Study findings suggest that extended-duration betrixaban reduces the first and total number of symptomatic venous thromboembolic (VTE) events vs standard-dose enoxaparin among medically ill hospitalized patients. The treatment addresses an unmet need for extended thromboprophylaxis in acutely ill patients.
VTE occurs in approximately 8 million acutely ill patients each year in the United States, despite the available standard-of-care agents. Approximately 1 of 2 deep venous thromboses (DVTs) and pulmonary emboli (PEs) occur within 6 weeks after hospital discharge, a time period for which no agents are currently approved or guideline-recommended for thromboprophylaxis.
Purva Jain, MPH, of the Beth Israel Deaconess Medical Center, presented the results of the study at the Scientific Sessions of the American Heart Association held November 12 to 16, 2016, in New Orleans, LA. The study was a substudy of the Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study (APEX).
“The reduction of the total burden of symptomatic VTE events among patients taking betrixaban may reduce the use of health care resources and alleviate costs related to inpatient and outpatient care and pharmacy use,” said Jain.
Jain provided a brief overview of APEX, which was a phase 3 trial designed to evaluate whether the incidence of all symptomatic VTE events, including those that occur after the first event, would be reduced by extended-duration betrixaban compared with standard-duration enoxaparin. The results of that study were published in the August 11, 2016, issue of the New England Journal of Medicine.
The participants in that trial were considered to be at high risk for VTE and were randomly assigned in a double-blind fashion to either oral betrixaban for an extended duration (35 days) or subcutaneous enoxaparin for a standard duration (10 ± 4 days).
The primary efficacy end point of APEX was a composite of asymptomatic proximal DVT, symptomatic proximal or distal DVT, nonfatal PE, or VTE-related death.
Betrixaban was associated with a 24% relative risk reduction in the primary end point (7.03% for enoxaparin vs 5.30% for betrixaban; P = .006). The treatments were not significantly different in terms of the primary safety end point, which was major bleeding through 7 days after drug discontinuation (0.57% vs 0.67%, respectively; P = .55).
In discussing the results of the substudy, Jain noted that the evaluation of multiple thrombotic events is important because recurrent VTEs are associated with worse clinical outcomes and a significantly greater total cost of care.
She also reported that fewer patients in the betrixaban arm had multiple events throughout the trial compared with the enoxaparin arm (1 vs 6, respectively; P = .07). Compared with standard-duration enoxaparin, extended-duration betrixaban was associated with a 31% to 48% relative reduction in the risk of multiple VTEs.
The time to multiple symptomatic events (through the last day of contact) was significantly lower in the betrixaban arm than in the enoxaparin arm (Table).
Table. Time to Multiple Symptomatic Event Through Last Day of Contact
|Event at End of
Active Treatment Period
|Betrixaban (n = 3,721), n (%)||Enoxaparin
(n = 3,720),
|End pointa||38 (1.0)||73 (2.0)||0.52 (0.35-0.79)||.002|
|DVT||14 (0.4)||25 (0.7)||0.56 (0.29-1.08)||.083|
|PE||9 (0.2)||22 (0.6)||0.41 (0.19-0.89)||.024|
|VTE||15 (0.4)||26 (0.7)||0.58 (0.31-1.09)||.092|
aComposite of asymptomatic proximal DVT, symptomatic proximal or distal DVT, nonfatal PE, or
CI = confidence interval, DVT = deep venous thrombosis, HR = hazard ratio, PE = pulmonary embolism, VTE = venous thromboembolism.
With regard to safety, no patients in either treatment arm had more than 1 major bleeding event. An excess of single minor or clinically relevant non–major bleeding events was observed in the betrixaban arm, but no significant difference was seen in terms of multiple minor or clinically relevant non–major bleeding events.
Source: Jain P, Szlosek DA, Korjian S, et al. Betrixaban reduces the burden of multiple symptomatic venous thromboembolic events in the APEX trial. Presented at: American Heart Association Scientific Sessions 2016; November 12-16, 2016; New Orleans, LA. Abstract 640.