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Extended duration VTE prophylaxis in cancer patients
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Venous thromboembolism is a significant problem in the care of patients with cancer, increasing morbidity, mortality and costs of care. They are at a much higher risk of developing VTE — up to sevenfold — with an incidence of up to 20% based on clinical diagnosis and a much higher incidence based on autopsy diagnosis. Cancer patients with VTE also have a much higher death rate compared to VTE patients without cancer, as well as compared to cancer patients without VTE. Some other risk factors for VTE include advanced age, prior history of VTE, obesity, smoking, immobility, infection, chronic heart failure and pulmonary disorders, in addition to vascular access devices and chemotherapy. The etiology of VTE in cancer patients is multifactorial including endothelial damage, circulatory stasis and hypercoagulability.
Hospitalized cancer patients have a much higher risk of developing VTE than outpatient cancer patients. This risk does not dramatically diminish right after hospital discharge; it is seen for at least three to four weeks after discharge and many VTE episodes are diagnosed during this time period.
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VTE prophylaxis with anticoagulants is a standard recommendation for hospitalized cancer patients. The ASCO, National Comprehensive Cancer Network, and CHEST guidelines all concur that surgical and medically ill cancer inpatients be given anticoagulant VTE prophylaxis, unless it is contraindicated due to an elevated risk of bleeding complications. The original trials demonstrating VTE protection in cancer patients used treatment durations of about six to 14 days or until hospital discharge. Additional studies have researched the use of anticoagulants in the setting of prolonged VTE prophylaxis after hospital discharge.
Trial data
One group of researchers (Bergqvist, 2002) studied prolonged VTE prophylaxis in a group of more than 300 cancer patients undergoing curative abdominal or pelvic surgery. The median age of these patients was about 65 and most had gastrointestinal or gynecologic cancers. All of these patients received enoxaparin (Lovenox, Sanofi Aventis) 40 mg subcutaneously daily, starting preoperatively and lasting six to 10 days. The patients were then randomly assigned to either placebo or enoxaparin 40 mg subcutaneously daily for 25 to 31 more days. All patients underwent venography between days 25 and 31, or earlier if symptomatic of a VTE. The results from this trial are shown in table 1.
In this trial, extended prophylaxis with enoxaparin dramatically reduced the incidence of VTE. The benefit persisted through the three-month evaluation. The number of patients needed to treat was 14 to prevent one VTE episode. Number needed to treat values of 20 and under are generally thought to be clinically relevant. The rate of major bleeding complications was not statistically different between the two groups.
Similar results were found by another group of researchers (Rasmussen, 2006) who studied prolonged prophylaxis in a group of general patients receiving major abdominal surgery. The median age of the participants was 67; 7.3% of patients had cancer. All patients received dalteparin (Fragmin, Eisai) 5,000 units subcutaneously daily for seven days. They were then randomly assigned placebo or dalteparin 5,000 units subcutaneously daily for an additional 21 days. Assessment for VTE was conducted by venography at day 28. These trial results are shown in table 2.
In this trial, prolonged VTE prophylaxis reduced the rate of VTE by more than 50%. The number needed to treat was 12. The rate of major bleeding complications was not statistically different between the two groups. Although this trial did not specifically study cancer patients, the results are strikingly similar to the first trial cited.
Until recently, there has not been any information regarding the use of extended VTE prophylaxis in medically ill cancer patients. One group of researchers (Hull, 2006; Jaffer, 2008) has presented preliminary information on a trial in higher-risk hospitalized medically ill patients. Just as in the previous study, cancer patients formed only a subset of enrolled patients. This group enrolled patients that were older than 40, had recent immobility, predefined medical illness and total bed rest, or patients with bed rest with bathroom privileges and either age older then 75, history of VTE or cancer. All patients received enoxaparin 40 mg subcutaneously daily for six to 14 days, and then were randomly assigned placebo or enoxaparin 40 mg subcutaneously daily for 24 to 32 days. VTE was assessed by ultrasonography at day 28 or earlier if the patient was symptomatic. The results from this trial are shown in table 3.
This study showed a relative risk reduction of nearly 50%, echoing the results in the previous two studies. The number needed to treat to prevent one VTE episode was 46. This number is higher than that seen in the previous studies due to the lower underlying incidence of VTE in this patient population. The rate of major bleeding complications was slightly but significantly higher in the extended prophylaxis group.
These studies show the potential benefit of extended duration VTE prophylaxis after hospitalization for cancer patients. Preventing VTE episodes can reduce morbidity and mortality in these patients. Extended duration VTE prophylaxis for hospitalized cancer patients has not been as widely utilized as inpatient prophylaxis. Some of the barriers include the perceived risk of bleeding, the need for ongoing subcutaneous injections, and the high cost of the medications and insurance co-pays.
Lisa K. Lohr, PharmD, BCPS, BCOP, is a Clinical Pharmacist in Oncology and Bone Marrow Transplantation in the Department of Pharmacy Services at the University of Minnesota Medical Center and is a HemOnc Today Editorial Board member.
For more information:
- Bergqvist D. N Engl J Med. 2002;346:975.
- Hull RD. J Thromb Thrombolysis. 2006;22:31.
- Jaffer AK. Cleveland Clin J Med. 2008;75(S3):S7.
- Rasmussen MS. J Thromb Haemost. 2006;4:2384.