Efficacy and safety of dabigatran in prevention of venous thromboembolism in patients undergoing major orthopedic surgeries: a review


  • Varsha Narayanan Lupin Medical Services and Research, BKC, Mumbai, Maharashtra, India
  • Amit Bhargava Lupin Medical Services and Research, BKC, Mumbai, Maharashtra, India




Dabigatran, Thrombin, Direct oral anticoagulants, Total hip and knee replacement, THR, Anticoagulants, Venous thromboembolism, Deep vein thrombosis, Pulmonary embolism


Thromboprophylaxis with anticoagulants can significantly reduce the risk of patients developing symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) and VTE related mortality post major orthopedic surgeries like total hip and knee replacement surgeries. Dabigatran, a directly acting oral anticoagulant (DOAC) and direct thrombin inhibitor, is an available option for VTE prophylaxis having comparable efficacy to low molecular weight heparins (LMWH), other DOACs and Warfarin, once daily dosing, and comparable safety and bleeding risk to both LMWH and Aspirin. Dabigatran is currently the only DOAC with an available and marketed reversing agent. A review of Dabigatran’s clinical efficacy and safety is presented here. Therefore, Dabigatran represents a balanced thromboprophylaxis option for VTE prevention in patients undergoing major orthopedic surgeries.


Author Biography

Varsha Narayanan, Lupin Medical Services and Research, BKC, Mumbai, Maharashtra, India

DGM Medical


Kakkar KA, Rushton-Smith S.K. Incidence of Venous Thromboembolism in Orthopedic Surgery. Thromboembolism Orthopedic Surg. 2013. DOI 10.1007/978-1-4471-4336-9_2

Caprini JA. Update on Risk Factors for Venous Thromboembolism. CME series jointly sponsored by the Elsevier Office of Continuing Medical Education (EOCME) and Excerpta Medica, Inc. Am J Med. 2005.

Flevas DA, Megaloikonomos PD, Dimopoulos L, Mitsiokapa E, Koulouvaris P, Mavrogenis AF.. Thromboembolism prophylaxis in orthopedics: an update. EFORT Open Rev. 2018;3:136-48.

Wang KL, Yap ES, Gotto S, Zhang S, Siu CW, Chiang CE. The diagnosis and treatment of venous thromboembolism in Asian patients. Thrombosis J. 2018;16:4.

Cohen AT, Tapson VF, Bergmann JF, Goldhaber SZ, Kakkar AK, Deslandes B, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet. 2008;371:387–94.

Mont MA, Jacobs JJ. AAOS clinical practice guideline: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg. 2011;19(12):777-8.

Ytter YF. 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(2):278–325.

Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133:381-453.

Scottish Intercollegiate Guidelines Network (SIGN). Prevention and management of venous thromboembolism. SIGN publication no. 122. Edinburgh: SIGN; 2010. 2015.

Nutescu EA, Shapiro NL, Ibrahim S, West P. Warfarin and its interactions with foods, herbs and other dietary Supplements. Expert Opin Drug Saf. 2006;5(3):433-51.

Narayanan S. Multifunctional role of thrombin. Ann Clin Lab Sci. 1999;29(4):275-80.

Lee C J, Ansell JE. Direct Thrombin Inhibitors. Br J Clin Pharmacol. 2011;72(4):581–92.

Bogatkevich GS, Bradley AL, Silver RM. Dabigatran, a direct thrombin inhibitor, blocks differentiation of normal fibroblasts to a myofibroblast phenotype and demonstrates anti-fibrotic effects on scleroderma lung fibroblasts. Arthritis Rheum. 2009;60(11):3455–64.

Ganetsky M, Babu KM, Salhanick SD, Brown RS, Boyer EW. Dabigatran: Review of Pharmacology and Management of Bleeding Complications of This Novel Oral Anticoagulant. J Med Toxicol. 2011;7:281–7.

Shulman S, Majeed A. A Benefit-Risk Assessment of Dabigatran in the Prevention of Venous Thromboembolism in Orthopaedic Surgery. Drug Saf. 2011;34 (6):449-63.

PRADAXA: USFDA Full prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s028lbl.pdf. Accessed on 3 June 2018.

Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van-Dijk CN, Frostick SP et al. Oral Dabigatran etexilate vs. subcutaneous Enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost. 2007;5(11):2178-85.

Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, et al. Dabigatran etexilate versus Enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomized, double-blind, non-inferiority trial. Lancet. 2007;370(9591):949–56.

Eriksson BI, Dahl OE, Huo MH, Kurth AA, Hantel S, Hermansson K, et al. Oral Dabigatran versus Enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*), a double-blind, non-inferiority trial. Thromb Haemost. 2011;105:721–9.

Malhotra R, Babhulkar S, Sanjib KB, Clemens A, Dadi A, Iyer R, Kamath S et al. Thromboprophylaxis with Dabigatran after total hip arthroplasty in Indian patients: A subanalysis of a double-blind, double dummy, randomized RE-NOVATE II study. Asian J Surg. 2017;40:145-51.

Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, et al. Treatment of Acute Venous Thromboembolism with Dabigatran or Warfarin and Pooled Analysis. Circulation. 2014;129:764-72.

Cohen AT, Hamilton M, Mitchell SA, Phatak H, Liu X, Bird A, et al. Comparison of the Novel Oral Anticoagulants Apixaban, Dabigatran, Edoxaban, and Rivaroxaban in the Initial and Long-Term Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis. PLoS One. 2015;10(12):e0144856.

Outes AG, Terleira-Fernandez AI, Suarez-Gia ML, Vargas-Castrillon E. Dabigatran, rivaroxaban, or apixaban versus Enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons. BMJ. 2012;344:e3675.

Sardar P, Chatterjee S, Chaudhari S, Lip GY. New Oral Anticoagulants in Elderly Adults: Evidence from a Meta-Analysis of Randomized Trials. Am Geriatr Soc. 2014.

Pollack CV Jr, Reilly PA, Ryn JV, Eikelboom JW, Glund S, Bernstein RA, et al. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. N Engl J Med. 2017;377:431-41.






Review Articles