Among medically ill hospitalized patients, extended-duration betrixaban significantly reduces the rate of any stroke compared with thromboprophylactic enoxaparin, according to findings from a phase 3 trial.
The results were presented by C. Michael Gibson, MD, of the Beth Israel Deaconess Medical Center, at the Scientific Sessions of the American Heart Association held November 12 to 16, 2016, in New Orleans, LA. Adrian F. Hernandez, MD, of Duke, was also involved in the research.
Stroke, including intracranial hemorrhage, can be a major complication for patients hospitalized for medical conditions, and it portends less-favorable outcomes than community-onset stroke. However, little is known about the effectiveness of novel oral anticoagulants for the prevention of stroke in this setting.
Researchers sought to add to this knowledge by conducting a retrospective substudy of data from the Acute Medically Ill VTE Prevention With Extended Duration Betrixaban (APEX) trial to evaluate the efficacy of extended-duration betrixaban compared with standard thromboprophylactic enoxaparin in reducing stroke among medically ill hospitalized patients.
The APEX trial was designed to evaluate whether extended-duration betrixaban, an oral factor Xa inhibitor, would reduce the incidence of all symptomatic venous thromboembolic (VTE) events compared with standard-duration enoxaparin. The findings of that study were published in the August 11, 2016, issue of the New England Journal of Medicine.
Betrixaban 80 mg is considered safe and effective on the basis of the results of phase 1 and 2 studies, so it was used in the APEX trial. The dosages for betrixaban and enoxaparin were halved for patients with renal insufficiency and a creatinine clearance rate of less than 30 mL/minute and for those receiving concomitant strong P-glycoprotein inhibitors.
The patients were considered to be at high risk for VTE and were hospitalized for a variety of reasons, the most common of which was New York Heart Association functional classification III/IV heart failure (HF; approximately 44%); approximately 11% of patients were admitted to the hospital for acute ischemic stroke.
The patients were randomly assigned in a double-blind fashion to either oral betrixaban for an extended duration (35 days; n = 3,759) or subcutaneous enoxaparin for a standard duration (10 ± 4 days; n = 3,754).
Betrixaban was associated with a 24% relative risk reduction in the primary end point, which was a composite of asymptomatic proximal deep venous thrombosis, symptomatic proximal or distal deep venous thrombosis, nonfatal pulmonary embolus, or VTE-related death (7.0% for enoxaparin vs 5.3% for betrixaban; P = .006).
The data also revealed that betrixaban significantly reduced the rate of any stroke in the modified intent-to-treat population (Table).
Table. Rate of Stroke in the Modified ITT Population
(n = 2,991),
(n = 2,986),
|Any||30 (1.00)||14 (0.47)||0.53 (0.12 to 0.75)||.016|
|Ischemic||28 (0.94)||13 (0.44)||0.53 (0.10 to 0.76)||.019|
|Hemorrhagic||1 (0.03)||0 (0.00)||—||—|
|Uncertain||1 (0.03)||1 (0.03)||0.00 (–15.01 to 0.94)||.999|
|TIA||5 (0.17)||3 (0.10)||0.40 (–1.51 to 0.86)||.86|
|Any stroke or TIA||35 (1.17)||17 (0.57)||0.51 (0.13 to 0.73)||.012|
CI = confidence interval, ITT = intent to treat, TIA = transient ischemic attack.
For the study patients who received a reduced dose of betrixaban, no significant differences were observed in the rates of stroke between the 2 groups. Among the patients at highest risk, in those with a history of atrial fibrillation, ischemic stroke, or HF as the index event, betrixaban significantly reduced the rate of any stroke (1.44% vs 0.69%; relative risk reduction 0.52 [0.12-0.74]; P = .015) and the rate of ischemic stroke (1.35% vs 0.59%; relative risk reduction 0.56 [0.16-0.77]; P = .011).
The 2 drugs were not significantly different with regard to the primary safety end point of major bleeding (0.57% vs 0.67%; P = .55). Betrixaban was associated with a higher rate of major or clinically relevant non–major bleeding events (1.59% vs 3.12%; P < .001); however, the rate of fatal bleeding was the same for both drugs (1 in each group). Fewer cases of intracranial hemorrhage were observed in the betrixaban than in the enoxaparin group (7 vs 2), but the difference was not significant (P = .18).
The researchers hope the findings will help address an unmet need for extended thromboprophylaxis in this patient population.
Source: Gibson CM, Daaboul Y, Korjian S, et al. Extended duration betrixaban reduces the risk of stroke vs standard dose enoxaparin among hospitalized medically ill patients: an APEX substudy. Presented at: American Heart Association Scientific Sessions 2016; November 12-16, 2016; New Orleans, LA. Abstract 277.