Cancer Patients at High Recurrence Risk for Venous Thromboembolism Should Be Considered for Secondary Prophylaxis

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The risk of recurrence of venous thromboembolism in cancer patients can be stratified. “In particular, patients with brain, lung, stage IV pancreatic or ovarian cancer, myeloproliferative or myelodysplastic disorders, [other] stage IV cancer, cancer stage progression or leg paresis have the highest risk for recurrence and should be considered for secondary prophylaxis.” Cheng E. Chee, MD, of Case Western Reserve University School of Medicine, Cleveland, and colleagues reached these conclusions after conducting a population-based cohort study of active cancer patients with incident venous thromboembolism.

Published in Blood, the study analyzed data for residents of Olmsted County, Minnesota, residents with active cancer-related incident venous thromboembolism over the 35-year period from 1966 to 2000, who survived at least 1 day. “We estimated [venous thromboembolism] recurrence, bleeding on anticoagulant therapy, and survival, and tested cancer and non-cancer characteristics and secondary prophylaxis as predictors of [venous thromboembolism] recurrence and bleeding, using Cox proportional hazards modeling,” the researchers explained.

“Of 477 patients, 139 developed recurrent [venous thromboembolism] over 1,533 person-years of follow-up. The adjusted 10-year cumulative [venous thromboembolism] recurrence rate was 28.6%. The adjusted 90-day cumulative incidence of major bleeding on anticoagulation was 1.9%. Survival was significantly worse for cancer patients with recurrent [venous thromboembolism] (particularly pulmonary embolism) and with bleeding on anticoagulation,” they reported.

“In a multivariable model, brain, lung and ovarian cancer, myeloproliferative or myelodysplastic disorders, stage IV pancreatic cancer, other stage IV cancer, cancer stage progression and leg paresis were associated with an increased hazard, and warfarin therapy with a reduced hazard, of recurrent [venous thromboembolism]. Recurrence rates were significantly higher for cancer patients with ≥ 1 vs no predictors of recurrence, suggesting that these predictors may be useful for stratifying recurrence risk.” Not found to be independent predictors of venous thromboembolism recurrence were cancer grade and histology, chemotherapy and the type administered, central venous catheter, radiation therapy, and venous invasion.

The authors noted that the since the seminal study demonstrating the superiority of low–molecular-weight heparin in preventing venous thromboembolism recurrence among active cancer patients was published in 2003 and patients in their study were followed until 2000, “essentially none of our [venous thromboembolism] cases received acute treatment or secondary prophylaxis with [low–molecular-weight heparin]. While [low–molecular-weight heparin] secondary prophylaxis is recommended over warfarin, many patients are unable to afford or tolerate parenteral [low–molecular-weight heparin]. Our findings show that warfarin secondary prophylaxis is an effective (albeit, secondary) alternative to [low–molecular-weight heparin].” In the study, secondary prophylaxis with warfarin decreased venous thromboembolism by about 60%.

“There is always a tension between preventing [venous thromboembolism] recurrence and causing bleeding with anticoagulation therapy,” the researchers noted. “We estimated that, in the absence of anticoagulation therapy, 35 additional deaths from recurrent [venous thromboembolism] and six fewer deaths from bleeding would have occurred. Given that [low–molecular-weight heparin] is more efficacious than warfarin with no significant difference in bleeding, the number of deaths averted by [low–molecular-weight heparin] therapy might be greater.” ■

Chee CE, et al: Blood. April 29, 2014 (early release online).




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