DOAC Reversal and Use in Patients Recovered From COVID-19

Volume 11, Issue 1

Happy new year everyone! Welcome to the first installment of Talking Therapeutics for 2022.

In kicking off the new year, we’re going back to a familiar topic: anticoagulation in patients with COVID-19. This time, however, we’ll be looking at a new study using direct oral anticoagulants (DOACs) in patients who have recovered from COVID-19. This study is unique, as DOACs have not been previously studied in patients with COVID-19, and prior studies evaluating anticoagulation have focused exclusively on hospitalized patients (rather than survivors who have been discharged).

We’ll also look at a new study evaluating how long to hold apixaban prior to planned surgeries.

Point #1: Extended VTE Prophylaxis Has Promise in Patients who Recovered From COVID-19

Prior studies have established the heightened risk of venous thromboembolic (VTE) events in patients with COVID-19, and research has explored the use of anticoagulation for those admitted to hospital. This week, a new study was published looking at extended VTE prophylaxis for patients with COVID-19 discharged from the hospital. The MICHELLE trial was a multicenter, randomized, controlled trial conducted at 14 hospitals in Brazil. The objective was to assess whether rivaroxaban 10 mg/day for 35 days, initiated at hospital discharge, reduced the risk of future VTE.

Eligible patients were admitted with COVID-19 and had increased risk for VTE (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL).

The primary efficacy outcome was “a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35.” Among 159 patients assigned to each treatment group, this outcome occurred in 5 patients (3%) receiving rivaroxaban and 15 patients (9%) receiving no anticoagulation (relative risk .33, 95% CI .12–.90; P=.0293). Authors added that no major bleeding occurred in either group. 

This trial adds to the growing body of literature supporting short-term DOAC use in at-risk nonsurgical patients discharged from the hospital. Betrixaban and rivaroxaban, for instance, already have indications for extended prophylaxis in acutely ill medical patients who are discharged from the hospital.

Point #2: Hold Apixaban for at Least Two Days Prior to Major Surgery

The ADIOS trial was a prospective, observational study in which researchers measured apixaban plasma concentration and anti-Xa activity in patients prior to surgery.

Study authors reported:

“Ninety-four percent (104 of 111) of patients had measured apixaban concentrations of ≤30 ng/mL. The median time between the self-reported last dose and presurgery blood sampling was 76 hours (range 32-158) for those who achieved concentrations ≤30 ng/mL and 59 hours (range 49-86) for those >30 ng/mL. Clinically significant nonmajor bleeding was reported in one patient at 1 week postsurgery. There was one venous thromboembolic event and one stroke in the perioperative period.”

While prior clinical trials confirmed that 48 hours is the appropriate threshold for holding apixaban prior to major surgery, this study confirms these findings in a real-world setting in a heterogeneous patient population.