Skip to main content

Advertisement

Log in

Benefits versus risks of pharmacological prophylaxis to prevent symptomatic venous thromboembolism in unselected medical patients revisited. Meta-analysis of the medical literature

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

Abstract

A significant proportion of the outcomes reported in trials assessing venous thromboembolism (VTE) prophylaxis in medical patients are related to asymptomatic events found on routine imaging studies. The implications of these events are controversial. Moreover, such trials did not always reflect the patient mix in today’s internal medicine departments. We summarized the evidence assessing the rate of symptomatic VTE events and the benefit of pharmacological prophylaxis in unselected medical patients, and formally evaluated the benefit versus risk of this intervention. We searched MEDLINE, EMBASE and CENTRAL until June 2011 for studies that prospectively followed cohorts of medical patients and assessed the rates of VTE, and randomized controlled trials reporting the effect of prophylaxis on these events, at 3 weeks and 3 months. Eight trials were included. The rates of symptomatic VTE were 0.69 and 3.7 % for short term and long term follow-up periods, respectively. In the interventional meta-analysis, the odds ratio (OR) for overall mortality and for symptomatic VTE at 3 weeks were 0.93 and 0.59, favouring intervention. The OR for major bleeding at 3 weeks was 2.0, favouring no intervention. None of these results were statistically significant. The number needed to treat to prevent one overt VTE event was 292, while the number needed to treat for an additional major bleeding was 336. In unselected medical patients, the rate of symptomatic VTE is lower than the reported overall VTE rate, and the benefit to risk ratio of pharmacological intervention for alleviating this condition in at-risk medical inpatient is questionable. Further specifying the population at risk for an overt VTE, and the clinical significance of asymptomatic events, is warranted.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Antiplatelet Trialists’ Collaboration (1994): Collaborative overview of randomised trials of antiplatelet therapy. III. Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. BMJ.;308:235–246

    Google Scholar 

  2. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM, Melton LJI (2000) Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 160:809–815

    Article  PubMed  CAS  Google Scholar 

  3. Anderson FAJ, Wheeler HB, Goldberg RJ (1991) A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT Study. Arch Intern Med 151:933–938

    Article  PubMed  Google Scholar 

  4. Goldhaber SZ, Dunn K, MacDougall RC (2000) New onset of venous thromboembolism among hospitalized patients at Brigham and women’s hospital is caused more often by prophylaxis failure than by withholding treatment. Chest 118:1680–1684

    Article  PubMed  CAS  Google Scholar 

  5. Goldhaber SZ, Tapson VF (2004) A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 93:259–2562

    Article  PubMed  Google Scholar 

  6. Wein L, Wein S, Haas SJ, Shaw J, Krum H (2007) Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients. Arch Intern Med 14:1476–1486

    Article  Google Scholar 

  7. Kanaan AO, Silva MA, Donovan JL, Roy T, Al-Homsi AS (2007) Meta-analysis of venous thromboembolism prophylaxis in medically ill patients. Clin Ther 29(11):2395–2405

    Article  PubMed  CAS  Google Scholar 

  8. 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

    PubMed  Google Scholar 

  9. Geerts WH, Bergqvist D, Pineo GF et al (2008) Prevention of venous thromboembolism: American college of chest physicians evidence-based clinical practice guidelines (8th edn). Chest 133(Suppl 6):381S–453S

    Article  PubMed  CAS  Google Scholar 

  10. Duckit R, Palsson R, Bosanka L, Dagna L, Durusu Tanriover M, Vardi M et al (2010) Common diagnoses in internal medicine in Europe 2009: a pan-European, multi-centre survey. Eur J Intern Med 21(5):449–452

    Article  Google Scholar 

  11. Cohen AT, Tapson VF, Bergmann JF, Goldhaber SZ, Kakkar AK, Deslandes B et al (2008) Venous thromboembolism risk and prophylaxis in the acute care setting (ENDORSE study): a multinational cross-sectional study. Lancet 371(9610):387–394

    Article  PubMed  Google Scholar 

  12. Anderson FA, Goldhaber SZ, Tapson VF, Bergmann JF, Kakkar AK, Deslandes B et al (2010) Improving practices in US hospitals to prevent venous thromboembolism: lessons from ENDORSE. Am J Med 123(12):1099–1106

    Article  PubMed  Google Scholar 

  13. Kucher N, Koo S, Quiroz R, Cooper JM, Paterno MD, Soukonnikov B et al (2005) Electronic alerts to prevent venous thromboembolism among hospitalized patients. N Engl J Med 352:969–977

    Article  PubMed  CAS  Google Scholar 

  14. Lederle FA, Sacks JM, Fiore L, Landefeld CS, Steinberg N, Peters RW et al (2006) The prophylaxis of medical patients for thromboembolism pilot study. Am J Med 119(1):54–59

    Article  PubMed  Google Scholar 

  15. Metlay JP, Fine MJ, Schulz R, Marrie TJ, Coley CM, Kapoor WN et al (1997) Measuring symptomatic and functional recovery in patients with community-acquired pneumonia. J Gen Intern Med 12(7):423–430

    Article  PubMed  CAS  Google Scholar 

  16. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12

    Article  PubMed  CAS  Google Scholar 

  17. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP et al (2007) The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453–1457

    Article  Google Scholar 

  18. Cohen AT, Davidson BL, Gallus AS, Lassen MR, Prins MH, Tomkowski W et al (2006) Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 332(7537):325–329

    Article  PubMed  CAS  Google Scholar 

  19. Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C et al (1999) A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med 341(11):793–800

    Article  PubMed  CAS  Google Scholar 

  20. Leizorovicz A, Cohen AT, Turpie AGG, Olsson CG, Vaitkus PT, Goldhaber SZ (2004) Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 110(7):874–879

    Article  PubMed  CAS  Google Scholar 

  21. Dahan R, Houlbert D, Caulin C, Cuzin E, Viltart C, Woler M et al (1986) Prevention of deep vein thrombosis in elderly medical in-patients by a low molecular weight heparin: a randomized double-blind trial. Haemostasis 16(2):159–164

    PubMed  CAS  Google Scholar 

  22. Bergmann JF, Neuhart E (1996) A multicenter randomized double-blind study of enoxaparin compared with unfractionated heparin in the prevention of venous thromboembolic disease in elderly in-patients bedridden for an acute medical illness. The Enoxaparin in Medicine Study Group. Thromb Haemost 76(4):529–534

    PubMed  CAS  Google Scholar 

  23. Gussoni G, Campanini M, Silingardi M, Scannapieco G, Mazzone A, Magni G et al (2009) In-hospital symptomatic venous thromboembolism and antithrombotic prophylaxis in internal medicine. Findings from a multicenter, prospective study. Thromb Haemost 101(5):893–901

    PubMed  CAS  Google Scholar 

  24. Oger E, Bressollette L, Nonent M, Lacut K, Guias B, Couturaud F et al (2002) High prevalence of asymptomatic deep vein thrombosis on admission in a medical unit among elderly patients. Thromb Haemost 88(4):592–597

    PubMed  CAS  Google Scholar 

  25. Lederle FA, Zylla D, MacDonald R, Wilt TJ (2011) Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American college of physicians clinical practice guideline. Ann Intern Med 155:602–615

    PubMed  Google Scholar 

  26. Qaseem A, Chou R, Humphrey LL, Starkey M, Shekelle P (2011) Physicians. ftCGCotACo. Venous thromboembolism prophylaxis in hospitalized patients: a clinical practice guideline from the American college of physicians. Ann Intern Med 155:625–632

    PubMed  Google Scholar 

  27. Vaitkus PT, Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Goldhaber SZ et al (2005) Mortality rates and risk factors for asymptomatic deep vein thrombosis in medical patients. Thromb Haemost 93:76–79

    PubMed  CAS  Google Scholar 

  28. Engelke C, Rummeny EJ, Marten K (2006) Pulmonary embolism at multi–detector row CT of chest: one year survival of treated and untreated patients. Radiology 239(2):246–255

    Article  Google Scholar 

  29. den Exter PL, Hooijer J, Dekkers OM, Huisman MV (2011) Risk of recurrent venous thromboembolism and mortality in patients with cancer incidentally diagnosed with pulmonary embolism: a comparison with symptomatic patients. J Clin Oncol 29(17):2405–2409

    Article  Google Scholar 

  30. Cohen AT, Tapson VF, Bergmann JF, Goldhaber SZ, Kakkar AK, Deslandes B et al (2008) Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 371(9610):387–394

    Article  PubMed  Google Scholar 

  31. Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M et al (2010) A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua prediction score. J Thromb Haemost 8:2450–2457

    Article  PubMed  CAS  Google Scholar 

  32. National Institute for Health and Clinical Excellence—venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. Methods, evidence, and guidance: National Clinical Guideline Centre—acute and chronic conditions2010

  33. Alikhan R, Cohen AT, Combe S, Samama MM, Desjardins L, Eldor A et al (2003) Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study. Blood Coagul Fibrinolysis 14(4):341–346

    Article  PubMed  CAS  Google Scholar 

  34. Andrade Ede O, Binda FA, Silva AM, Costa TD, Fernandes MC, Fernandes MC (2009) Risk factors and prophylaxis for venous thromboembolism in hospitals in the city of Manaus, Brazil. J Bras Pneumol 35(2):114–121

    Article  PubMed  Google Scholar 

  35. Weill-Engerer S, Meaume S, Lahlou A, Piette F, Saint-Jean O, Sachet A et al (2004) Risk factors for deep vein thrombosis in inpatients aged 65 and older: a case-control multicenter study. J Am Geriatr Soc 52(8):1299–1304

    Article  PubMed  Google Scholar 

  36. Buller HR, Cohen AT, Davidson B, Decousus H, Gallus AS, Gent M et al (2007) Extended prophylaxis of venous thromboembolism with idraparinux. N Engl J Med 357(11):1105–1112

    Article  PubMed  CAS  Google Scholar 

  37. Li XY, Fan J, Cheng YQ, Wang Y, Yao C, Zhong NS (2011) Incidence and prevention of venous thromboembolism in acutely ill hospitalized elderly Chinese. Chin Med J 124(3):335–340

    PubMed  Google Scholar 

  38. Mahe I, Bergmann JF, D’Azemar P, Vaissie JJ, Caulin C (2005) 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(5–6):347–351

    Article  PubMed  CAS  Google Scholar 

  39. Bergmann JF, Neuhart E (1996) A multicenter randomized double-blind study of enoxaparin compared with unfractionated heparin in the prevention of venous thromboembolic disease in elderly in-patients bedridden for an acute medical illness. Thromb Haemost 76(4):529–534

    PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare no conflict of interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Moshe Vardi.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 85 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vardi, M., Steinberg, M., Haran, M. et al. Benefits versus risks of pharmacological prophylaxis to prevent symptomatic venous thromboembolism in unselected medical patients revisited. Meta-analysis of the medical literature. J Thromb Thrombolysis 34, 11–19 (2012). https://doi.org/10.1007/s11239-012-0730-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-012-0730-x

Keywords

Navigation