benefit for the prevention of VTE after TKA in Thai patients. We do not recommend the routine use of dabigatran as a chemical thromboprophylaxis after TKA in Thai patients. To determine the safety profile, further study with larger sample sizes is required.

References

Stulberg BN, Insall JN, Williams GW, Ghelman B. Deep-vein thrombosis following total knee replacement. An analysis of six hundred and thirty-eight arthroplasties. J Bone Joint Surg Am. 1984; 66:194–201.
Search in Google Scholar Back to article
Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al. Prevention of VTE in orthopedic surgery patients: antithrombotic therapy and prevention of thrombosis, 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141:e278S–e325S.
Search in Google Scholar Back to article
Bin Abd Razak HR, Soon AT, Dhanaraj ID, Tan AH. Incidence of clinically significant venous thromboembolic events in Asian patients undergoing total knee arthroplasty without anticoagulation. J Arthroplasty. 2012; 27:1128–32.
Search in Google Scholar Back to article
Kim YH, Kim JS. Incidence and natural history of deep-vein thrombosis after total knee arthroplasty. A prospective, randomised study. J Bone Joint Surg Br. 2002; 84:566–70.
Search in Google Scholar Back to article
Ko PS, Chan WF, Siu TH, Khoo J, Wu WC, Lam JJ. Deep venous thrombosis after total hip or knee arthroplasty in a low-risk Chinese population. J Arthroplasty. 2003; 18:174–9.
Search in Google Scholar Back to article
Leizorovicz A, Committee SVSS (SMART Venography Study Steering Committee). Epidemiology of post-operative venous thromboembolism in Asian patients. Results of the SMART venography study. Haematologica. 2007; 92:1194–200.
Search in Google Scholar Back to article
Won MH, Lee GW, Lee TJ, Moon KH. Prevalence and risk factors of thromboembolism after joint arthroplasty without chemical thromboprophylaxis in an Asian population. J Arthroplasty. 2011; 26:1106–11.
Search in Google Scholar Back to article
Friedman RJ, Dahl OE, Rosencher N, Caprini JA, Kurth AA, Francis CW, et al. Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: a pooled analysis of three trials. Thromb Res. 2010; 126:175–82.
Search in Google Scholar Back to article
Fuji T, Fuijita S, Ujihira T, Sato T. Dabigatran etexilate prevents venous thromboembolism after total knee arthroplasty in Japanese patients with a safety profile comparable to placebo. J Arthroplasty. 2010; 25:1267–74.
Search in Google Scholar Back to article
The European Agency for the Evaluation of Medicinal Products, Committee for Medicinal Products for Human Use (CHMP). Guideline on clinical investigation of medicinal products for prophylaxis of high intra- and post-operative venous thromboembolic risk. [online] 2012. [cited 2012 Mar 15]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicinal-products-prophylaxis-high-intra-post-operative-venous_en.pdf.
Search in Google Scholar Back to article
Blanchard J, Meuwly JY, Leyvraz PF, Miron MJ, Bounameaux H, Hoffmeyer P, et al. Prevention of deep-vein thrombosis after total knee replacement. Randomised comparison between a low-molecular-weight heparin (nadroparin) and mechanical prophylaxis with a foot-pump system. J Bone Joint Surg Br. 1999; 81:654–9.
Search in Google Scholar Back to article
Nathan S, Aleem MA, Thiagarajan P, Das De S. The incidence of proximal deep vein thrombosis following total knee arthroplasty in an Asian population: a Doppler ultrasound study. J Orthop Surg (Hong Kong). 2003; 11:184–9.
Search in Google Scholar Back to article
Sudo A, Sano T, Horikawa K, Yamakawa T, Shi D, Uchida A. The incidence of deep vein thrombosis after hip and knee arthroplasties in Japanese patients: a prospective study. J Orthop Surg (Hong Kong). 2003; 11:174–7.
Search in Google Scholar Back to article
Cohen AT, Asia-Pacific Thrombosis Advisory Board. Asia-Pacific Thrombosis Advisory Board consensus paper on prevention of venous thromboembolism after major orthopaedic surgery. Thromb Haemost. 2010; 104:919–30.
Search in Google Scholar Back to article
Rostagno C. New oral anticoagulants in prophylaxis of venous thromboembolic disease in major orthopedic surgery. Cardiovasc Hematol Disord Drug Targets. 2016; 15:204–9.
Search in Google Scholar Back to article
Intiyanaravut T, Thongpulsawasdi N, Sinthuvanich N, Teavirat S, Kunopart M. Enoxaparin versus no anticoagulation prophylaxis after total knee arthroplasty in Thai patients: a randomized controlled trial. J Med Assoc Thai. 2017; 100:42–9.
Search in Google Scholar Back to article
Barnes RW, Nix ML, Barnes CL, Lavender RC, Golden WE, Harmon BH, et al. Perioperative asymptomatic venous thrombosis: role of duplex scanning versus venography. J Vasc Surg. 1989; 9:251–60.
Search in Google Scholar Back to article
Vaitkus PT, Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Goldhaber SZ, et al. Mortality rates and risk factors for asymptomatic deep vein thrombosis in medical patients. Thromb Haemost. 2005; 93:76–9.
Search in Google Scholar Back to article
Grady-Benson JC, Oishi CS, Hanson PB, Colwell CW Jr, Otis SM, Walker RH. Postoperative surveillance for deep venous thrombosis with duplex ultrasonography after total knee arthroplasty. J Bone Joint Surg Am. 1994; 76:1649–57.
Search in Google Scholar Back to article