During the ICTHIC webinar “CAT management: challenges in different cancer populations”, Prof Walter Ageno gave a lecture on managing cancer-associated thrombosis (CAT) in challenging subpopulations. He focused on three topics: patients with unsuspected and suspected venous thromboembolism (VTE), patients with high bleeding risk cancer (e.g., unresected gastrointestinal tumors), and patients with cancer types with less evidence (e.g., primary brain tumors or metastases).
Here, we summarize the key messages of his speech. You can watch Walter Ageno’s speech and the Q&A period in the video below. You can also watch the full webinar recording here.
Symptomatic vs unsuspected pulmonary embolism
A recent meta-analysis analyzed the clinical outcomes in patients with incidentally detected, unsuspected VTE (pulmonary embolism and deep vein thrombosis), including randomized control trials and observational studies . For patients with unsuspected VTE, guidelines have long recommended the same therapeutic approach used for symptomatic VTE, even though evidence has always been less robust for asymptomatic patients .
Comparing the incidence of recurrent VTE at 6 months in patients with cancer, the rates of recurrent VTE are significantly lower among patients with incidental VTE than those with symptomatic events (risk ratio [RR]: 0.62, 95% CI: 0.44–0.87) . In addition, comparing the incidence of major bleeding events at 6 months, the rates of major bleeding complications from anticoagulant therapy are higher (not statistically significant) in patients with incidental VTE (RR: 1.47, 95% CI: 0.99–2.20). Based on the randomized controlled trials included in the meta-analysis, patients with unsuspected VTE seem to have a lower risk of recurrence and a higher risk of bleeding .
The results of other observational studies are consistent with this for recurrent VTE . Patients with incidental VTE had a lower risk of thrombotic events but not of major bleeding, for which the rates were higher in patients with incidentally detected VTE .
These data highlight a consistency regarding the risk of recurrent VTE, suggesting that patients with unsuspected VTE and suspected VTE are not identical in terms of risk of outcome events. Therefore, developing a more individualized approach for both intensity and duration of anticoagulation in patients with incidentally detected VTE might be relevant. Future studies are needed to identify risk factors and lower-risk cancer patients with incidental VTE for whom limited duration of anticoagulation could be considered.
Patients with cancer at high bleeding risk
A Canadian Expert Consensus Panel provided guidelines about anticoagulant treatment for the acute and extended treatment of symptomatic and incidental VTE to prevent recurrent VTE and minimize the bleeding risk in patients with cancer .
Well-documented risk factors for bleeding include gastrointestinal (GI) toxicity, active gastrointestinal or urothelial cancer, thrombocytopenia (<50,000 platelet/ml), renal impairment, previous bleeding in other sites .
In the presence of these factors, the use of low-molecular-weight heparin (LMWH) may be preferred over the use of direct oral anticoagulants (DOACs) .
Two randomized clinical trials first pointed out the relationship between the use of DOACs and a higher risk of major bleeding in patients with GI cancer.
The Hokusai-VTE Cancer study compared edoxaban with dalteparin in 1050 patients with CAT. Compared with dalteparin, edoxaban was associated with an absolute 3.4% reduction in the risk of recurrent VTE and an absolute 2.9% increase in the risk of major bleeding. Further analysis identified that the excess of major bleeding with edoxaban was confined to patients with GI cancer .
These results were confirmed by the SELECT-D trial and led to caution with the use of DOACs in patients with GI cancer .
A couple of years later, the CARAVAGGIO trial showed that the incidence of major bleeding was similar between patients with GI cancer and patients with other types of cancers. The results of the CARAVAGGIO study support the administration of apixaban to a larger population of cancer patients than previously recommended by guidelines, including patients with GI cancer .
However, the study also showed that, among patients with GI cancer, all the bleeding events occurred in patients with non-resected GI cancer, pointing out a particular caution for this subpopulation when using DOACs .
Cancer with cancer types with less evidence
Some cancer types are less represented or not represented in the randomized clinical trials, and one example is brain tumors.
Background VTE commonly occurs in patients with brain tumors. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines suggest using either LMWH or DOACs to treat established VTE in cancer patients with brain tumors .
Because of the high rate of spontaneous intracranial hemorrhage (ICH), the safety of therapeutic anticoagulation is commonly questioned. A meta-analysis evaluated whether therapeutic anticoagulation is associated with an increased risk of ICH in patients with brain tumors. The results indicate that anticoagulation was not associated with an increased risk of ICH in brain metastasis. Still, it resulted in a greater than threefold increased risk of ICH in patients with glioma .
Another meta-analysis compared the risk of ICH between subjects with primary malignant neoplasms of the brain, diagnosed with VTE and treated with full‐dose anticoagulant therapy, to that in subjects with malignant glioma without VTE and not taking anticoagulant therapy. The results indicated that anticoagulation for VTE increases ICH risk in subjects with malignant brain tumors .
These results indicate that patients with brain tumors need greater caution when treated with anticoagulants.
In conclusion, there remain important issues that need further study regarding anticoagulant therapy in some specific subpopulations of patients.
Particular consideration should be considered when treating VTE in patients with a brain tumor or brain metastasis (because little evidence is available), patients with thrombocytopenia, severe renal or liver failure, history of bleeding, and unsuspected VTE.
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