VTE Prophylaxis
Aina Abell
In October 2019, FDA approved rivaroxaban (Xarelto—Janssen) for venous thromboembolism (VTE) prophylaxis in acutely ill hospitalized patients at risk of forming blood clots but not at high risk of bleeding. The agency’s approval of the direct oral anticoagulant (DOAC) provides an alternative oral option to low-molecular-weight heparins (LMWH) such as enoxaparin, which are the standard treatment and are typically administered as S.C. injections.
Supporting clinical evidence
Rivaroxaban’s approval was based on two Phase III clinical trials, MAGELLAN and MARINER, that evaluated more than 20,000 patients with acute medical illnesses.
MAGELLAN demonstrated that rivaroxaban was not inferior to enoxaparin for short-term VTE prophylaxis (around 10 days). It also revealed that rivaroxaban had superior outcomes in long-term use (around 35 days) compared with the recommended treatment of short-term, inpatient use of enoxaparin followed by no extended outpatient prophylaxis.
In addition, MARINER showed that use of rivaroxaban did not change VTE and VTE-related deaths compared with placebo. However, rivaroxaban did significantly reduce symptomatic VTE and had a favorable safety profile.
Both trials showed that patients taking rivaroxaban experienced higher rates of major and nonmajor bleeding.
With this FDA approval, rivaroxaban joins betrixaban (Bevyxxa—Portola), another DOAC, as an alternative method for VTE prophylaxis in adult patients who are hospitalized for acute medical illness and are at risk for developing blood clots and related complications. Betrixaban became the first DOAC approved for this indication in June 2017.
What do the guidelines say?
While DOACs such as rivaroxaban and betrixaban may be beneficial for preventing VTE in acutely ill hospitalized patients, the American Society of Hematology’s 2018 guideline for VTE prophylaxis for hospitalized and nonhospitalized medical patients continues to recommend LMWH such as enoxaparin, followed by fondaparinux and unfractionated heparin, as the preferred treatment.
The guideline also recommends inpatient prophylaxis with LMWH only and advises against extended prophylaxis with DOACs upon hospital discharge.
The recommendations were based on a systematic review of current evidence, which determined that while DOACs may have benefits, the drugs posed an increased risk of bleeding in acutely ill patients.
This increased risk was seen in both the inpatient and extended outpatient settings.
The guideline noted, however, that further research is necessary to evaluate the benefits and risks of using DOACs for short-term inpatient prophylaxis as well as extended outpatient prophylaxis upon discharge.
Things to consider
Given the most current recommendations, pharmacists should exercise caution and use clinical judgment when considering the use of DOACs in acutely ill hospitalized patients. DOACs may be appropriate in cases where an oral product is preferred. These may include patients who need continued prophylaxis after hospital discharge and are uncomfortable or unable to self-administer injections.
Pharmacists may also consider using rivaroxaban or betrixaban depending on the specific needs of the patient, said Joey Sweeney, PharmD, BCPS, director of pharmacy at Aurora Medical Center in Burlington, WI. Such situations may include patients who are hypersensitive to enoxaparin or cannot ingest porcine products because of hypersensitivity or religious beliefs, he said.
Decisions may also come down to cost, Sweeney added.
In a study published in the May 2019 issue of Pharmacoeconomics, Guy and colleagues revealed that betrixaban may be more cost-effective than enoxaparin in treating nonsurgical acutely ill patients who require longer prophylaxis from hospitalization through discharge. Betrixaban “dominated” enoxaparin both in cost and patient outcome, resulting in savings of $784 and increased quality-adjusted life-years of 0.17 per patient, wrote the authors.
Another study, a 2018 meta-analysis by Bhalla and colleagues published in the American Journal of Cardiology, showed that DOACs were noninferior to enoxaparin in efficacy, safety, and cost for short-term VTE prophylaxis among patients hospitalized for medical illness.
Patients at high risk for bleeding or experiencing active bleeding should not take rivaroxaban or betrixaban. Pharmacists should consider individual patients’ benefit–risk profile when making decisions on appropriate VTE prophylaxis treatment.