# 236 Pharmacologic Treatment of Acute Venous Thromboembolism in Patients with Advanced Cancer

FAST FACTS AND CONCEPTS #236 PDF

AUTHORS: René Claxton MD and Robert Arnold MD

Background Venous thromboembolism (VTE) is a common complication of malignancy which carries a poor prognosis (1). This Fast Fact discusses the approach to VTE in patients with advanced cancer.

Does anticoagulation for VTE improve outcomes? There are no randomized, placebo controlled trials of anticoagulation for the treatment of VTE (2). The only study comparing heparin and warfarin for acute pulmonary embolism (PE) versus no treatment found a decrease in mortality with a number needed to treat (NNT) of four (3). Data from non-placebo controlled trials shows anticoagulation for acute VTE decreases recurrence(4) and clot propagation (5). Based on this evidence and clinical consensus, anticoagulation is recommended to decrease mortality and VTE recurrence in patients with a new VTE.

What is the best treatment for VTE for cancer patients? Current evidence-based guidelines recommend LMWH instead of oral vitamin K antagonists (e.g. warfarin) to decrease the risk of recurrent VTE in cancer patients. The CLOT trial(6) demonstrated a decreased risk for recurrent VTE in patients maintained on LMWH versus oral anticoagulation with a number needed to treat (NNT) of 13. The major risk of anticoagulation is bleeding. In the CLOT trial major bleeding* occurred in ~5% of patients regardless of the type of anticoagulation. A Cochrane reviewon the topic of anti-coagulation with LMWH versus oral anticoagulants for VTE in patients with cancer identified eight randomized controlled trials with moderate quality evidence (7). It showed a statistically significant decrease in recurrent VTE in favor of LMWH, with a relative risk of 0.51 (CI 0.35-0.74). Novel anticoagulants are under investigation, although not enough is known about them to comment on their use in advanced cancer patients.

Does the evidence supporting the use of anti-coagulation for treatment of VTE apply to cancer patients with short prognoses?Unfortunately, most studies exclude patients with increased creatinine, those in bed greater than 50% of the day, and those with less than a three-month prognosis (see Fast Fact #13). Thus, there are no research data to guide clinicians on the efficacy (does it prolong life or reduce symptoms?), safety (what is the bleeding risk?), and tolerability of treating acute VTE in cancer patients with prognoses of weeks to a few months.

What other considerations should be made in the decision to treat acute VTE in cancer patients with short prognoses?

  1. Decide whether to anticoagulate or treat symptomatically. This decision is entirely empiric and should be based on clinical judgment about prognosis, symptom burden, and patient preference. For instance, for a patient with a prior history of VTE who remains ambulatory and who develops symptomatic VTE (e.g. a painful, swollen leg), providing anti-coagulation may be appropriate to prevent additional symptomatic events. If this same patient was already bedbound with a prognosis of weeks, it is doubtful anti-coagulation would provide substantial benefit.
  2. If anticoagulation is chosen, then determine whether to use oral anticoagulants or LMWH. LWMH does not require routine laboratory testing, has few drug-drug interactions, is not diet dependent for safe administration, and is more efficacious than warfarin in trials with healthier patients. Warfarin requires frequent laboratory monitoring of the INR and has many drug-drug interactions (8). In addition, a patient’s INR is highly diet dependent and can rise dangerously in patients with diminishing oral intake, which is common for advanced cancer patients. However, LMWH is far more expensive than oral anti-coagulation. Warfarin costs approximately $0.11/day compared to $100/day for enoxaparin. This comparison does not take into account the cost of laboratory tests to monitor a patient’s INR or the administration costs for patients unable to self-administer LMWH. Given its high cost LMWH may not be available for many patients receiving hospice care.

Bottom Line The patient’s prognosis and preferences should be considered prior to starting anticoagulation therapy. Clinicians should work with hospice agencies to determine an affordable plan to safely administer and monitor anticoagulation for acute VTE in hospice patients. Clinicians should prepare patients who decide to continue anticoagulation for discontinuing it once expected survival is short or worsening risks such as uncontrolled INR become apparent.

*Major bleeding includes any bleeding associated with death, located at a critical site (intracranial, intraspinal, intraocular, retroperitoneal or pericardial area), resulting in the need for a transfusion of at least two units of blood or leading to a drop in hemoglobin of at least 2.0 g per deciliter.

References

  1. Sorensen HT, Mellemkjoer L, Olsen JH and Baron JA. Prognosis of cancers associated with venous thromboembolism.N Eng J Med.2000; 343(25):1846-1850.
  2. McManus RJ, Fitzmaurice D, Murray ET and Taylor C. Thromboembolism.Clinical Evidence. 2009; 3(208). Retrieved Oct 8, 2009 from http://clinicalevidence.bmj.com/ceweb/conditions/cvd/0208/0208.jsp
  3. Barritt DW and Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet. 1960; 1:1309-1312.
  4. Brandjes DP, Heijboer H, Büller HR, de Rijk M, Jagt H, ten Cate JW. Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal vein thrombosis.N Engl J Med. 1992; 327(21):1485-1489.
  5. Belcaro G, Laurora G, Cesarone MR et al. Prevention of the extension of distal deep venous thrombosis: A randomized controlled trial with a 6 month follow up.Minerva Med. 1997; 88(12):507-514.
  6. Lee AY, Levine MN, Baker RI et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.N Engl J Med. 2003; 349(2): 146-153.
  7. Akl EA, Barba M, Rohilla S et al. Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer.Cochrane Database Syst Rev. 2008; 16(2):CD006650.
  8. Noble SI, Shelley MD, Coles B, Willams SM, Wilcock AW, Johnson MJ. Management of venous thromboembolism in patients with advanced cancer: A systematic review and meta-analysis.Lancet Oncol. 2008; 9(6):577-584.
  9. Wright AA, Zhang B, Ray A et al. Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA. 2008;300(14):1665-1673.
  10. Miller SC, Mor V, Wu N, Gozalo P, Lapane K. Does receipt of hospice care in nursing homes improve the management of pain at the end of life? J Am Geriatr Soc. 2002; 50(3):507–515.

Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA.

Fast Facts and Concepts are edited by Drew A. Rosielle MD, Palliative Care Program, University of Minnesota Medical Center – Fairview Health Services, and are published by the End of Life/Palliative Education Resource Center at the Medical College of Wisconsin. For more information write to: drosiel1@fairview.org. More information, as well as the complete set of Fast Facts, are available at EPERC: http://www.mcw.edu/eperc. Readers can comment on this publication at the Fast Facts and Concepts Discussion Blog (http://epercfastfacts.blogspot.com).

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Claxton R, Arnold R. Pharmacologic Treatment of Acute Venous Thromboembolism in Patiens with Advanced Cancer.Fast Facts and Concepts. December 2010; 236. Available at: http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_236.htm.

Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

ACGME Competencies: Medical Knowledge, Patient Care, Systems Based Practice

Keywords: Non-pain Symptoms, Cancer