Stopping the Shot for Prevention of Clots: Oral · 2018. 9. 15. · Stopping the Shot for...

Stopping the Shot for Prevention of Clots: Oral

Options for Cancer-Associated Venous

ThromboembolismSamarth Shah, PharmD, BCPS

Assistant Professor of Clinical Sciences, Roosevelt University College of Pharmacy

Clinical Specialist, Internal Medicine, Rush University Medical Center

Yana Labinov, PharmD, BCPS



Yash Desai, PharmD Candidate

Roosevelt University College of Pharmacy

The speakers declare no conflicts of interest, real or apparent, and no

financial interests in any company, product, or service mentioned in this

program, including grants, employment, gifts, stock holdings and honoraria.

Disclosures and Conflict of Interest

At the conclusion of the program, the pharmacists will be able to:

1. Describe the mechanism of action, indications, and dose adjustments needed

for the direct oral anticoagulants (DOACs).

2. Describe the utilization of DOACs for venous thromboembolism (VTE), atrial

fibrillation (AF), and malignancy related thromboembolism.

3. Review evidence-based recommendation for malignancy related

thromboembolism and determine if DOACs may play a role in this patient

population.

Pharmacist Objectives

At the conclusion of this program, the pharmacy technician will be able to:

1. Identify the trade name of the DOACs.

2. Describe the role of DOACs in the prevention of thromboembolism and stroke

prevention.

3. Identify patients who may benefit from DOAC therapy compared to traditional

vitamin K antagonist (VKA) therapy, such as warfarin.

Technician Objectives

A. Vitamin K antagonist

B. Direct Thrombin Inhibitor

C. Factor Xa Inhibitor

D. Tissue plasminogen activator

Question 1: Apixaban is a(n):

A. Apixaban

B. Rivaroxaban

C. Dabigatran

D. Edoxaban

E. Betrixaban

Question 2: Which of the following DOACs

require parenteral anticoagulation for initial

treatment of VTE?

A. DOACs

B. Vitamin K antagonists

C. Low molecular weight heparins (LMWHs)

Question 3: Which of the following classes of

medications is first line for prevention of

cancer-associated VTE?

Coagulation Cascade and Target

Intrinsic Pathway

Extrinsic Pathway

Direct FXa inhibitors(rivaroxaban, apixaban, edoxaban, betrixaban)

Direct thrombin inhibitors(dabigatran)

FDA IndicationDabigatran

(Pradaxa®)

Rivaroxaban

(Xarelto®)

Apixaban

(Eliquis®)

Edoxaban

(Savaysa®)

Betrixaban(Bevyxxa®)

VTE Treatment ✔️ ✔️ ✔️ ✔️

VTE Prophylaxis ✔️ ✔️

Stroke Prevention in

Atrial Fibrillation✔️* ✔️ ✔️ ✔️*

Postoperative

Prophylaxis

(THA/TKA)

Hip only ✔️ ✔️

Indications

*After 5 to 10 days of initial therapy with a parenteral anticoagulantLexicomp Online® , Pediatric & Neonatal Lexi-Drugs® , Hudson, Ohio: Lexi-Comp, Inc.; May 18, 2018

Comparison of DOACsDabigatran

(Pradaxa®)

Rivaroxaban

(Xarelto®)

Apixaban

(Eliquis®)

Edoxaban

(Savaysa®)


Target IIa Xa Xa Xa Xa

Tmax (hr) 1-3 2-4 1-3 1-2 3-4

Bioavailability (%) 3-766 (without food)100 (with food)

50 62 34

CYP MetabolismNo

Prodrug to active form via esterases

YesCYP3A4, CYP3A5,

CYP2J2

YesCYP3A4, CYP3A5

YesCYP3A4 (4%)

NoHydrolysis in the

gut

Renal elimination(%)

80% 35% 27% 50% 11%

PGP substrate Yes Yes Yes Yes Yes

Half-life (hr) 12-17 5-13 8-15 10-14 19-27

Lexicomp Online® , Pediatric & Neonatal Lexi-Drugs® , Hudson, Ohio: Lexi-Comp, Inc.; May 18, 2018

Dabigatran Rivaroxaban

Apixaban Edoxaban

EP Europace, 2015; 17(10):1467–1507

Estimated drug half lives and effect on AUC NOAC plasma

concentrations in different stages of CKD compared to healthy

controls

Dabigatran

(Pradaxa®)

Rivaroxaban

(Xarelto®)

Apixaban

(Eliquis®)

Edoxaban

(Savaysa®)

CrCl > 80 mL/min 12-17 h5-9 (young)

11- 13 (elderly)8-15 h 10-14 h

CrCl 50 – 80 mL/minCKD Stages I -II

~ 17(+50%)

~ 8.7 h(+44%)

~14.6 h(+16%)

~8.6 h(+32%)

CrCl 30 – 50 mL/minCKD Stage III

~19 h (+320%)

~9 h(+52%)

~17.6 h(+29%)

~9.4 h(+74%)

CrCl 15 – 30 mL/minCKD Stage IV

~28 h(+530%)

~9.5(+64%)

~17.3 h(+44%)

~16.9 h(+72%)

CrCl < 15 mL/minCKD Stage V, off-HD

No data-

(+70%)-

(+36%)(+93%)

EP Europace, 2015; 17(10):1467–1507

Comparison of DOACs

Dabigatran

(Pradaxa®)

Rivaroxaban

(Xarelto®)

Apixaban

(Eliquis®)

Edoxaban

(Savaysa®)


Antidote available Yes Yes Yes No No

DialyzableYes No No No No

Drug interactions P-gp* P-gp*, CYP3A4 P-gp*, CYP3A4 P-gp*, CYP3A4 P-gp*

Pregnancy Category C C B C Not assigned

Transition from warfarin

1st dose when INR < 2



1st dose when INR ≤ 2.5

1st dose when INR ≤ 2.5

Notable ADRsDyspepsia (5-

10%; liver injury

- -Rash, abnormal

LFTs-

Contraindication are bleeding and hypersensitivity for the above DOACs

*P-gp: P-glycoproteinLexicomp Online® , Pediatric & Neonatal Lexi-Drugs® , Hudson, Ohio: Lexi-Comp, Inc.; May 18, 2018

Administration Considerations

Dabigatran

Capsules cannot be crushed, broken, or chewed

Expires 4 months after the bottle is opened

Rivaroxaban

Tablets (all strengths) may be crushed and mixed with applesauce

15 and 20 mg tablets need to be taken WITH FOOD

For nasogastric/gastric feeding tube administration, the tablets (all strengths) may be crushed and mixed in 50 mL of water

Apixaban

May crush 5 mg or 2.5 mg tablets and suspend in 60 mL of water, D5W, or apple juice or mix with applesauce

For nasogastric tube administration, crushed tablets may be suspended in 60 mL of water or D5W

Edoxaban

Tablets may be crushed and mixed with applesauce or 60 to 90 mL water

For nasogastric tube administration, mix crushed tablets with 60 to 90 mL water

Betrixaban

Must be taken with food

No information on crushing available

Lexicomp Online® , Pediatric & Neonatal Lexi-Drugs® , Hudson, Ohio: Lexi-Comp, Inc.; May 18, 2018

AF Clinical Trial Overview

RE-LY ROCKET- AF ARISTOTLE ENGAGE-TIMI 48

Drug Regimen and Dose

Adjustments (if applicable)

Dabigatran 150 mg or 110 mg BID

Rivaroxaban 20 mg qdaily

Rivaroxaban 15 mg qdailyCrCl 30-49 mL/min

Apixaban 5 mgBIDOR

Apixaban 2.5 mg BID if 2 of:

Age > 80 yrs, weight < 60 kg, Scr > 1.5mg/dL

Edoxaban 30 or 60 mg

daily

Both doses halved if:

weight < 60 kg, CrCl 30- 50

mL/min, use of strong Pgp

inhibitor (verapamil,

quinidine, dronedarone)

Study DesignOpen label RCT

(N = 18,113)

Double-blindRCT

(N = 14,264)

Double-blindRCT

(N = 18,201)

Double-blindRCT

(N = 21,105)

Mean age (years) 71.5 73 70 72

Mean CHADS2 2.1 3.5 2.1 2.8

Time in therapeutic range (%) 64 58 62 65

Previous stroke/TIA (%) 20 55 20 28.5

Warfarin naïve (%) 50 37.7 43 411.Connolly SJ et al. N Engl J Med. 2009;361(12):1139-1151; 2. Patel MR et al. N Engl J Med 2011; 365:883-891; 3. Granger CB et al. N Engl J Med. 2011;365(11):981-992; 4. Giugliano RP et al. N Engl J Med. 2013; 369:2093-2104.

DOACs vs Warfarin in AF: Stroke or Systemic Embolism

Ruff C et.al. Lancet 2014;383:955-962

DOACs vs Warfarin in AF: Major Bleeding


DOACs vs Warfarin in AF: Secondary Efficacy and Safety Outcomes


VTE Clinical Trial Overview

RECOVER RECOVER II EINSTEIN DVT EINSTEIN PE AMPLIFY HOKUSAI

Drug Regimen and

Dose

Parenteral ≥ 5 days

+ dabigatran 150 mg BID

Parenteral ≥ 5 days

+ dabigatran 150 mg BID

Rivaroxaban 15

mg x 21 days, then

20 mg daily

Rivaroxaban 15

mg x 21 days, then

20 mg daily

Apixaban 10 mg BID x 7 days, then

5 mg BID

Parenteral ≥ 5

days

+ edoxaban 30 mg

or 60 mg daily

Study Design

Double-blind,RCT, NF

(N= 2564)


(N= 2589)

Open-label,RCT,NF

(N= 3449)

Open-label,RCT, NF

(N= 4833)


(N= 5400)


(N= 8292)

Mean age (years) 55 56 58 57 56

Active Cancer(%) 5 4 6 5 3 9

Time in therapeuticrange (%)

60 57 58 63 61 63

Gómez-Outes A, et al, Direct oral anticoagulants in the treatment of acute venous thromboembolism: A systematic review and meta-analysis, Thromb Res (2014)

DOACs in VTE: Recurrent VTE

Kkkos SK, et al., Efficacy and Safety of the New Oral Anticoagulants Dabigatran, Rivaroxaban, Apixaban, and Edoxaban n the Treatment and Secondary Prevention of Venous Thromboembolism: A Systematic Review and Meta-analysis of Phase III Trials, European Journal ofVascular and Endovascular Surgery (2014), http://dx.doi.org/10.1016/j.ejvs.2014.05.001

Recurrent Symptomatic VTE

Deep Vein Thrombosis

Dri

ven

by

DOACs in VTE: Major and CRNM Bleeding

Kkkos SK, et al., Efficacy and Safety of the New Oral Anticoagulants Dabigatran, Rivaroxaban, Apixaban, and Edoxaban n the Treatment and Secondary Prevention of Venous Thromboembolism: A Systematic Review and Meta-analysis of Phase III Trials, European Journal ofVascular and Endovascular Surgery (2014), http://dx.doi.org/10.1016/j.ejvs.2014.05.001

Major Bleeding

CRNM Bleeding

DOACs Dosing in VTE

Dabigatran

(Pradaxa®)

Rivaroxaban

(Xarelto®)

Apixaban

(Eliquis®)

Edoxaban

(Savaysa®)

CrCl > 30 mL/min: 150 mg PO BID after 5-10 days of parenteral anticoagulation

CrCl < 50 mL/min with use if a P-gp inhibotrs: Avoid use

CrCl < 30 mL/min or on dialysis: Avoid use

CrCl ≥ 30 mL/min: 15 mg PO BID x 21 days, then 20mg po QD;

CrCl < 30 mL/min: Avoid use

The Beers Criteria recommends reducing the dose in adults ≥65 years with a CrCl between 30 and 50 mL/minute (specific dosage adjustment not provided)

10 mg PO BID for 7 days, then 5 mg po BID

Reduction in the risk of recurrent DVT and PE following initial therapy of at least 6 months: 2.5 mg po BID

No dosage adjustment is recommended by the manufacturer for any degree of renal impairment. However, patients with a serum creatinine >2.5 mg/dL or CrCl <25 mL/minute (as determined by Cockcroft-Gault equation) were excluded from the clinical trials

60 mg PO daily after 5 -10 days of parenteral anticoagulation

CrCl 15 – 50 mL/min, < 60 kg, use of certain P-gpinhibitors: 30 mg PO daily

CrCl: Creatinine ClearanceLexicomp Online® , Pediatric & Neonatal Lexi-Drugs® , Hudson, Ohio: Lexi-Comp, Inc.; May 18, 2018

Predictable pharmacokinetics and pharmacodynamics

Fewer drug–drug and food interactions

No dietary restriction

Rapid onset and offset

Short half-life

No need for laboratory monitoring

DOAC Advantages

Therapeutics and Clinical Risk Management 2015; 11: 967–977.

No established method of monitoring for efficacy

Standardized monitoring schedule/guidelines do not exist for patients with hepatic or renal dysfunction

Necessitates strict patient compliance

Not FDA approved for patients with valvular-AF

Cost

DOAC Disadvantages

Therapeutics and Clinical Risk Management 2015; 11: 967–977.

DOACs recommended over VKA CHEST for long-term anticoagulant treatment (3 months) of non-cancer VTE patients

For those who are intolerant or cannot be treated with the DOACs, the guidelines recommend VKAs over LMWHs

For VTE patients with cancer, however, LMWHs remain the recommended choice for long-term antithrombotic therapy

Current Guidelines Recommendation

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016;149:315-352

http://www.sciencedirect.com/science/article/pii/S0012369215003359

Malignancy Associated Venous

Thrombosis

Estimated that 20-30% of all first venous thromboembolic events are cancer

associated

Patients with cancer have a several-fold increase of VTE compared with the

general population or patients without cancer

Absolute risk of VTE in cancer patients varies widely (1-8%) and is highly

dependent on

Patient population

Duration of follow-up

Type of cancer

Cancer patients at 2-3 fold increased risk of recurrent venous thrombosis

compared to non-cancer patients

Introduction

Blood. 2013; 122(10):1712-1723

Different types and stages of cancer should be taken into account when

determining the risk of VTE

High correlation between aggressiveness of cancer and thrombogenic

potential

Risk Factors for VTE in Cancer Patients

Blood. 2013; 122(10):1712-1723

Highest Risk High Risk Low Risk

Pancreas Lymphomas Breast

Brain Myeloma

Prostate Lung Kidney

OvarianStomach

Bone

Incidence rates of venous thrombosis

per type of Cancer

Blood. 2013; 122(10):1712-1723

Thrombotic events are second leading cause of death in cancer patients

Cancer patients who develop VTE have lower survival rate than cancer

patients without VTE

Patients with cancer-associated VTE have higher rates of bleeding

complications during anticoagulant treatment and of recurrent VTE than

patients with VTE without cancer

The risk of bleeding is about two-fold higher

The Impact on Patients

Blood. 2013; 122(10):1712-1723

Key Point: VTE risk is increased in patients with cancer, but if treated with

anticoagulants, risk of bleeding increased as well!

Patients with multiple myeloma receiving antiangiogenesis agents with

chemotherapy and/or dexamethasone should receive prophylaxis with either

low-molecular weight heparin (LMWH) or low-dose aspirin to prevent venous

thromboembolism

LMWH is recommended for the initial 5-10 days of treatment of established

DVT/PE as well as long-term secondary prophylaxis for at least 6 months

Use of direct oral anticoagulants is not currently recommended for patients

with malignancy and VTE

Key Recommendations per American

Society of Clinical Oncology

J Clin. Onc. 2015. 33(6) (2015) 654-656

Key Point: LMWH recommended per guidelines for treatment of established

DVT/PE

N Engl J Med 2003;349:146-53.

CLOT (n = 672)

Design Randomized, open-label trial

Patients ▪ Patients with cancer who had acute, symptomatic

proximal deep-vein thrombosis, pulmonary embolism

▪ Patients excluded if low weight (< 40 kg), had active or

serious bleeding within previous 2 weeks, high risk of

bleeding, or platelet count < 75,000 mm3

Intervention Dalteparin vs. warfarin with a follow up duration of 6

months

Endpoints Primary outcome:

▪ Recurrent VTE rates

Secondary outcomes:

▪ Bleeding rates

▪ Mortality

CLOT Trial – Results

N Engl J Med 2003;349:146-53.

Rates of any bleed were 14% in the dalteparin group vs.

19% in the warfarin group (p = 0.09)

Significantly reduced rate of recurrent VTE in the dalteparin group vs.

warfarin group

No significant difference in bleeding rates

No significant difference in mortality

CLOT trial – Conclusions

N Engl J Med 2003;349:146-53.

Key Point: Trial that established LMWH as the mainstay in treatment of VTE

and recurrent VTE in patients with malignancy.

Meyer et. al (n = 146)

Design Randomized, open-label trial

Patients ▪ Patients with cancer who had acute, symptomatic

proximal deep-vein thrombosis, pulmonary embolism

▪ Less than 3 month life-expectancy, contraindication to

anticoagulant therapy, severe renal insufficiency

Intervention Enoxaparin vs. warfarin


▪ Composite of

treatment failure or

major bleeding

Secondary outcomes:

▪ 3 and 6 month mortality

▪ Major bleeding

▪ Recurrent VTE

Arch Intern Med 2002; 162:1729-1735

Arch Intern Med 2002; 162:1729-1735

Composite endpoint significant

Enoxaparin showed reduced

recurrent VTE rates compared to

warfarin (10.5% vs. 21.2%)

Similar rates of major bleeding

(7% vs 16%)

Similar rates of mortality

(11.3% vs. 22.7%)

Specific DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) have

emerged for the management of VTE

Oncology guidelines do NOT recommend DOACs, but due to the ease of use

and oral formulations, they may still be used

Guideline Recommendation vs. Real Life

Thrombosis Research. 2016; 145:51-53

Retrospective analysis of MarketScan® data-base

Contains more than 80 million patients in the United States

Contains employer-based healthcare claims

Among the 80 million patients, 1.7 were diagnosed with cancer and 6.2%

developed VTE

Newly diagnosed patients who developed VTE

59,911 (50.2) were prescribed anticoagulants

Evaluation of US Prescription Patterns


Warfarin

(n=26,456)

50%

LMWH

(n=21,164)

40%

DOACs

(n=5,291)

10%



Most recent data (2013-2014) saw an similar rates of utilization of

LMWH and an increase in DOAC utilization

Observed utilization of DOACs significantly increased in the most recent year

likely due to approval of new drugs

Seems as if current treatment practice favors DOACs over warfarin because

utilization of LMWH remained constant, while warfarin decreased

Role for simplified anticoagulation regimen that doesn’t require constant

monitoring and injections?



Hokusai VTE Cancer (n = 1046)

Design Open-label, non-inferiority trial

Patients ▪ Adult patients with cancer with confirmed VTE

▪ Patients excluded if life expectancy < 3 months,

contraindication to anticoagulation, or , CrCl < 30

mL/min

Intervention Edoxaban vs. dalteparin for 6-12 months


▪ Composite primary

outcome of

recurrent VTE and

major bleeding

Secondary outcomes:

▪ Recurrent venous

thromboembolism (VTE and PE)

▪ Major bleeding

▪ Death from any cause

N Engl J Med 2018; 349(7):615-624.

Hokusai VTE Cancer – Results

N Engl J Med 2018; 349(7):615-624.

Composite endpoint of venous thromboembolism or major bleeding showed

that statistical significance in edoxaban being non-inferior to dalteparin

Statistically significant difference in major bleeding, with the edoxban group

having increased rates of bleeding

These was seen more common in patients with GI cancers

No difference in death from any cause

Hokusai VTE Cancer – Conclusions

N Engl J Med 2018; 349(7):615-624.

Design of the trial was open-label

Anticoagulation duration was 12 months

Less than guideline based recommendation (continue indefinitely)

Could have lead to an increase in VTE occurrence in groups and a decrease in

bleeding in groups if continued long term rather than a finite amount of time

Hokusai VTE Cancer – Critiques

N Engl J Med 2018; 349(7):615-624.

Key Point: In patients with cancer-associated VTE, edoxaban

decreases the risk of recurrent VTE, but increases the bleeding risk

compared to dalteparin.

Lancet Haematol 2014;1: e37–46

EINSTEIN-PE and EINSTEIN-DVT Pooled Subgroup (n = 8281)

Design Subgroup analysis of patients with cancer from EINSTEIN-

PE and EINSTEIN-DVT

Patients ▪ Adult patients with confirmed VTE

Intervention Rivaroxaban vs. enoxaparin + warfarin (3, 6, 12 months)


▪ Symptomatic

recurrent venous

thromboembolism

Secondary outcomes:

▪ Clinically relevant bleeding

EINSTEIN DVT and EINSTEIN PE Subgroup

Analysis - Results


Similar efficacy in recurrent VTE between fixed-dose rivaroxaban vs.

enoxaparin + warfarin

Decreased bleeding rates in the rivaroxaban group compared to the

enoxaparin + warfarin group

Open-label study

Retrospective subgroup analysis

Warfarin part of comparator group

EINSTEIN DVT and EINSTEIN PE Subgroup

Analysis – Conclusions and Critiques


Key Point: In patients with cancer-associated VTE, rivaroxaban vs.

enoxaparin + warfarin is similar in decreasing rates of recurrent venous

thromboembolism, but rivaroxaban provides the benefit of a decreased

risk of bleeding, but further research needed.

Cancer patients in the AMPLIFY Trial (n = 159)

Design Subgroup analysis of patients with cancer from EINSTEIN-

PE and EINSTEIN-DVT

Patients ▪ Adult patients with confirmed VTE with active cancer

Intervention Apixaban vs. enoxaparin + warfarin (6 months)


▪ Symptomatic recurrent

venous

thromboembolism or

VTE related death

Secondary outcomes:

▪ Clinically relevant bleeding

J Thromb Haemost; 2015; 13:2187-2191

AMPLIFY Subgroup Analysis – Results

J Thromb Haemost; 2015; 13:2187-2191

Similar rates of recurrent VTE and bleeding between both groups

Recurrence rate in AMPLIFY was 6% which is lower than 15-20% reported in the

CLOT study

Warfarin part of comparator group

AMPLIFY Subgroup Analysis – Conclusion

and Critiques

J Thromb Haemost; 2015; 13:2187-2191

Key Point: In patients with cancer-associated VTE, apixaban may be a

convenient option, but additional studies needed.

Investigator initiated Phase IV, multicenter, randomized, open label,

superiority trial assessing safety of apixaban vs. dalteparin during a 6 month

treatment period of cancer associated VTE

Main objective is to compare safety of apixaban with dalteparin

Hypothesis that apixaban will have significantly lower rates of major bleeding

compared to dalteparin

Secondary objective are to assess efficacy

J Thromb Haemost; 2017; 117

CHEST; 2015; 147(2): 475-483

VTE Recurrence Meta-Analysis

CHEST; 2015; 147(2): 475-483

Bleeding Risk Meta-Analysis

DOACs seem to be at least safe and effective as conventional anticoagulant

treatment

The caveat is that all of these trials looked at vitamin K antagonist as the

comparator agent, and recommendations per guidelines are to use a LMWH

CHEST; 2015; 147(2): 475-483

Additional studies similar to the Housaki trial and the ADAM VTE trial may

shift practice patterns to prefer DOACs in patients due to feasibility and

possible better safety data

Recently the SELECT-D trial completed and results similar showing

rivaroxaban had a low recurrence of VTE, but had a higher risk of bleeding

Studies analyzing DOACs vs. LMWHs will need to be completed in order to

impact the guidelines

A Shift in Practice

Questions??

Which of the following DOACs are ONLY indicated for VTE prophylaxis?

a. Apixaban

b. Betrixaban

c. Edoxaban

d. Rivaroxaban

Post Test Question #1

Rivaroxaban and apixaban have indications for post-operative prophylaxis,

betrixaban is the only DOAC that has an indication for VTE prophylaxis

Post Test Question #1 Rationale

Based on the meta-analysis on DOACs patients with cancer who have VTE, which

of the following statements is MOST true?

a. DOACs should be avoided in patients due to inferior outcomes in patients with

cancer

b. DOACs should be first line as in patients due to superior outcomes in

reduction of recurrent VTE and a decreased risk of bleeding

c. DOACs seem to be at least safe and effective as convention anticoagulant

treatment in patients with cancer and VTE


Subgroup analysis and meta-analysis have found that DOACs maybe reasonable to

use in patients with VTE and cancer. There has only been one randomized

controlled trial with edoxaban that showed edoxaban was non-inferior to

tranditonal treatment, specifically with a decrease in recurrent VTE, but at the

increased risk of bleeding. Additional randomized trials will hopefully provide

more answers within the specific agents.


YA is a 47 y/o male with a PMH of myeloma who is diagnosed with a VTE. Despite

his myeloma, he is active and enjoys nights out where he tries various

restaurants. He understands that anticoagulation is needed, but does not like the

idea of injecting himself daily. He also states, while he doesn’t want to inject

himself daily, he also doesn’t want to use a drug that hasn’t been studied for

patients with cancer. Which of the following agents has been shown to be non-

inferior to traditional treatment with LMWH?

a. Apixaban

b. Betrixaban

c. Dabigatran

d. Edoxaban

e. Rivaroxaban


Currently, the only DOAC that has been studied and compared to a LMWH for

recurrent cancer-associated VTE is edoxaban (Hokusai VTE Cancer trial).

Apixaban has a trial that is currently ongoing (ADAM-VTE) and subgroup analysis

have been completed looking at various DOACs, but that data may be impacted

due to the small number of patients with active cancer and the comparative

agent being warfarin instead of LMWH.


DOACs have multiple indications and dosages so it is imperative as a pharmacist to ensure the right dose is given to a patient based on their indication.

CHEST recommends DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) over vitamin K antagonist for long-term anticoagulant treatment for non-cancer VTE patients. However, LMWH remain the recommended choice for long-term antithrombotic therapy.

While DOACs studies on VTE treatment included patients with cancer, it is important to note, those studies compared DOACs to warfarin instead of LMWHs.

The use of DOACs in patients with recurrent cancer associated VTE is on the rise and new data will be available in the near future that may change practice patterns significantly.

TAKE HOME POINTS

Stopping the Shot for Prevention of Clots: Oral

Options for Cancer-Associated Venous

ThromboembolismSamarth Shah, PharmD, BCPS



Yana Labinov, PharmD, BCPS



Yash Desai, PharmD Candidate

Roosevelt University College of Pharmacy

Stopping the Shot for Prevention of Clots: Oral · 2018. 9. 15. · Stopping the Shot for...

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