Even with optimal anticoagulant therapy, as many as 8 percent of cancer patients experience recurrent venous thromboembolism (VTE) within six months of their index event.1 Unfortunately, there is no high-quality evidence to guide the management of anticoagulation failure in such patients. Using an observational study design, Dr. Sam Schulman and colleagues provide us with more information about how cancer patients are treated after a breakthrough VTE, and how frequently various anticoagulation strategies are associated with outcomes such as (second) recurrent VTE and major bleeding.
The authors included data on 212 patients who both had cancer and experienced VTE despite anticoagulant therapy. Data from approximately one-third of the patients were gathered retrospectively; the other two-thirds of included patients were studied in a prospective fashion. During the three months after their breakthrough event, the treatment used for each patient was recorded, and all patients were followed for VTE events, major bleeding, residual thrombosis symptoms, and death. Event rates associated with the different treatment strategies were compared using Cox proportional hazards regression. Within this cohort of patients who had failed some sort of anticoagulant, 59 percent had adenocarcinoma and 73 percent had known metastases. When they experienced their breakthrough event, 70 percent of patients were using low-molecular-weight heparin (LMWH), while 27 percent were on a vitamin K antagonist (VKA). While insufficiently aggressive anticoagulation probably explained at least some of the treatment failures, 70 percent of included patients were known to be receiving a therapeutic or supratherapeutic dose at the time they experienced a qualifying event. The treatment used by the local physician after the index event was unchanged anticoagulant (and unchanged, therapeutic dose) in 33 percent, unchanged anticoagulant (but dose increased) in 31 percent, and a different anticoagulant in 24 percent (most of these patients switched from VKA to LMWH). During the subsequent three months, 8 percent had major bleeding, 11 percent had another VTE, and 27 percent died. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.11-0.70) but was similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63).
In Brief
Although the observational nature of this study is limited by the authors’ inability to adjust for potential confounding variables, Dr. Schulman and colleagues have provided important, new information that may help both clinicians and investigators charged with defining the management of cancer patients who experience VTE recurrence despite anticoagulation. First, anticoagulation failure in cancer patients is associated with a guarded prognosis: more than one quarter of the persons included in this registry died within three months of their breakthrough event. Second, the present findings support the widespread practice of switching to LMWH when a cancer (or other) patient has recurrent thrombosis while taking VKA. Unfortunately, clinicians are still left without definitive evidence about how best to treat the cancer patient who experiences new VTE while on LMWH. Many physicians recommend increasing the LMWH dose (by 20%-30%) in this situation, and, the possibility of selection bias notwithstanding, the findings of Dr. Schulman and colleagues suggest that increasing the dose of LMWH is not prohibitively risky. On the other hand, the observational nature and small size of this registry leave us uncertain about whether (or to what extent) this dose escalation strategy is beneficial.
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Competing Interests
Dr. Garcia indicated no relevant conflicts of interest.
