Abstract
Background: Previous studies performed in 1999 and 2000 showed frequent misuse of low-molecular weight heparins (LMWHs) in France, leading to an increasing risk of bleeding. In 2002, the French Medicine Agency (Agence Française de Sécurité Sanitaire des Produits de Santé) released guidelines on the prescription and monitoring of LMWH. This study assesses LMWH use before and after the implementation of these guidelines.
Methods: We performed a ‘pre and post’ survey comparing data collected in 1999 (before guidelines) and in 2003 (1 year after guidelines) at a French university hospital. The same design and the same medical wards were used for both data-collection periods, and the data collected included patient characteristics, LWMH prescription information (daily dose, indication) and adverse drug reactions (ADRs). The main outcome was the frequency of prescription of LMWHs for curative treatment in patients with severe renal insufficiency, defined as having a creatinine clearance of ≤30 mL/min, estimated using the Cockroft formula.
Results: The analysis was performed in 332 patients in 1999 and 566 in 2003. Despite a similar frequency of prescription of LMWHs as curative treatments, the frequency with which patients with severe renal insufficiency were exposed to a LMWH as a curative treatment decreased significantly from 3.0% in 1999 to 1.0% in 2003 (p = 0.03). Compared with patients treated in 1999, those treated in 2003 were younger, more likely to be men, with a higher bodyweight and a shorter duration of hospitalisation. The incidence of haemorrhagic ADRs significantly decreased, with an odds ratio of 0.26 (95% CI 0.09, 0.73) according to the results of a multiple logistic regression analysis.
Conclusions: Our results show a better agreement of prescribing practice with contraindications and cautions about LMWH prescription in patients at risk following the introduction of guidelines on LWMHs. However, these data only reflect LMWH utilisation in a French university hospital. In order to assess the impact of the guidelines more widely, other studies should be performed, including studies in ambulatory care settings.
References
Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 188–203S
Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 401–28S
Stratton MA, Anderson FA, Bussey HI, et al. Prevention of venous thomboembolism. Adherence to the 1995 American College of Chest Physicians consensus guidelines for surgical patients. Arch Intern Med 2000; 160: 334–40
Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 338–400
Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med 1999; 341: 793–800
Ambrosi P, Calise G, Villani P, et al. Questionnaire on venous thromboembolism prevention by low molecular weight heparin in medical environment. Presse Med 2000; 29: 1447–50
Geerts WH. Strength of evidence for low-molecular-weight heparin. Chest 2002; 6: 2078–9
Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996; 334: 677–81
Cestac P, Bagheri H, Lapeyre-Mestre M, et al. Utilisation and safety of Low Molecular Weight Heparins: prospective observational study in medical inpatients. Drug Saf 2003; 26: 197–207
Gouin-Thibault I, Pautas E, Siguret V. Safety profile of different low-molecular weight heparins used at therapeutic dose. Drug Saf 2005; 28: 333–49
Agence Française de Sécurité Sanitaire des Produits de Santé. Centre Midi-Pyrénées de Pharmacovigilance — Toulouse, 1999/2001. Enquête nationale de Pharmacovigilance sur les HBPM Centre Midi-Pyrénées de Pharmacovigilance — Toulouse Les données de 2 enquetes nationales de pharmacovigilance, réalisées en 1999 et 2001 [online]. Available from URL: http://agmed.sante.gouv.fr/htm/10/hpbm/hbpmtoul.pdf [Accessed 2007 Mar 27]
French Health Products Safety Agency. Information to prescribers about low-molecular-weight heparin [online]. Available from URL: http://www.agmed.sante.gouv.fr [Accessed 2006 Dec 20]
Maguire P, Selby P. Assessing the quality of life in cancer patients. Br J Cancer 1989; 60: 437–40
Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494–50
Gerlach AT, Pickworth KK, Seth SK, et al. Enoxaparin and bleeding complications in patients with and without renal insufficiency. Pharmacotherapy 2000; 20: 771–5
Spyropoulos AC, Hurley JS, Ciesla GN, et al. Management of acute proximal deep vein thrombosis: pharmacoeconomic evaluation of outpatient treatment with enoxaparin vs inpatient treatment with unfractionated heparin. Chest 2002; 122: 108–14
Belmin J, Medjahed S, Trivalle C, et al. Heparin use in geriatrics and risk profiles of treated patients: a surbey in France. Groupe de Recherche sur l’Héparine en Gériatrie (GREHG). Presse Med 2001; 30: 101–6
Boneu B. Low molecular weight heparins: are they superior to unfractionated heparins to prevent and to treat deep vein thrombosis? Thromb Res 2000; 100(2): V113–20
Fagot JP, Flahault A, Fodil M, et al. Prophylactic prescription of low-molecular-weight heparin in the non-surgical setting: impact of recommendations. Presse Med 2001; 30: 203–8
Thorevska N, Amoateng-Adjepong Y, Sabahi R, et al. Anticoagulation in hospitalized patients with renal insufficiency: a comparison of bleeding rates with unfractionated heparin vs enoxaparin. Chest 2004; 125: 856–63
SYNERGY Trial Investigators. Enoxaparin vs unfractionated heparin in high-risk patients with non—ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA 2004; 292: 45–54
Acknowledgements
The authors have no conflicts of interest that are directly relevant to the content of this study.
The authors want to acknowledge P Cestac, P Sie, A Foulali, E Maupas, P Leger, B Fontan and P Massip for their participation and help for the first study in 1999 (published in 2002).
The manuscript was presented at the 8th annual meeting of the French Society of Pharmacology in Strasbourg, France, on 26–28 April 2004 (abstract in Fund Clin Pharmacol 2004; 18: 56) and at the 20th Conference on Pharmacoepidemiology and Therapeutic Risk Management, Bordeaux, 22–25 August 2004 (abstract in Pharmacoepidemiol Drug Saf 2004; 13: S149).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Leclerc-Foucras, S., Bagheri, H., Samii, K. et al. Modifications of Low-Molecular Weight Heparin Use in a French University Hospital after Implementation of New Guidelines. Drug-Safety 30, 409–417 (2007). https://doi.org/10.2165/00002018-200730050-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002018-200730050-00004