Review

Areas of Uncertainty in Prophylaxis of Venous Thromboembolism in Unselected Subjects

Authors: Marco Cei, MD, Nicola Mumoli, MD

Abstract

In the last decade, parenteral anticoagulants have proven to be effective in the prevention of venous thromboembolism (VTE) in patients admitted to hospitals. Despite this, some registry studies have shown that pharmacological prophylaxis is still widely underused. We performed a literature search to identify important knowledge gaps in the use of VTE prophylaxis that were not addressed by previous published reports. MEDLINE and HighWire databases covering the years 1999-2009 were searched; only clinical trials of unselected adult subjects were included. Two reviewers independently selected studies and extracted data on inclusion and exclusion criteria, age, weight, comorbidities, study designs, and endpoints. Five of 113 relevant studies were identified from the literature search. Knowledge gaps were disclosed in subject inclusion, exclusion, and stratification regarding young age, under- and overweight, comorbidities, and the selection of clinically significant endpoints. Uncertainties in the dosage, risk stratification of subjects, and effect on hard endpoints as prevention of pulmonary embolism or reduction of mortality reduce the impact of VTE prevention clinical trials.

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References

1. Francis CW. Prophylaxis for thromboembolism in hospitalized medical patients. N Engl Med 2007;356:1438-1445.
 
2. Halkin H, Goldberg J, Modan M, et al. Reduction of mortality in general medical in-patients by low-dose heparin prophylaxis. Ann Intern Med 1982;96:561-565.
 
3. 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.
 
4. Leizorovicz A, Cohen AT, Turpie AGG, et al. Randomized, placebo-controlled trials of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004;110:874-879.
 
5. Cohen AT, Davidson BL, Gallus AS, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ2006;332:325-329.
 
6. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:338S-400S.
 
7. King CS, Holley AB, Jackson JL, et al. Twice vs three times daily heparin dosing for thromboembolism prophylaxis in the general medical population. A metaanalysis. Chest 2007;131:507-516.
 
8. Tapson VF, Decousus H, Pini M, et al. Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients. Findings from the International Medical Prevention Registry on Venous Thromboembolism. Chest 2007;132;936-945.
 
9. Cohen AT, Tapson VF, Bergmann JF, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 2008;371:387-394.
 
10. Lederle FA, Sacks JM, Fiore L, et al. The prophylaxis of medical patients for thromboembolic pilot study. Am J Med 2006;119:54-59.
 
11. Altman DG. Confidence intervals for the number needed to treat. BMJ 1998;317:1309-1312.
 
12. PREPIC Study Group. Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study. Circulation 2005;112:416-422.
 
13. Dhôte R, Pellicer-Coeuret M, Belouet-Moreau C, et al. Venous thromboembolism in medical inpatients: prophylaxis with low-weight heparin in a university hospital and prevalence of thromboembolic events. Clin Appl Thromb Hemost 2001;7:16-20.
 
14. Kucher N, Spirk D, Baumgartner I, et al. Lack of prophylaxis before the onset of acute venous thromboembolism among hospitalized cancer patients: the SWiss Venous ThromboEmbolism Registry (SWIVTER). Ann Oncol 2009;0:mdp406v1-mdp406.
 
15. Mahé I, Bergmann JF, d'Azémar P, et al. 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 2005;61:347-351.
 
16. Kleber FX, Witt C, Vogel GV, et al. Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease. Am Heart J 2003;145:614-621.
 
17. Rocha AT, Paiva EF, Lichtenstien A, et al. Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients. Vasc Health Risk Manag 2007;3:533-553.
 
18. Samama MM, Dahl OE, Quinlan DJ, et al. Quantification of risk factors for venous thromboembolism: a preliminary study for the development of a risk assessment tool. Haematologica 2003;88:1410-1421.
 
19. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998;158:585-593.
 
20. Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008;133:141S-159S.
 
21. Kucher N, Leizorovicz A, Vaitkus PT, et al. For the PREVENT Medical Thromboprophylaxis Study Group. Efficacy and safety of fixed low-dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial. Arch Intern Med 2005;165:341-345.
 
22. Nagge J, Crowther M, Hirsh J. Is impaired renal function a contraindication to the use of low-molecular-weight heparin? Arch Intern Med 2002;162:2605-2609.
 
23. Lim W, Dentali F, Eikelboom JW, et al. Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med 2006;144:673-684.
 
24. Tincani E, Mannucci C, Casolari B, et al. Safety of dalteparin for the prophylaxis of venous thromboembolism in elderly medical patients with renal insufficiency: a pilot study. Haematologica2006;91:976-979.
 
25. Douketis J, Cook D, Meade MM, et al. Prophylaxis against deep vein thrombosis in critically ill patients with severe renal insufficiency with the low-molecular-weight heparin dalteparin. An assessment of safety and pharmacodynamics: the Direct Study. Arch Intern Med 2008;168;1805-1812.
 
26. Turpie AG, Lensing AW, Fuji T, et al. Pharmacokinetic and clinical data supporting the use of fondaparinux 1.5 mg once daily in the prevention of venous thromboembolism in renally impaired patients. Blood Coagul Fibrinolysis 2009;20:114-121.
 
27. Wein L, Wein S, Haas SJ, et al. Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients. A meta-analysis of randomized controlled trials. Arch Intern Med 2007;167:1476-1486.
 
28. Hommel M, for the FISS-bis Investigators Group. Fraxiparine in Ischaemic Stroke Study (FISS-bis) [abstract]. Cerebrovasc Dis 1998;8:19.
 
29. Dentali F, Douketis JD, Gianni M, et al. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007;146:278-288.