Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer.pptx

Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer

1. Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer

2. Importance Patients with cancer have up to a 7-fold excess risk of VTE. Practice guidelines recommend that patients with cancer and VTE receive treatment with LMWH rather than warfarin. Between 2012 and 2015, 4 DOACs, were approved by FDA for treatment of VTE and demonstrated similar efficacy and safety compared with warfarin in some cases. This study used a pragmatic design in which patients and physicians selected treatment either from among DOACs or from among LMWH or fondaparinaux .

3. Methods Eligibility Criteria Adults aged 18 years or older with solid tumors, lymphoma, chronic lymphocytic leukemia, or multiple myeloma were eligible if they had advanced disease or were diagnosed within the past 12 months.  Patients with either symptomatic or asymptomatic VTE detected on imaging studies within 30 days prior to enrollment were eligible regardless of the type of anticoagulant initiated prior to enrollment.  Additional eligibility criteria were: a platelet count of 50000/ μL or greater a creatinine clearance of 15 mL/min/1.75 or greater within 7 days of enrollment.   

4. Methods Exclusion criteria included: Acute leukemia, recent or planned stem cell transplant, Ongoing clinically significant bleeding, pregnancy or breastfeeding, use of medications that interfered with DOAC metabolism, life expectancy of less than 3 months, or receipt of therapeutic anticoagulation at the time the new VTE was diagnosed.

5. Methods

6. Results Primary Outcome: Recurrent VTE At final analysis on February 22, 2021, recurrent VTE had occurred in 6.1% of participants treated with a DOAC and 8.8% of participants treated with LMWH

7. Results Secondary Outcomes Bleeding Major bleeding occurred in 5.2% of the DOAC group and 5.6% of the LMWH group, which did not meet the prespecified criterion for noninferiority . Clinically significant nonmajor bleeding occurred in 5.8 % of the DOAC group and 2.6% of the LMWH group. Minor bleeding occurred in 8.0% of the DOAC group and 11.4% of the LMWH group. Death At 6 months, death occurred in 21.5 % of patients in the DOAC group and 18.4 % in the LMWH group.

8. Results Other Prespecified Outcomes At 3 months, 82.1% of participants randomized to DOACs and 72.7% of those randomized to LMWH continued to take their assigned treatment. At 6 months, 70.9% and 59.4% of participants assigned to DOACs and LMWH, respectively, were still taking their assigned anticoagulant. Of those assigned to LMWH, 6 % ( 20/338) transitioned to warfarin therapy.

9. Results Adverse Events Adverse events including VTE and bleeding occurred in 36.0% of participants assigned to DOACs and 38.7% assigned to LMWH. Rates of severe adverse events were 33.8 % in the DOAC group and 35.1% in the LMWH group. The most common severe adverse event was death (21.5% in the DOAC group and 18.4% in the LMWH group ). Other severe adverse events included: anemia of grade 3 or higher

10. Discussion This pragmatic, unblinded , comparative effectiveness trial of patients with cancer and acute VTE found that 6 months of DOAC therapy was noninferior to LMWH therapy for preventing VTE recurrence. Rates of major bleeding and death were not significantly different between groups. Compared with patients randomized to LMWH, 11% more patients were taking their assigned treatment in the DOAC group at 6 months.

11. Discussion Compared with prior trials, this study was an effectiveness trial that enrolled patients with borderline low platelet counts, brain metastases, and limited functional status. In previous efficacy trials, rates of major bleeding were significantly higher for foredoxaban or rivaroxaban compared with dalteparin but not for apixaban compared with dalteparin . The use of apixaban by almost 58.5% of participants randomized to the DOAC group may explain the lack of difference in major bleeding between the DOAC and LMWH groups, since apixaban is associated with lower bleeding rates than other DOACs.

12. Disscussion Although the bleeding rates in this trial were higher than those observed for DOAC treatment of VTE in the general population, they were similar to results from studies of anticoagulant therapy in patients with cancer-associated VTE. Consistent with prior clinical trials, results showed that patients treated with DOACs have a higher risk of clinically relevant nonmajor bleeding compared with patients treated with LMWH. Enrollment criteria were less stringent than in prior trials of DOAC therapy . Because patients with advanced cancer and brain metastases, impaired performance status, and reduced liver or kidney function were enrolled, results are likely to be more generalizable to patients encountered in oncology practice.

13. Limitations Participants and physicians were not blinded to treatment assignment Because participants were randomized within 30 days of a new VTE diagnosis, some were treated with different therapy before randomization. In patients with advanced-stage cancer, it was not possible to distinguish VTE from cancer as the cause of death. People of Asian race or Hispanic ethnicity were not well represented, and the proportion of participants who were Black was 13%, limiting the generalizability of results. Detailed medication adherence diaries were not obtained.

14. Conclusions Among adults with cancer and VTE, DOACs were noninferior to LMWHfor preventing recurrent VTE over 6-month followup . These findings support use of a DOAC to prevent recurrent VTE in patients with cancer.

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