Written by Peter Liu
Spoon Feed
Reduced-dose apixaban reduces risk of venous thromboembolism (VTE) for outpatients receiving chemotherapy for active cancer with high risk for VTE.
DOAC for outpatient oncologic VTE prophylaxis
The AVERT Trial for oncologic VTE prevention was a randomized, placebo-controlled, double-blind trial evaluating apixaban (2.5 mg twice daily) for venous thromboembolism (VTE) prophylaxis in ambulatory cancer patients initiating chemotherapy with a Khorana score ≥2 (high risk for VTE). Among 563 patients, VTE occurred in 4.2% of the apixaban group versus 10.2% in the placebo group (HR 0.41, 95%CI 0.26–0.65, P<0.001; NNT = 17). Major bleeding was higher with apixaban (3.5% vs. 1.8%, HR 2.00, 1.01–3.95, P=0.046; NNH = 59). These findings from AVERT, coupled with similar findings from the CASSINI Trial, have led to recent changes in ASCO Guidelines to recommend consideration of VTE prophylaxis for patients starting chemotherapy with Khorana score ≥ 2. It is important to note several nuances to this seemingly simple framework. First, adherence is likely to be an issue in many patients. For example, adherence to apixaban was 84% over 180 days in the ADOPT trial, and adherence to rivaroxaban in CASSINI was 56% over the same timeframe. Second, it is important to recognize that the Khorana score has limited predictive power, so some patients with high risk of VTE may be missed using this score, though there is not yet a clearly superior alternate risk-stratification framework. Finally, AVERT excluded patients with risk factors for bleeding, such as hepatic disease with coagulopathy, renal disease, high risk neoplasms such as acute leukemia, or thrombocytopenia. Decisions to use prophylaxis against VTE in these patients remains less certain.
How does this change my practice?
This study provides context to understand outpatient anticoagulation decisions in patients starting chemotherapy. The CASSINI and AVERT trials led to a paradigm shift away from vitamin K antagonists (warfarin) to DOACs. When I started my residency, we talked about the niches for which DOACs could be used v.s. warfarin. Now the paradigm has flipped, such that warfarin has only four indications: mechanical valves/ventricular assist device, moderate to severe mitral stenosis with atrial fibrillation, renal failure, and antiphospholipid antibody syndrome.
Source
Apixaban to Prevent Venous Thromboembolism in Patients with Cancer. N Engl J Med. 2019 Feb 21;380(8):711-719. doi: 10.1056/NEJMoa1814468. Epub 2018 Dec 4. PMID: 30511879
