Reduction of Cardiovascular Mortality and Ischemic Events in Acute Medically Ill Patients
Authors: Tarek Nafee, C. Michael Gibson, Megan K. Yee, Mathieu Kerneis, Yazan Daaboul, Serge Korjian, Gerald Chi, Arzu Kalayci, M. Khurram Afzal, Hassan Kazmi, Sudarshana Datta, Fahad AlKhalfan, Adrian F. Hernandez, Russell D. Hull, Robert A. Harrington, Alexander T. Cohen, Samuel Z. Goldhaber
Journal: Circulation (2019)

◼ factor Xa inhibitors ◼ preventive care T he efficacy of extended prophylaxis with betrixaban for 35 to 42 days has been evaluated in the randomized, multicenter, phase III APEX trial (Acute Medically Ill VTE Prevention with Extended Duration Betrixaban; n=7513; Clinical Trial Registration: URL: https://www.clinicaltrials.gov;Unique identifier: NCT01583218).Betrixaban reduced the risk of venous thromboembolism (VTE) in comparison with enoxaparin and reduced the incidence of stroke.This post hoc study of the APEX trial evaluates the effect of betrixaban, in comparison with enoxaparin, on the incidence of major adverse cardiovascular events (MACE).The study design and primary results of the APEX trial were previously published. 1The present post hoc study analyzed subjects included in the modified intention-to-treat population, which included all randomly assigned subjects who received ≥1 dose of study drug.A subset of the modified intention-to-treat population at high risk of MACE was analyzed and included subjects with an acute ischemic stroke at index hospitalization and subjects with a history of either myocardial infarction (MI) or nonhemorrhagic stroke (ie, ischemic or of uncertain etiology).The primary end point was the composite of MACE, including cardiovascular death, MI, or stroke.Individual components of the primary composite were also analyzed.All cardiovascular death and stroke events, but not MI events, were adjudicated by an independent, blinded clinical events committee.Analyses were completed at day 42, when the study drug was discontinued, and through the end of the follow-up period at day 77.The APEX trial was approved by an institutional review committee, and all subjects gave informed consent.Baseline characteristics and risk factors for MACE were well balanced between the 2 treatment arms.A total of 3243 (43.2%) had either an acute ischemic stroke as a diagnosis for the index hospitalization or a history of MI or stroke (n=1607 in the betrixaban group versus n=1636 in the enoxaparin group).Likewise, baseline characteristics were similar between the 2 treatment arms among the subset of high-risk subjects with a history of MACE and among those without a history of MACE.In comparison with enoxaparin, betrixaban was associated with a significant reduction in the primary end point of cardiovascular death, MI, or stroke at 42 days (2.4% [n=89] in the betrixaban group versus 3.5% [n=130] in the enoxaparin group; hazard ratio [HR], 0.69; 95% CI, 0.52-0.90;P=0.006; absolute risk reduction [ARR], 1.1%; number needed to treat [NNT], 91).When the analysis was extended through 77 days, the reduction in hazard with betrixaban remained unchanged (2.9% [n=104] in the betrixaban group versus 4.3% [n=153] in the enoxaparin group; HR, 0.68; 95% CI, 0.53-0.87;P=0.002; ARR, 1.4%; NNT, 72; Figure A).Through 42 days, cardiovascular death occurred in 2.0% (n=72) of the subjects in the betrixaban group and 2.7% (n=100) in the enoxaparin group (HR, 0.72; 95% CI, 0.53-0.98;P=0.034; ARR, 0.7%; NNT, 143).