Hospital Pharmacy - February 2018 - 31
31
Baker
not required before administering rivaroxaban or apixaban. If a decision is made to extend treatment in VTE
patients with risk factors for recurrence, the direct oral
anticoagulants are effective in reducing the incidence of
recurrent VTE; the same anticoagulant used for long-term
treatment should be used for extended-duration treatment
unless patient circumstances warrant a change in anticoagulant therapy. Betrixaban was not available when these
guidelines were created.
Studies
Drug: Betrixaban versus Enoxaparin
Reference: Cohen AT, et al 2014; Cohen AT, et al 2016
(APEX trial)1,12,13
Study Design: Randomized, double-blind, doubledummy, active-controlled, multicenter, international study
Study Funding: Portola Pharmaceuticals
Patients: 7,513 patients 40 years and older hospitalized
for a specified acute medical illness (eg, heart failure,
infectious disease, respiratory failure, rheumatic disease,
ischemic stroke) and who had additional risk factors for
VTE were expected to be severely immobilized for 24
hours during hospitalization and moderately and/or
severely immobilized for at least 4 days after study enrollment, and had an anticipated survival of at least 8 weeks.
Key exclusion criteria included hospitalization for more
than 96 hours prior to randomization; inability to take
enteral feeding; increased risk of bleeding or history of
intracranial bleeding; need for major surgery or invasive
procedure; contraindications to anticoagulant therapy;
and elevated liver function tests, active liver disease, or
cirrhosis. Average patient age was approximately 76
years, with approximately 68% of patients aged 75 years
or older; 45% were male; 93% were white; mean weight
was approximately 80 kg; body mass index was approximately 29.4 kg/m2; and median duration of hospitalization was 10 days. Two cohorts were established within the
overall population: Cohort 1 included patients with elevated baseline d-dimer level at least 2 times the upper
limit of normal (n = 3870), and cohort 2 included patients
meeting criteria for cohort 1 plus those 75 years of age
and older (n = 5735). The overall study population cohort
included patients from cohorts 1 and 2 who were included
in the primary efficacy outcome analysis (n = 6286).
Intervention: Patients were randomized (1:1) to receive
oral betrixaban plus subcutaneous enoxaparin placebo or
subcutaneous enoxaparin plus oral betrixaban placebo
using a double-blind, double-dummy design. On day 1,
all patients received 2 capsules of either betrixaban 80
mg or placebo orally, followed by one 80-mg capsule
orally once daily for the remainder of the study (35-42
days). Patients receiving a concomitant strong
P-glycoprotein (P-gp) inhibitor or who had severe renal
insufficiency (creatinine clearance [CrCl] more than 15
mL/min and less than 30 mL/min) received a reduced
dose of betrixaban 80 mg initially and 40 mg once daily
thereafter. Enoxaparin (or matching placebo) was administered at a dose of 40 mg subcutaneously daily for 6 to
14 days (patients with CrCl more than 15 mL/min and
less than 30 mL/min received enoxaparin 20 mg). The
median duration of treatment was 36 days in the betrixaban group and 9 days in the enoxaparin group.
Results
Primary End Point(s)
** Composite of asymptomatic proximal DVT between
days 32 and 47, symptomatic proximal or distal DVT,
symptomatic nonfatal PE, or death from VTE between
days 1 and 42:
|| Cohort 1: 6.9% of patients in the betrixaban group
and 8.5% in the enoxaparin group (relative risk
[RR], 0.81; 95% confidence interval [CI], 0.65-1;
P = .054).
|| Cohort 2: 5.6% of patients in the betrixaban group
and 7.1% in the enoxaparin group (RR, 0.8; 95%
CI, 0.66-0.98; P = .03).
|| Overall population cohort: 5.3% of patients in the
betrixaban group and 7% in the enoxaparin group
(RR, 0.76; 95% CI, 0.63-0.92; P = .006).
** In the overall safety population (n = 7432), major
bleeding at any point up to 7 days after discontinuation occurred in 0.7% of the betrixaban group and
0.6% of the enoxaparin group (RR, 1.19; 95% CI,
0.67-2.12; P = .55).
Secondary End Point(s)
** Composite of symptomatic VTE through day 42
(death from VTE, nonfatal PE, or symptomatic DVT)
occurred in 0.9% of patients in the betrixaban group
and 1.5% in the enoxaparin group (RR, 0.64; 95% CI,
0.42-0.98; P = .04).
** Composite of primary efficacy outcome plus death
from any cause (instead of death from VTE) for the
overall population changed to an occurrence of 9.2%
in the betrixaban group and 10.8% in the enoxaparin
group (RR, 0.85; 95% CI, 0.73-0.98; P = .02).
** Net clinical benefit (composite of the primary efficacy
outcome and the primary safety outcome) occurred in
5.8% of the betrixaban group and 7.3% of the enoxaparin group (RR, 0.78; 95% CI, 0.65-0.95; P = .01).
** Major or clinically relevant nonmajor bleeding occurred
in 3.1% of the betrixaban group and 1.6% of the enoxaparin group (RR, 1.97; 95% CI, 1.44-2.68; P < .001).
** New ischemic stroke occurred in 0.5% of patients in
the betrixaban group and 0.9% in the enoxaparin
group (RR, 0.53; 95% CI, 0.3-0.94; P = .03). Incidence
for the development of any type of stroke was 0.6% in
Table of Contents for the Digital Edition of Hospital Pharmacy - February 2018
Ed Board
TOC
Editorial
The Evolving Frontier of Digital Health: Opportunities for Pharmacists on the Horizon
Letter to the Editor
Immediate Attention Required: Another Shortage
ISMP Adverse Drug Reactions
ISMP Adverse Drug Reactions
Current FDA-Related Drug Information
Summaries of Safety Labeling Changes Approved By FDA: Boxed Warnings Highlights July-September 2017
ISMP Medication Error Report Analysis
Common Missteps With Medication Safety: Rolling a Single Dice, Ineffective Strategies, and Unexecuted Action Plans
Formulary Drug Reviews
Betrixaban
Pharmaceutical Pipeline Update
Antibiotics in Development for the Treatment of Resistant Bacterial Disease
Articles
Evaluation of the Incidence of Ibuprofen Administration in Alcohol and Opioid Detoxification Patients With Concomitant Thrombocytopenia
Antimicrobial Utilization Pattern in Pediatric Patients in Tertiary Care Hospital, Eastern Ethiopia: The Need for Antimicrobial Stewardship
Acute Hepatocellular Jaundice After Dofetilide Initiation: A Case Report
Outcomes From a Pharmacist: Led Proton Pump Inhibitor Stewardship Program at a Single Institution
Corrigendum
Hospital Pharmacy - February 2018 - Cover1
Hospital Pharmacy - February 2018 - Cover2
Hospital Pharmacy - February 2018 - 1
Hospital Pharmacy - February 2018 - 2
Hospital Pharmacy - February 2018 - 3
Hospital Pharmacy - February 2018 - Ed Board
Hospital Pharmacy - February 2018 - TOC
Hospital Pharmacy - February 2018 - Editorial
Hospital Pharmacy - February 2018 - The Evolving Frontier of Digital Health: Opportunities for Pharmacists on the Horizon
Hospital Pharmacy - February 2018 - 8
Hospital Pharmacy - February 2018 - 9
Hospital Pharmacy - February 2018 - 10
Hospital Pharmacy - February 2018 - Letter to the Editor
Hospital Pharmacy - February 2018 - Immediate Attention Required: Another Shortage
Hospital Pharmacy - February 2018 - 13
Hospital Pharmacy - February 2018 - ISMP Adverse Drug Reactions
Hospital Pharmacy - February 2018 - ISMP Adverse Drug Reactions
Hospital Pharmacy - February 2018 - 16
Hospital Pharmacy - February 2018 - Current FDA-Related Drug Information
Hospital Pharmacy - February 2018 - Summaries of Safety Labeling Changes Approved By FDA: Boxed Warnings Highlights July-September 2017
Hospital Pharmacy - February 2018 - 19
Hospital Pharmacy - February 2018 - 20
Hospital Pharmacy - February 2018 - 21
Hospital Pharmacy - February 2018 - 22
Hospital Pharmacy - February 2018 - 23
Hospital Pharmacy - February 2018 - ISMP Medication Error Report Analysis
Hospital Pharmacy - February 2018 - Common Missteps With Medication Safety: Rolling a Single Dice, Ineffective Strategies, and Unexecuted Action Plans
Hospital Pharmacy - February 2018 - 26
Hospital Pharmacy - February 2018 - 27
Hospital Pharmacy - February 2018 - Formulary Drug Reviews
Hospital Pharmacy - February 2018 - Betrixaban
Hospital Pharmacy - February 2018 - 30
Hospital Pharmacy - February 2018 - 31
Hospital Pharmacy - February 2018 - 32
Hospital Pharmacy - February 2018 - 33
Hospital Pharmacy - February 2018 - 34
Hospital Pharmacy - February 2018 - 35
Hospital Pharmacy - February 2018 - 36
Hospital Pharmacy - February 2018 - Pharmaceutical Pipeline Update
Hospital Pharmacy - February 2018 - Antibiotics in Development for the Treatment of Resistant Bacterial Disease
Hospital Pharmacy - February 2018 - 39
Hospital Pharmacy - February 2018 - Articles
Hospital Pharmacy - February 2018 - Evaluation of the Incidence of Ibuprofen Administration in Alcohol and Opioid Detoxification Patients With Concomitant Thrombocytopenia
Hospital Pharmacy - February 2018 - 42
Hospital Pharmacy - February 2018 - 43
Hospital Pharmacy - February 2018 - Antimicrobial Utilization Pattern in Pediatric Patients in Tertiary Care Hospital, Eastern Ethiopia: The Need for Antimicrobial Stewardship
Hospital Pharmacy - February 2018 - 45
Hospital Pharmacy - February 2018 - 46
Hospital Pharmacy - February 2018 - 47
Hospital Pharmacy - February 2018 - 48
Hospital Pharmacy - February 2018 - 49
Hospital Pharmacy - February 2018 - 50
Hospital Pharmacy - February 2018 - 51
Hospital Pharmacy - February 2018 - 52
Hospital Pharmacy - February 2018 - 53
Hospital Pharmacy - February 2018 - 54
Hospital Pharmacy - February 2018 - Acute Hepatocellular Jaundice After Dofetilide Initiation: A Case Report
Hospital Pharmacy - February 2018 - 56
Hospital Pharmacy - February 2018 - 57
Hospital Pharmacy - February 2018 - 58
Hospital Pharmacy - February 2018 - Outcomes From a Pharmacist: Led Proton Pump Inhibitor Stewardship Program at a Single Institution
Hospital Pharmacy - February 2018 - 60
Hospital Pharmacy - February 2018 - 61
Hospital Pharmacy - February 2018 - 62
Hospital Pharmacy - February 2018 - 63
Hospital Pharmacy - February 2018 - 64
Hospital Pharmacy - February 2018 - 65
Hospital Pharmacy - February 2018 - 66
Hospital Pharmacy - February 2018 - 67
Hospital Pharmacy - February 2018 - Corrigendum
Hospital Pharmacy - February 2018 - Cover3
Hospital Pharmacy - February 2018 - Cover4
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