Download PDF
Thromb Haemost 2015; 114(02): 237-244
DOI: 10.1160/TH15-01-0073
Review Article
Schattauer GmbH

Post-operative arterial thrombosis with non-vitamin K antagonist oral anticoagulants after total hip or knee arthroplasty

Alessandro Squizzato
1   Research Center on Thromboembolic Disorders and Antithrombotic Therapies, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
Federico Lussana
2   Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XIII, Bergamo, Italy
3   Medicina III, Azienda Ospedaliera San Paolo, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy
,
Marco Cattaneo
3   Medicina III, Azienda Ospedaliera San Paolo, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy
› Author Affiliations
Further Information

Publication History

Received: 26 January 2015

Accepted after major revision: 04 March 2015

Publication Date:
01 December 2017 (online)

    Permissions and Reprints

Summary

The incidence of post-operative arterial thrombosis (AT) (acute myocardial infarction [AMI] and ischaemic stroke) is increased in patients undergoing total hip replacement (THR) or total knee replacement (TKR). We compared the incidence of post-operative AT in non-vitamin K antagonist oral anticoagulants (NOACs)-treated and enoxaparintreated patients, performing a systematic review of phase III randomised controlled trials (RCTs) of venous thromboembolism (VTE) prophylaxis in THR and TKR. Studies were identified by electronic search of MEDLINE and EMBASE database until July 2014. Differences between NOACs and enoxaparin groups in the efficacy and safety outcomes were expressed as odds ratios (ORs) with pertinent 95 % confidence intervals (95 % CI). Statistical heterogeneity was assessed with the I2 statistic. Eleven phase III RCTs for a total of 31,319 patients were included. Patients underwent TKR in six studies and THR in five studies. The NOACs under study were dabigatran (four studies), apixaban (three studies) and rivaroxaban (four studies). AT occurred in 0.23 % of patients on NOACs and in 0.27 % of patients on enoxaparin: the OR at fixed-effect model was 0.86 (95 % CI 0.53–1.40; I2 11 %). No differences in AT incidence among the three NOACs were observed. The incidence of major and clinically relevant bleeding was similar in NOACs and enoxaparin groups (OR 1.03, 95 % CI 0.92–1.15; I2 38 %). In conclusion, in RCTs of pharmacological VTE prophylaxis in patients undergoing THR or TKR, there was no difference in the incidence of post-operative AT among patients treated with NOACs, compared to those treated with enoxaparin.

Note: An abstract of this paper has been accepted as oral presentation at the XXIII Congress of SISET, Italian Society of Thrombosis and Haemostasis, 6–9 November 2014, Milan (Italy).

Keywords

Oral anticoagulant - myocardial infarction - stroke - total hip arthroplasty - total knee arthroplasty
 

  • References

  • 1 Falck-Ytter Y, Francis CW, Johanson NA. 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 (Suppl. 02) e278S-325S.
    CrossrefPubMedGoogle Scholar
  • 2 Wallace AW. Risk of acute myocardial infarction in patients with total hip or knee replacement: comment on “Timing of acute myocardial infarction in patients undergoing total hip or knee replacement: a nationwide cohort study”. Arch Intern Med 2012; 172: 1235-1236.
    CrossrefPubMedGoogle Scholar
  • 3 Savonitto S, Caracciolo M, Cattaneo M. et al. Management of patients with recently implanted coronary stents on dual antiplatelet therapy who need to undergo major surgery. J Thromb Haemost 2011; 09: 2133-2142.
    CrossrefPubMedGoogle Scholar
  • 4 Lalmohamed A, Vestergaard P, Klop C. et al. Timing of acute myocardial infarction in patients undergoing total hip or knee replacement: a nationwide cohort study. Arch Intern Med 2012; 172: 1229-1235.
    CrossrefPubMedGoogle Scholar
  • 5 Lalmohamed A, Vestergaard P, Cooper C. et al. Timing of stroke in patients undergoing total hip replacement and matched controls: a nationwide cohort study. Stroke 2012; 43: 3225-3229.
    CrossrefPubMedGoogle Scholar
  • 6 Lussana F, Squizzato A, Permunian ET, Cattaneo M. A systematic review on the effect of aspirin in the prevention of post-operative arterial thrombosis in patients undergoing total hip and total knee arthroplasty. Thromb Res 2014; 134: 599-603.
    CrossrefPubMedGoogle Scholar
  • 7 Husted S, de Caterina R, Andreotti F. et al. Non-vitamin K antagonist oral anticoagulants (NOACs): No longer new or novel. Thromb Haemost 2014; 111: 781-782.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
    CrossrefPubMedGoogle Scholar
  • 9 Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009; 151: 264-269. W264.
    CrossrefPubMedGoogle Scholar
  • 10 Schulman S, Angerås U, Bergqvist D. et al. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost 2010; 08: 202-204.
    CrossrefPubMedGoogle Scholar
  • 11 Higgins JP, Altman DG, Gotzsche PC. et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Br Med J 2011; 343: d5928.
    CrossrefPubMedGoogle Scholar
  • 12 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 07: 177-188.
    CrossrefPubMedGoogle Scholar
  • 13 Higgins JP, Thompson SG, Deeks JJ. et al. Measuring inconsistency in meta-analyses. Br Med J 2003; 327: 557-560.
    CrossrefPubMedGoogle Scholar
  • 14 Zou Y, Tian S, Wang Y. et al. Administering aspirin, rivaroxaban and low-molecular-weight heparin to prevent deep venous thrombosis after total knee arthroplasty. Blood Coagul Fibrinolysis 2014; 25: 660-664.
    CrossrefPubMedGoogle Scholar
  • 15 Fuji T, Fuijita S, Ujihira T. et al. Dabigatran etexilate prevents venous thromboembolism after total knee arthroplasty in Japanese patients with a safety profile comparable to placebo. J Arthroplasty 2010; 25: 1267-1274.
    CrossrefPubMedGoogle Scholar
  • 16 Turpie AGG, Bauer KA, Davidson BL. et al. for the EXPERT study group. A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for the prevention of thromboembolic events after total knee replacement (EXPERT). Thromb Haemost 2009; 101: 68-76.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Fuji T, Fujita S, Tachibana S. et al. Edoxaban versus enoxaparin for the prevention of venous thromboembolism: Pooled analysis of venous thromboembolism and bleeding from STARS E-3 and STARS J-V. ASH Annual Meeting Abstracts 2011; 118: 208.
    PubMedGoogle Scholar
  • 18 Eriksson BI, Borris LC, Friedman RJ. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358: 2765-2775.
    CrossrefPubMedGoogle Scholar
  • 19 Kakkar AK, Brenner B, Dahl OE. et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008; 372: 31-39.
    CrossrefPubMedGoogle Scholar
  • 20 Lassen MR, Ageno W, Borris LC. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358: 2776-2786.
    CrossrefPubMedGoogle Scholar
  • 21 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.
    CrossrefPubMedGoogle Scholar
  • 22 Eriksson BI, Dahl OE, Rosencher N. et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007; 370: 949-956.
    CrossrefPubMedGoogle Scholar
  • 23 Eriksson BI, Dahl OE, Rosencher N. 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; 05: 2178-2185.
    CrossrefPubMedGoogle Scholar
  • 24 Eriksson BI, Dahl OE, Huo MH. et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost 2011; 105: 721-729.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Ginsberg JS, Davidson BL, Comp PC. et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty 2009; 24: 1-9.
    CrossrefPubMedGoogle Scholar
  • 26 Lassen MR, Raskob GE, Gallus A. et al. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 2009; 361: 594-604.
    CrossrefPubMedGoogle Scholar
  • 27 Lassen MR, Raskob GE, Gallus A. et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 2010; 375: 807-815.
    CrossrefPubMedGoogle Scholar
  • 28 Lassen MR, Gallus A, Raskob GE. et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010; 363: 2487-2498.
    CrossrefPubMedGoogle Scholar
  • 29 Devereaux PJ, Goldman L, Cook DJ. et al. Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk. CMAJ 2005; 173: 627-634.
    CrossrefPubMedGoogle Scholar
  • 30 Adam SS, McDuffie JR, Lachiewicz PF. et al. Comparative effectiveness of new oral anticoagulants and standard thromboprophylaxis in patients having total hip or knee replacement: a systematic review. Ann Intern Med 2012; 159: 275-284.
    PubMedGoogle Scholar
  • 31 Gomez-Outes A, Terleira-Fernandez AI, Suarez-Gea ML. et al. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons. Br Med J 2012; 344: e3675.
    CrossrefPubMedGoogle Scholar
  • 32 Douxfils J, Buckinx F, Mullier F. et al. Dabigatran etexilate and risk of myocardial infarction, other cardiovascular events, major bleeding, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc 2014; 03: e000515.
    CrossrefPubMedGoogle Scholar
  • 33 Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med 2012; 172: 397-402.
    CrossrefPubMedGoogle Scholar
  • 34 Mangano DT, Browner WS, Hollenberg M. et al. Association of perioperative myocardial ischaemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. The Study of Perioperative Ischaemia Research Group. N Engl J Med 1990; 323: 1781-1788.
    CrossrefPubMedGoogle Scholar