Betrixaban (Bevyxxa) for extended duration VTE ppx

Betrixaban VTE ppx

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A New Standard for Extended-Duration VTE
Prophylaxis in Acutely Ill Medical Patients

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Disclosure
2
Today’s speaker is receiving compensation
from Portola Pharmaceuticals, Inc. for
presentation of this promotional program.
This program will not qualify for
Continuing Medical Education (CME)
credits.

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Presentation Overview
¡In-Hospital and Extended-Duration VTE Prophylaxis: The Unmet Need
¡Overview of Bevyxxa® (betrixaban) Safety and Efficacy
¡BevyxxaDosing and Administration
¡Summary
3
VTE=venous thromboembolism.

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In-Hospital and Extended-Duration VTE Prophylaxis in the
Acutely Ill Medical Population
4
The Unmet Need

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>8 Million
US hospitalized medical patients
at risk for VTE
~200,000
estimated VTE-related events
despite prophylaxis
40,000
estimated VTE deaths each year
VTE Is Prevalent in Acute Medical Patients:
200,000 VTEs and 40,000 VTE Related Deaths Occur Annually Despite Standard Prophylaxis
5
Piazza G et al. ThrombHaemost.2009;102(3):505-510.
41 year old, acute medically ill
patient with pulmonary embolism

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VTE Is Prevalent and Preventable in the Hospital
6
1. Geertset al. Chest.2008;133(6):381S-453S. 2. Cohen AT et al. BMJ. 2006;332(7537):325-329 . 3. Samamaet al. N EnglJ Med.1999;341(11):793-800. 4. GoldhaberSZ
et al. N EnglJ Med. 2011;365(23):2167-2177. 5. Cohen AT et al. N EnglJ Med. 2013;368(6):513-523.
0.0%
5.0%
10.0%
15.0%
20.0%
COMPOSITE VTE EVENT RATE
BASED ON CLINICAL TRIAL DATA
No VTE Prophylaxis1-3
With In-Hospital Enoxaparin VTE Prophylaxis
for 6 to 14 days2-5
VTE Rate (%) VTE Rate 2%-6%
ADOPT
VTE Rate 10%-20%
MAGELLANMEDENOX

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Increased Persistence of VTE Up to 35 Days Following
Discontinuation of Standard Duration Prophylaxis
7
Cohen AT et al. N EnglJ Med. 2013;368(6):513-523.
0.0%
5.0%
10.0%
VTE EVENTS AT DAY 35
Enoxaparin Standard Duration + Placebo
VTE Rate (%)
+110%
2.7%
5.7%
5-FOLD INCREASE IN VTE-RELATED MORTALITY BETWEEN DAY 10 AND DAY 35 (0.2% VS. 1.0%)
VTE EVENTS AT DAY 10
Enoxaparin Standard Duration
VTE EVENT RATE
FOLLOWING 6-14 DAYS IN-HOSPITAL PROPHYLAXIS WITH ENOXAPARIN

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VTE Risk Persists Post-Discharge After In-Hospital Prophylaxis
8
Amin AN et al. J Hosp Med. 2012;7(3):231-238
DAYS AFTER ADMISSION
Mean Hospital Stay
5.3 DAYS
CUMULATIVE 180
-DAY PROBABILITY (%)
2.5%
0
0 4020
0.5%
1.0%
1.5%
2.0%
70%
60%
50%
40%
30%
20%
10%
SYMPTOMATIC VTE RATE (%)
§Real-world analysis of US hospital database
(>11,000 patients)
§Greater than 2.0% symptomatic VTE event
rate through 40 days
§Majority of events occurred after hospital
discharge and standard prophylaxis
§Less than 10% of patients received
pharmacologic VTE prophylaxis post-discharge
SYMPTOMATIC VTE IN
ACUTE MEDICAL PATIENTS

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Underlying Comorbidities and Prevalent Risk Factors Identify
Medical Patients at Extended Risk for VTE
9
1. Cohen AT et al. Lancet. 2008;371(9610):387-394. 2.Piazza G et al. Thromb Haemost. 2009;102(3):505-510. 3. Cohen et al. Poster presented at: ISTH 2017. 4. Clark C et al. Poster
presented at: ISTH 2017: July 8-13 2017.5. Schleyer AM, et al. Am J Med Qual. 2011;26(3):174-80.
ACUTE MEDICAL PATIENTS AT HIGH VTE RISK1
SUBSET OF ACUTE MEDICAL
PATIENTS AT EXTENDEDVTE RISK
4.8 -5.2 MILLION
BASED ON REAL-WORLD STUDIES
21%
46%
19%
11% 5%
HEART FAILUREINFECTIONRESPIRATORY
FAILURE
ISCHEMIC
STROKE
RHEUMATIC
DISEASE
AdditionalRisk Factors% of
Patients
Age ≥ 75 years3 41%
D-dimer ≥ 2x ULN4 49%
ICU/CCU admission1 28%
Previous VTE5 16%
History of cancer5 21%
Obesity5 13%
Chronic venous insufficiency17%
~ 8 MILLION
PER ACCP GUIDELINES2

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OVERALL VTE MAJOR BLEEDING
Prior to Bevyxxa® (betrixaban) Approval, Clinical Studies Demonstrated That In-Hospital and
Post-Discharge VTE Is Preventable But With A Penalty of Increased Major Bleeding
10
1. Hull RD et al. Ann Intern Med. 2010;153(1):8-18. 2.GoldhaberSZ et al. N EnglJ Med. 2011;365(23):2167-2177. 3. Cohen AT et al. N EnglJ Med. 2013;368(6):513-523.
EXCLAIM1
Post-discharge enoxaparin vs placebo
ADOPT2
Apixaban(30 days) vs enoxaparin*/placebo
È
REDUCED VTE†
2.5% vs 4.0%, P<0.042
≈
MARGINAL REDUCTION
2.7% vs 3.1%, P=0.44
Ç
INCREASED BLEEDING
0.8% vs 0.3%, P<0.050
Ç
INCREASED BLEEDING
0.5% vs 0.2%, P=0.04
MAGELLAN3
Rivaroxaban (35±4 days) vs enoxaparin*/placeboÈ
REDUCED VTE
4.4% vs 5.7%, P=0.02
Ç
INCREASED BLEEDING
1.1% vs 0.4%, P<0.001
*Enoxaparin treatment duration: 6-14 days. † Failed interim futility analysis for efficacy

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Overview of Bevyxxa®(betrixaban) and the APEX Clinical Trial
11

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Indications and Usage
12
BETRIXABAN IS INDICATED FOR THE PROPHYLAXIS OF VENOUS THROMBOEMBOLISM
(VTE) IN ADULT PATIENTS HOSPITALIZED FOR AN ACUTE MEDICAL ILLNESSWHO ARE
AT RISK FOR THROMBOEMBOLIC COMPLICATIONS DUE TO MODERATE OR SEVERE
RESTRICTED MOBILITY AND OTHER RISK FACTORS FOR VTE
LIMITATIONS OF USE
THE SAFETY AND EFFECTIVENESS OF BEVYXXAHAVE NOT BEEN ESTABLISHED IN
PATIENTS WITH PROSTHETIC HEART VALVES BECAUSE THIS POPULATION
HAS NOT BEEN STUDIED

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Boxed Warning
13
WARNING: SPINAL/EPIDURAL HEMATOMA
EPIDURAL OR SPINAL HEMATOMAS MAY OCCUR IN PATIENTS TREATED WITH
BETRIXABAN WHO ARE RECEIVING NEURAXIAL ANESTHESIA OR UNDERGOING
SPINAL PUNCTURE. THE RISK OF THESE EVENTS MAY BE INCREASED BY THE USE
OF IN-DWELLING EPIDURAL CATHETERS OR THE CONCOMITANT USE OF
MEDICAL PRODUCTS AFFECTING HEMOSTASIS. THESE HEMATOMAS MAY
RESULT IN LONG-TERM OR PERMANENT PARALYSIS. CONSIDER THESE RISKS
WHEN SCHEDULING PATIENTS FOR SPINAL PROCEDURES.

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Select Important Safety Information
14
¡Active pathological bleeding
¡Severe hypersensitivity reaction to Bevyxxa
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
Risk of Bleeding
¡Bevyxxaincreases the risk of bleeding and can cause serious and potentially fatal bleeding.
¡Concomitant use of drugs affecting hemostasis increases the risk of bleeding. These include aspirin and other
antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, selective serotonin reuptake inhibitors,
serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs)
See additional Important Safety Information in full Prescribing Information available at this program

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Select Important Safety Information
15
Risk of Bleeding, cont’d
¡Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room
¡Promptly evaluate any signs or symptoms of blood loss and consider the need for blood replacement
¡Discontinue Bevyxxain patients with active pathological bleeding
¡There is no established way to reverse the anticoagulant effect of Bevyxxa, which can be expected to persist for at
least 72hours after the last dose.
WARNINGS AND PRECAUTIONS
See additional Important Safety Information in full Prescribing Information available at this program

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Targeted Mechanism of Action
16
LMWH=low molecular weight heparin; UFH=unfractionated heparin.
1. Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc. 2. Lassen MR, LauxV. VascHealth Risk Manag. 2008(6);4:1373-1386.
Factor
Xa
Extrinsic PathwayIntrinsic Pathway
ThrombinProthrombin
Betrixaban directly inhibits activation of Factor Xa, inhibiting downstream activation of thrombin1,2
Betrixaban
LMWH/UFH
Antithrombin-
dependent
indirect inhibition
Fibrin ClotFibrinogen
XII
XI
IX
VIII
VII

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HALF-LIFE METABOLISM
ABSORPTION
Pharmacokinetics of Bevyxxa
17
Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc.
§Effective half-life of 19-27 hours
§Primarily metabolized by
CYP-independent hydrolysis
§Mean peak concentrations in 3-4 hours
with loading dose
§Food reduces Cmaxand AUC
EXCRETION
§Mostly excreted in feces as unchanged
compound
§11% recovered in urine

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APEX Trial
18
Cohen AT et al. Am Heart J. 2014;167(3):335-341.
OBJECTIVE
Demonstrate the safety and efficacy of in-hospital and extended-duration
(35-42 days) anticoagulation with Bevyxxacompared to standard of care
anticoagulation with enoxaparin (6-14 days) followed by placebo for
prevention of VTE in acutely ill medical patients
PATIENTS OBJECTIVE ENDPOINTS STUDY DESIGN

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Additional Risk Factors:
•Previous VTE or superficial vein thrombosis
•History of NYHA Class III or IV HF
•Concomitant acute infection
•Obesity (BMI >35)
•History of cancer
•Inherited or acquired thrombophilia
•Current use of erythropoiesis stimulating agent
•Hormone Therapy
OBJECTIVE OBJECTIVE ENDPOINTS PATIENTS
INCLUDED STUDY DESIGN
APEX Trial Inclusion Criteria
19
Cohen AT et al. Am Heart J. 2014;167(3):335-341.
HOSPITALIZED FORACUTE MEDICAL ILLNESS
EXPECTED MODERATE / SEVERE IMMOBILITY
Heart Failure, Respiratory Failure, Infectious Disease, Rheumatic Disease, or Ischemic Stroke
≥75 years60to 74 years40 to 59 years
Eligible
2 Additional Risk Factors
OR
D-Dimer >2x ULN
History of VTE ORHistory of Cancer
+
1 Additional Risk Factor OR D-dimer > 2x ULN
AGE AND ADDITIONAL VTE RISK FACTORS

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OBJECTIVE OBJECTIVE ENDPOINTS PATIENTS
EXCLUDED1,2 STUDY DESIGN
APEX Trial Exclusion Criteria
20
1. Cohen AT et al. N EnglJ Med. 2016;375(6):534-544. 2. Cohen AT et al. Am Heart J. 2014;167(3):335-341.
HOSPITALIZED FORACUTE MEDICAL ILLNESSEnd-stage renal disease with CrCl<15 mL/min, or requiring dialysis
APEX isthe first extended thromboprophylaxistrial to enroll patients with CrCl<30 mL/min
Anticipated need for prolonged anticoagulation
Current intake of dual antiplatelet therapy
Anticipated major surgery
History of clinically significant bleeding within 6 months prior to enrollment
History of intracranial bleeding, head trauma, or known intracranial lesions
History of significant gastrointestinal, pulmonary or genitourinary bleeding, ongoing chronic peptic ulcer
disease or ongoing or acute gastritis within 2 years prior to enrollment
Hemoglobin <9.5 g/dLor unstable/declining hemoglobin

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OBJECTIVE
APEX Trial
21
CrCl=creatinine clearance;P-gp=P-glycoprotein; SC=subcutaneous.
1. Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc. 2. Cohen AT et al. Am Heart J. 2014;167(3):335-341.
3. Cohen AT et al. N EnglJ Med. 2016;375(6):534-544.
LOADING DOSE
160 mg
DOUBLE
-BLIND
DOUBLE
-DUMMYR
DAY 1
ENROLLMENT
(N=7513)
Bevyxxa80 mg oral once daily
Primary
Endpoint
Assessment
DAYS 32-47
Follow-up
Safety
Visit
DAYS 65-77
EXTENDED PROPHYLAXIS STANDARD
PROPHYLAXIS EVALUATION
Dosing adjustments:
§In severe renal insufficiency (CrCl 15 to <30 mL/min):
Bevyxxa40 mg (80 mg loading dose); enoxaparin 20 mg SC daily.
§In Bevyxxapatients taking concomitant strong P-gpinhibitors:Bevyxxa40 mg (80 mg loading dose).
6-14 DAYS 35-42 DAYS
OBJECTIVE PATIENTS ENDPOINTS STUDY DESIGN1-3
Enoxaparin
40 mg SC dailyPlacebo

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OBJECTIVE
APEX Trial
22
DVT=deep vein thrombosis;PE=pulmonary embolism.
Cohen AT et al. Am Heart J. 2014;167(3):335-341.
PRIMARY EFFICACY ENDPOINT
Composite of VTE-related death, non-fatal PE, asymptomatic proximal DVT, or
symptomatic DVT
SECONDARY EFFICACY ENDPOINT
Composite of symptomatic VTE (VTE-related death, non-fatal PE or symptomatic
DVT) through day 42
PRIMARY SAFETY ENDPOINT
Occurrence of major bleeding through 7 days after discontinuation of all study
medication
OBJECTIVE PATIENTS ENDPOINTS STUDY DESIGN

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APEX Patient Characteristics at Baseline
BACKGROUND DEMOGRAPHICS AND MEDICATIONS
23
Cohen AT et al. N EnglJ Med. 2016;375(6):534-544.
CharacteristicBevyxxa(N=3759)Enoxaparin (N=3754)
Age,years 76.6 ±8.5 76.2 ±8.3
Male,n (%) 1705 (45)1720 (45.8)
Mean weight,kg 79.8 80.7
BMI, kg/m2 29.2 ±6.6 29.5±6.7
Medianlength of hospitalization, days (IQR) 10 (7-14) 10 (8-14)
Creatinine clearance, n (%)
15-30 mL/min 174 (4.6)150 (4.0)
30 to <60 mL/min1602 (42.6) 1531 (40.8)
60 to <90 mL/min1299 (34.6)1346 (35.9)
>90 mL/min 672 (17.9)716 (19.1)
Race or ethnic group , n (%)
White 3503 (93.2)3518 (93.7)
Non-white/other256 (6.8)236 (6.3)
Concomitant P-gpinhibitor, n (%)677 (18.0)649 (17.3)
Previous thromboprophylaxis ≤96hours, n (%)1928 (51.3)1879 (50.1)
Over 80% of patients had
mild, moderate, or severe
renal impairment

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APEX Patient Characteristics at Baseline
24
1. Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc. 2. Data on file. Portola Pharmaceuticals. 3. Cohen AT et al. N EnglJ Med. 2016;375(6):534-544.
PRIMARY ACUTE MEDICAL ILLNESS1
Heart Failure
45%
Infection
29%
Respiratory
Failure
12%
Ischemic
Stroke
11%
Rheumatic
Disorders
3%
ADDITIONAL VTE RISK FACTORS1-3
% of Patients
Age >75 years 68%
D-dimer >2x ULN 62%
History of NYHAClass III or IV heart
failure
23%
Obesity (BMI> 35) 19%
Severe varicosities19%
Concurrent acute infection16%
History of cancer12%
Previous VTE 8%
Hormonereplacement therapy1.0%
Inheritedor acquired thrombophilia0.1%

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Over 3/4 of Patients Received Bevyxxa80 mg Once Daily
25
Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc..
DOSE RECEIVED
(mITTPOPULATION)
Bevyxxa 80 mg…
Bevyxxa 40 mg …
Severe Renal Impairment
(CrCl15-30 mL/min)
n=174
Concomitant P-gpInhibitors
n=669
Modified intent-to-treat population includes all patients who have taken at least 1 dose of study medication and who had follow-up
assessment data on 1 or more primary or secondary efficacy outcome components.

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6.0%
0.57%
4.4%
0.67%
0.0%
2.0%
4.0%
6.0%
8.0%
EnoxaparinBevyxxa
Primary Efficacy and Safety Endpoint
26
Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc.
PRIMARY SAFETY OUTCOME
MAJOR BLEEDING
21/371625/3716223/3720165/3721
RELATIVE RISK= 1.19
(95% CI 0.67-2.12)
P=0.554
PRIMARY EFFICACY OUTCOME
TOTAL VTE or VTE-RELATED DEATH
25 %RELATIVE RISK
REDUCTION
(95% CI 0.09-0.39)
NNT=63
mITTPOPULATION SAFETY POPULATION
EVENT RATE
(%)
80 MG& 40 MGDOSES

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Primary Efficacy and Safety Endpoint
27
Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc.
PRIMARY SAFETY OUTCOME
MAJOR BLEEDING
6.2%
0.53%
4.2%
0.50%
0.0%
2.0%
4.0%
6.0%
8.0% Enoxaparin
Bevyxxa
16/299115/2986180/2926120/2878
RELATIVE RISK=0.94
(95% CI 0.47-1.90)
PRIMARY EFFICACY OUTCOME
TOTAL VTE or VTE-RELATED DEATH
32 %RELATIVE RISK
REDUCTION
(95% CI 0.14-0.45)
NNT=50
mITTPOPULATION SAFETY POPULATION
EVENT RATE
(%)
80 MGDOSE

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Primary Efficacy Endpoint
28
Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc..
TOTAL VTE or VTE-RELATED DEATH
6.7%
5.1%
6.9%
4.9%
0%
2%
4%
6%
8% Enoxaparin
Bevyxxa 40 mg
RELATIVE RISK=1.0
(95% CI 0.45-2.23)
10
149
12
174
33
645
33
669
RELATIVE RISK=1.0
(95% CI 0.63-1.60)
SEVERE RENAL IMPAIRMENT
(CrCl15-30 mL/min)
mITTPOPULATION
CONCOMITANT P-GPINHIBITOR USE
EVENT RATE
(%)
40 MGDOSE

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1.4%
0.80%
0.0%
1.0%
2.0%
3.0%
Secondary Efficacy Endpoint
29
Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc.
SYMPTOMATIC VTE EVENT
SYMPTOMATIC EVENTS INCLUDE SYMPTOMATIC DVT, NON-FATAL PE OR VTE-RELATED DEATH
¢Enoxaparin
¢Bevyxxa80 mg
41
2926
22
2878
45%
(95% CI 0.08-0.67)
RELATIVE RISK
REDUCTION
mITTPOPULATION
EVENT RATE
(%)
80 MGDOSE

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Time to Symptomatic VTE Event Through End of Trial (Post-Hoc)
30
Data on file. Portola Pharmaceuticals
TIME TO SYMPTOMATIC VTE EVENT
mITTPOPULATION80 MGDOSE
PROBABILITY OF SYMPTOMATIC EVENT (%)
Time (Days)
¢Enoxaparin
¢Bevyxxa
1.84%
0.86%
051015202530354045505560657075
0
0.5
1.0
1.5
2.0
2.5
3.0
THROUGH END OF TRIAL
HR=0.48
(95% CI: 0.29-0.78)
Enoxaparin
In-Hospital & Extended VTE BevyxxaProphylaxis
No Therapy
Placebo
P=0.0029

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Primary Safety Endpoint
31
Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc.
SAFETY POPULATION80 MG& 40 MGDOSES
0.57% 0.67%
0.0%
2.0%
4.0%
6.0%
8.0%
Enoxaparin (n=3716)
Bevyxxa (n=3716)
21/371625/3716
PRIMARY SAFETY OUTCOME
MAJOR BLEEDING
RELATIVE RISK=1.19
(95% CI 0.67-2.12)
P=0.554
EVENT RATE
(%)
TYPES OF MAJOR BLEEDING
Enoxaparin
(N=3716)
n (%)
Betrixaban
(N=3716)
n (%)
Gastrointestinal9 (0.24)19(0.51)
Intracranial
Hemorrhage7 (0.19)2 (0.05)
Intraocular1 (0.03)0 (0)
Fatal Bleeding1 (0.03)1 (0.03)

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1.02%
2.45%
0.0%
2.0%
4.0%
6.0%
8.0%
Enoxaparin (n=3716)
Bevyxxa (n=3716)
32
Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc.
Most CRNM bleeding events were mild to moderate in severity and did not require or prolong hospitalization.
CLINICALLY RELEVANT NONMAJOR (CRNM) BLEEDING
CRNM is defined as overt bleeding not meeting criteria for major bleeding but associated with medical intervention, unscheduled contact with a physician,
cessation of study treatment, or with discomfort for the patient.
38 /3716
Secondary Safety Endpoint: CRNM Bleeding
SAFETY POPULATION80 MG& 40 MGDOSES
91 / 3716
RELATIVE RISK=2.39
(95% CI 1.64-3.49)
P<0.001
EVENT RATE
(%)

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Select Important Safety Information
33
Spinal/Epidural Anesthesia or Puncture
¡When neuraxialanesthesia (spinal/epidural anesthesia) or spinal/epidural puncture is employed, patients treated
with antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural
or spinal hematoma which can result in long-term or permanent paralysis.
¡An epidural catheter should not be removed earlier than 72 hours after the last administration of Bevyxxa. The
next BEVYXXA dose is not to be administered earlier than 5 hours after the removal of the catheter. If traumatic
puncture occurs, delay the administration of Bevyxxafor 72 hours.
¡Monitor patients frequently for signs and symptoms of neurological impairment (e.g., numbness or weakness of
the legs, bowel, or bladder dysfunction). If neurological compromise is noted, urgent diagnosis and treatment is
necessary.
WARNINGS AND PRECAUTIONS
See additional Important Safety Information in full Prescribing Information available at this program

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Select Important Safety Information
34
Use in Patients with Severe Renal Impairment
¡Patients with severe renal impairment (CrCl≥ 15 to < 30 mL/min computed by Cockcroft-Gault) taking Bevyxxa
may have an increased risk of bleeding events
¡Reduce dose of Bevyxxa, monitor patients closely, and promptly evaluate any signs or symptoms of blood loss in
these patients.
Use in Patients on Concomitant P-glycoprotein (P-gp) Inhibitors
¡Patients on concomitant P-gpinhibitors with Bevyxxamay have an increased risk of bleeding.
¡Reduce dose of Bevyxxa, monitor patients closely, and promptly evaluate any signs or symptoms of blood loss in
these patients.
¡Avoid use of Bevyxxain patients with severe renal impairment receiving concomitant P gpinhibitors.
WARNINGS AND PRECAUTIONS
See additional Important Safety Information in full Prescribing Information available at this program

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Select Important Safety Information
35
See additional Important Safety Information in full Prescribing Information available at this program
Hepatic Impairment
¡Bevyxxahas not been evaluated in patients with hepatic impairment, because these patients may have intrinsic
coagulation abnormalities
¡Bevyxxais not recommended in patients with hepatic impairment
USE IN SPECIFIC POPULATIONS

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BevyxxaDosing and Administration
36
Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc.
INITIAL DOSE
160 MG
DAILY DOSE
80 MG
DAY 1
Take at the same time each day
with food
RECOMMENDED DOSE
Recommended duration of
therapy is 35-42 days
DAY 2 DAYS 35 -42

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BevyxxaDosing Adjustments
37
Bevyxxa® [package insert]. South San Francisco, CA: Portola Pharmaceuticals, Inc.
INITIAL DOSE
80 MG
DAILY DOSE
40 MG
In patients receiving or starting P-gpinhibitors
eg, amiodarone, azithromycin, verapamil, ketoconazole,
or clarithromycin
REDUCED DOSE
In patients with severe renal impairment
CrCl15-<30mL/min
(calculated by Cockroft-Gault using actual body weight)

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BevyxxaSummary
38
In medically ill patients 60% of VTE risk accumulates from admission to 40 days
Bevyxxais the only oral anticoagulant indicated for prophylaxis of VTE
in adult patients hospitalized for an acute medical illness who are at risk for thromboembolic complications due
to moderate or severe restricted mobility and other VTE risk factors
Bevyxxa80 mg demonstrated a 32% relative risk reduction in VTE and VTE-related death
vs enoxaparin (NNT=50)
Use with caution in conditions where an increased risk of bleeding exists or is suspected
•Bevyxxaincreases the risk of bleeding and can cause serious and potentially fatal bleeding
•No significant increase in major bleeding vs enoxaparin
•Higher rates of CRNM bleeding vs enoxaparin. The majority of CRNM bleeds were mild to
moderate and did not require or prolong hospitalization

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THANK YOU!
39

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PATIENT CASES

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CASE 1:
76-YEAR-OLD MALE WITH HEART FAILURE*
41
*This is a hypothetical patient case.

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76-YEAR-OLD MALE WITH HEART FAILURE
42
INITIAL PRESENTATION
A 76-year-old man is admitted to the pulmonary step down unit with persistent cough, dyspnea, and bilateral
edema in the legs and is diagnosed with an acute heart failure exacerbation. He has difficulty moving about and
was brought in by his wife who says that because of his breathing difficulty he was unable to get out of bed for
the past 3 days, unless absolutely necessary.
MEDICAL HISTORY
§CHF (NYHA Class III), LVEF 29%
§Hypertension
§BPH
§GERD
CURRENT MEDICATIONS
§Lisinopril
§Furosemide
§Tamsulosin
§Esomeprazole
SOCIAL HISTORY
§Retired teacher who lives with his wife, who is his primary caretaker
ALLERGIES
§Penicillin
BPH=benign prostatic hyperplasia; CHF=congestive heart failure; GERD=gastroesophagealreflux disease; LVEF=left ventricular ejection fraction; NYHA=New York Heart Association.

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76-YEAR-OLD MALE WITH HEART FAILURE
43
PERTINENT PHYSICAL EXAM FINDINGS
§NECK: Jugular venous distension
§CHEST: Lungs are dull to percussion with bilateral
crackles; X-ray shows bilateral pleural effusions and
cardiomegaly
§HEART: S3 gallop noted, RRR, no fibrillation or flutter
§EXTREMITIES: Bilateral lower extremity edema, minimal
clubbing
§ABDOMEN: Liver edge palpable and tender, consistent
with hepatomegaly
BMP
VITALS
§HR: 112 bpm
§BP: 150/90 mm Hg
§R: 24
§Temp: 99°F
§O2saturation: 91%
CBC
§WBC: 6300 cells/mcL (normal differential)
§Hgb/Hct: 15.6 g/dL/44%
§Platelets: 230,000/m3
URINALYSIS
Normal
Na
133
Cl
93
BUN
33Glu
112K
3.9
HCO3
23
Cr
1.6
LFTs
Normal
HEIGHTWEIGHT BMI
5’7”72.5 kg25.1 kg/m2
BMI=body mass index; BMP=basic metabolic panel; BP=blood pressure; bpm=beats per minute; BUN=blood urea nitrogen; CBC=complete blood count; Hgb=hemoglobin; Hct=hematocrit;
HR=heart rate; INR=international normalized ratio; LFT=liver function test; PT=prothrombin time; RR=respiratory rate; RR=regular rate and rhythm; Temp=temperature;
WBC=white blood cells.
OTHER
Normal PT and
INR
CrCl
40 mL/min
(Cockroft-Gault using
actual body weight)

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76-YEAR-OLD MALE WITH HEART FAILURE
44
ASSESSMENT OF VTE RISK
R
§Limited mobility (bedridden for 3 days and anticipated length of
hospitalization at least 4 days)
§Hospitalization for heart failure (candidate for admission)
§76 years old
PADUA PREDICTION SCORE
Risk FactorPoints
Heart failure 1
Elderly (≥70 years)1
Immobilization for ≥3days3
Total Score
SCORES≥4 ASSOCIATED WITH HIGHVTE RISK
5
IMPROVE VTE RISK ASSESSMENT
Risk FactorPoints
Age >60years 1
Immobilization for at least 7 days
(prior to and during hospital admission)
1
Total Score
SCORES≥2 ASSOCIATED WITH HIGHVTE RISK
2
APEX CRITERIA MET
§≥40 years
§Hospitalization for acute medical illness (Heart
failure)
§Moderate to severe immobilization (at least 24
hours) and expected hospitalization at least 3 days

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76-YEAR-OLD MALE WITH HEART FAILURE
45
PATIENT MANAGEMENT
§Patient is admitted to the pulmonary step down unit for decompensated CHF and later transferred to
the general medical floor and is hospitalized for a total of 7 days
§During his stay, he receives supplemental oxygen to manage hypoxemia and IV diuretics
for volume overload
§He is a candidate for extended VTE prophylaxis and receives a loading dose of 160 mg betrixaban on
his first day. He receives daily doses of 80 mg while hospitalized and is discharged with a
35-day supply
IV=intravenous.

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CASE 2:
68-YEAR-OLD FEMALE WITH PNEUMONIA*
46
*This is a hypothetical patient case.

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68-YEAR-OLD FEMALE WITH PNEUMONIA
47
INITIAL PRESENTATION
A 68-year-old woman is hospitalized due to frequent productive coughing, worsening exertional dyspnea, purulent
sputum production, and fever lasting 3 days. Symptoms have not resolved after self-medication with OTC products and
she has been unable to get out of bed for 2 days. She is brought in by her daughter and admitted for management of
community-acquired pneumonia.
MEDICAL HISTORY
§Hyperlipidemia
§Hypertension
§COPD
§Type 2 diabetes
§Osteoarthritis in both knees
§Breast cancer 4 years s/p partial mastectomy
CURRENT MEDICATIONS
§Atorvastatin
§Verapamil
§Budesonide/formoterol
§Metformin
§Naproxen
SOCIAL HISTORY
§Part-time paralegal who lives alone. Her daughter lives 45 minutes away and will occasionally check in
on her
§Largely sedentary lifestyle; obese
§Former smoker (2 packs/day); 40 pack-year history
ALLERGIES
§NKDA
§Shellfish
COPD=chronic obstructive pulmonary disease; NKDA=no known drug allergies; OTC=over the counter; s/p=status post.

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68-YEAR-OLD FEMALE WITH PNEUMONIA
PERTINENT PHYSICAL EXAM FINDINGS
§CHEST: wheezing, diminished breath sounds, scattered
crackles; chest X-ray shows left lower lobe infiltrate
§HEART: normal heart sounds
BMP
VITALS
§HR: 92 bpm
§BP: 132/90 mm Hg
§R: 28
§Temp: 103°F
§O2saturation: 89%
CBC
§WBC: 17,000 cells/mcL
(neutrophils 80%, bands 10%, lymphocytes 10%)
§Hgb/Hct: 14 g/dL/43%
§Platelets: 110,000/m3
URINALYSIS
§Normal
Na
150
Cl
115
BUN
35Glu
112K
4.5
HCO3
24
Cr
1.1
LFTs
§Normal
HEIGHTWEIGHT BMI
5’5”84.3 kg30.9 kg/m2
CULTURES
§Sputum culture reveals Streptococcus pneumoniae
BMI=body mass index; BMP=basic metabolic panel; BP=blood pressure; bmp=beats per minute; BUN=blood urea nitrogen; CBC=complete blood count; Hgb=hemoglobin;
Hct=hematocrit; HR=heart rate; LFT=liver function test; RR=respiratory rate; Temp=temperature; WBC=white blood cells.
CrCl
65 mL/min
(Cockroft-Gault using
actual body weight)

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68-YEAR-OLD FEMALE WITH PNEUMONIA
49
PADUA PREDICTION SCORE
Risk FactorPoints
Respiratoryfailure 1
Obesity (BMI ≥30) 1
Acute infection1
Immobilization for ≥3days3
Total Score
SCORES≥4 ASSOCIATED WITH HIGHVTE RISK
6
IMPROVE VTE RISK ASSESSMENT
Risk FactorPoints
Age >60years 1
Immobilization for at least 7 days
(prior to and during hospital admission)
1
Total Score
SCORES≥2 ASSOCIATED WITH HIGHVTE RISK
2
ASSESSMENT OF VTE RISK
R
§Limited mobility (bedridden for 2 days and anticipated
hospitalization at least 5 days for antibiotic course)
§Hospitalization for acute infection
§68 years old
§COPD
APEX CRITERIA MET
§≥40 years
§Hospitalization for acute medical illness (Pneumonia)
§Moderate to severe immobilization (at least 24
hours) and expected hospitalization at least 3 days

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68-YEAR-OLD FEMALE WITH PNEUMONIA
50
PATIENT MANAGEMENT
§Patient is admitted to the general medical unit for management of community-acquired pneumonia
§She is given IV fluids and started on a 5-day course of IV and oral antibiotics. During her stay she also
receives supplemental oxygen to help with breathing
§She is a candidate for extended-duration VTE prophylaxis and should receive reduced-dose
betrixaban due to her concomitant verapamil use. She is given a loading dose of betrixaban 80 mg
on day 1 and daily doses of betrixaban 40 mg while hospitalized
§By day 7, the patient is afebrile and her cultures have come back clear. She is discharged to a
long-term care facility for better management of her multiple comorbidities
§She receives a prescription for 35 days of betrixaban 40 mg once-daily
IV=intravenous.