Skip to main content

Advertisement

SpringerLink
Log in

Nadroparin for the prevention of venous thromboembolism in nonsurgical patients: a systematic review and meta-analysis

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Anticoagulant thromboprophylaxis with low molecular weight heparin is widely used in nonsurgical settings. To obtain best estimates of the effects of nadroparin for the prevention of venous thromboembolism (VTE) in nonsurgical patients, we conducted a systematic review and meta-analysis. Data sources were Medline, Embase, and Cochrane Library supplemented with conference abstracts, without language restrictions. Selection criteria were randomized controlled trials with nadroparin at prophylactic dose in adult nonsurgical patients. Main efficacy outcomes were major VTE (the composite of symptomatic deep vein thrombosis, symptomatic pulmonary embolism, asymptomatic proximal deep vein thrombosis and VTE-related death) and symptomatic VTE. The main safety outcome was major bleeding. We expressed treatment effects as risk ratios. Ten studies (4 vs. placebo or no treatment, 4 vs. UFH, 1 vs. fondaparinux and 1 vs. warfarin) enrolling a total of 7658 patients were included. In comparison with placebo, nadroparin reduced major VTE by about one-half (RR 0.48, 95% CI 0.24–0.97) with a consistent effect on symptomatic VTE (RR 0.69, 95% CI 0.46–1.05) and no increase in major bleeding (RR 1.51, 95% CI 0.40–5.79). In comparison with other pharmacological prophylaxis, nadroparin was similarly efficacious for prevention of major VTE (RR 1.14, 95% CI 0.63–2.10) and symptomatic VTE (RR 1.10, 95% CI 0.51–2.35) and produced similar effects on major bleeding (RR 0.60, 95% CI 0.25–1.50). Five studies were open label, and for three of these the adjudication method was not described or not blinded. In nonsurgical populations at risk of VTE, nadroparin reduced VTE by about one half compared with placebo or no treatment and appeared similarly effective and safe as other prophylactic anticoagulants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kahn SR, Lim W, Dunn AS (2012) Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of Chest Physicians evidence-based clinical practice guidelines. Chest 141:e195S–e226S

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009(339):b2535. doi:10.1136/bmj.b2535

    Article  Google Scholar 

  3. Higgins JPT, Green S (eds) (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration. www.cochrane-handbook.org

  4. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  5. Agnelli G, Gussoni G, Bianchini C, Verso M, Mandalà M, Cavanna L, Barni S, Labianca R, Buzzi F, Scambia G, Passalacqua R, Ricci S, Gasparini G, Lorusso V, Bonizzoni E, Tonato M (2009) Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol 10:943–949

    Article  CAS  PubMed  Google Scholar 

  6. Aquino J-P, Gambier A, Ducros JJ (1990) Book: prevention of thromboembolic accidents in elderly subjects with nadroparin. In: Bounameaux H, Samama M, ten Cate JW (eds) Fraxiparine, Second International Symposium. Schattauer, New York. pp 51–4

  7. Forette B, Wolmark Y (1995) Calcium nadroparin in the prevention of thromboembolic disease in elderly subjects. Study of tolerance. Presse Med 24:567–571

    CAS  PubMed  Google Scholar 

  8. Fraisse F, Holzapfel L, Couland JM, Simonneau G, Bedock B, Feissel M, Herbecq P, Pordes R, Poussel JF, Roux L (2000) Nadroparin in the prevention of deep vein thrombosis in acute decompensated COPD. The Association of Non-University Affiliated Intensive Care Specialist Physicians of France. Am J Respir Crit Care Med 161:1109–1114

    Article  CAS  PubMed  Google Scholar 

  9. Harenberg J, Roebruck P, Heene DL (1996) Subcutaneous low-molecular-weight heparin versus standard heparin and the prevention of thromboembolism in medical inpatients. The Heparin Study in Internal Medicine Group. Haemostasis 26:127–139

    CAS  PubMed  Google Scholar 

  10. Kujath P, Spannagel U (1993) Habscheid W Incidence and prophylaxis of deep venous thrombosis in outpatients with injury of the lower limb. Haemostasis 23(Suppl 1):20–26

    PubMed  Google Scholar 

  11. Mahé I, Bergmann JF, d’Azémar P, Vaissie JJ (2005) Caulin C Lack of effect of a low-molecular-weight heparin (nadroparin) on mortality in bedridden medical in-patients: a prospective randomised double-blind study. Eur J Clin Pharmacol 61:347–351

    Article  PubMed  Google Scholar 

  12. Manciet G., Vergnes C, Vaissié JJ, et al. (1990) Book: A study on the efficacy and tolerance of Fraxiparine during long-term therapy of the elderly. In: Bounameaux H, Samama M, ten Cate JW (eds) Fraxiparine, Second International Symposium. Schattauer, New York, pp 55–62

  13. Mismetti P, Mille D, Laporte S, Charlet V, Buchmüller-Cordier A, Jacquin JP, Fournel P, Dutrey-Dupagne C (2003) Decousus H Low-molecular-weight heparin (nadroparin) and very low doses of warfarin in the prevention of upper extremity thrombosis in cancer patients with indwelling long-term central venous catheters: a pilot randomized trial. Haematologica 88:67–73

    CAS  PubMed  Google Scholar 

  14. Samama CM, Lecoules N, Kierzek G, Claessens YE, Riou B, Rosencher N, Mismetti P, Sautet A, Barrellier MT, Apartsin K, Jonas M, Caeiro JR, van der Veen AH, Roy PM (2013) Comparison of fondaparinux with low molecular weight heparin for venous thromboembolism prevention in patients requiring rigid or semi-rigid immobilization for isolated non-surgical below-knee injury. J Thromb Haemost 11:1833–1843

    Article  CAS  PubMed  Google Scholar 

  15. Dentali F, Douketis JD, Gianni M, Lim W, Crowther MA (2007) Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 146:278–288

    Article  PubMed  Google Scholar 

  16. Mismetti P, Laporte-Simitsidis S, Tardy B et al (2000) Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 83:14–19

    CAS  PubMed  Google Scholar 

  17. Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF (2011) LIFENOX investigators. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med 365(26):2463–2472

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge Steven Quentzel for editorial support.

Authors Contribution

WA, JB, and JWE reviewed the data and wrote the article. MC carried out the statistical analyses and contributed to sections on methods and study quality and identification.

Funding

Steven Quentzel received financial support from Aspen for editorial assistance.

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Insubria, Viale Borri 57, 21100, Varese, Italy

    Walter Ageno

  2. McMaster University, Hamilton Health Sciences, Hamilton, ON, Canada

    Jacqueline Bosch & John W. Eikelboom

  3. UMR CNRS 5558, Service de pharmacologie, Lyon, France

    Michel Cucherat

Authors
  1. Walter Ageno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacqueline Bosch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michel Cucherat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John W. Eikelboom
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Walter Ageno.

Ethics declarations

Conflicts of interests

Drs. Ageno, Cucherat and Eikelboom have received honoraria and research support from companies that market anticoagulants for prevention of VTE.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ageno, W., Bosch, J., Cucherat, M. et al. Nadroparin for the prevention of venous thromboembolism in nonsurgical patients: a systematic review and meta-analysis. J Thromb Thrombolysis 42, 90–98 (2016). https://doi.org/10.1007/s11239-015-1294-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-015-1294-3

Keywords

Search

Navigation