Rates of bleeding, VTE remain low after 1-year edoxaban in real world

The overall rates of bleeding and recurrent venous thromboembolism (VTE) were low across various subgroups after 12 months of edoxaban treatment in routine clinical practice, according to a non-interventional, post-authorization safety study of edoxaban — ETNA-VTE* presented during the ISTH 2020 Meeting.

In a global subanalysis stratifying patients by age, there was no significant association between increasing age and recurrent VTE — indicating that edoxaban treatment for VTE was effective across all age groups in routine clinical practice. [ISTH 2020, abstract PB2409]

On the other hand, the rates of major bleeding and all-cause mortality rose with advancing age, although the deaths were not driven by cardiovascular cause.

“These real-world findings provide clinicians with additional evidence of edoxaban’s safety in specific VTE patient populations that are considered high-risk for bleeding, recurrent VTE or other cardiovascular events, or who have comorbidities,” said principal investigator Dr Alexander Cohen from Guy’s and St Thomas’ Hospital at King’s College London, UK.

“This is of particular significance for ageing patients and those who treat them, as the elderly are at greatest risk due to the high prevalence of predisposing comorbidities and acute illnesses, making edoxaban a viable treatment option for this population,” he added.

Participants in the subanalysis were 3,908 patients (mean age, 64.9 years) in the global ETNA-VTE programme who initiated treatment with edoxaban for VTE as part of routine clinical care. About one-third of the participants were aged ≥75 years old (32.7 percent) while 43.3 percent of them were ≤65 years.

Over 12 months of follow-up, the rates of VTE recurrence trended lower with increasing age: reported in 3.65 percent of patients aged <65 years, 2.83 percent of those aged between 65 –74 years, 2.3 percent of those aged between 75–84 years, and 3.07 percent of patients aged ≥85 years.

The rates of major bleeding events, as defined by the ISTH criteria, were 1.34 percent in the subgroup aged <65 years, 3.16 percent in the age 65–74 subgroup, 2.97 percent in the age 75–84 subgroup, and 5.72 percent in the subgroup aged ≥85 years.

As expected, all-cause mortality also trended higher with increasing age — occurring in 3.61 percent, 6.28 percent, and 9.63 percent of patients in the subgroup aged <65, 65–74, and ≥75 years, respectively. However, this was not driven by cardiovascular-related mortality, which occurred in 0.47 percent, 1.28 percent, and 2.03 percent of the patients, respectively. 

“VTE recurrences occurred less frequently and bleeding occurred more frequently in older patients,” the researchers reported.

In another subanalysis stratified by thrombotic risk factors, the researchers found that VTE recurrence was more common in patients with active cancer than those without (17 percent vs 12 percent). [ISTH 2020, abstract PB/LB02]  

Reversible provoking risk factors, such as major surgery or trauma, prolonged bed rest (5-7 days), and puerperium, were also associated with a higher incidence of VTE recurrence (28 percent vs 21 percent).

Compared with patients without VTE recurrence, those who had recurrent VTE were more likely to be younger (62.7 vs 65 years), had major bleeding (annualized event rates, 5.6 vs 2.4 percent/year), clinically relevant nonmajor bleeding (6.6 vs 3.5 percent/year), and all-cause mortality (11 vs 5 percent/year).

“[Nonetheless,] the 12-month recurrence rate of VTE was [considered] low in patients receiving edoxaban, overall and by risk subgroups,” concluded Cohen.