powerpoint presentation · 2019-09-19 · –dual antiplatelet in coronary artery disease 2016...

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The Role of Antithrombotic Therapy in End of Life Care

Myra Belgeri, Pharm.D, BCGP, BCPS, FASCP

Clinical Pharmacist, Optum Hospice Pharmacy Services

October 2019

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• I have no relevant financial relationships with manufacturers of any commercial products and/or providers of commercial services discussed in this presentation.

• This discussion will include the use of medications for off-label indications.

Disclosure

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• Review common antithrombotic therapy for outpatient use

• Identify potential risks and benefits of antithrombotic therapy

• Use risk tools, evidence-based medicine, and patient-specific factors to determine the appropriateness of antithrombotic therapy

Objectives

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• Which of the following statements is true?

A. Platelets do not play a role in thrombus formation

B. An anticoagulant drug decreases platelet aggregation

C. An antithrombotic drug can affect either the clotting cascade or platelet aggregation

D. The terms “anticoagulant” and “antiplatelet” are interchangeable and have the same definition

Question 1

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• Antithrombotic

– A drug or substance that reduces the formation of thrombi

• Anticoagulant

– Hinders coagulation of the blood by exerting its effects on the clotting cascade

• Antiplatelet

– Acts against platelets, destroys platelets, or decreases platelet aggregation

Definitions

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Platelet

Aggregation

Platelet comes in contact

with collagen

Activation of

Glycoprotein IIb/IIIa

receptor

Formation of

Thromboxane A2

Release of

ADP

Thrombin Fibrin

CLOT

Decrease

in cAMP

Role of Platelets in Thrombus Formation

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Clotting Cascade

XIIaXII

XI XIa

IX IXa

X Xa

PROTHROMBIN THROMBIN

FIBRINOGEN FIBRIN CLOT

VII

III

INTRINSIC PATHWAY

EXTRINSIC PATHWAY

VIIa

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• Atrial fibrillation (AF)

• Venous thromboembolism (VTE)

– Deep vein thrombosis (DVT), pulmonary embolism (PE)

• Valvular heart disease

• Ischemic stroke or transient ischemic attack (TIA)

• Coronary artery disease (CAD)

– Acute coronary syndromes (ACS) – unstable angina, ST-elevation myocardial infarction (STEMI), non-STEMI

– Percutaneous intervention (PCI) and coronary artery bypass graft (CABG)

• Peripheral arterial disease (PAD)

Indications for Antithrombotic Therapy

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A. Platelets do not play a role in thrombus formation

B. An anticoagulant drug decreases platelet aggregation

C. An antithrombotic drug can affect either the clotting cascade or platelet aggregation

D. The terms “anticoagulant” and “antiplatelet” are interchangeable and have the same definition

Question 1

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Antithrombotics for Outpatient Use

Antiplatelet Agents

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• Aspirin

• Aspirin/dipyridamole (Aggrenox®)

• ADP-receptor antagonists

– Clopidogrel (Plavix®)

– Prasugrel (Effient®)

– Ticagrelor (Brilinta®)

Antiplatelet Agents

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• Decreases platelet aggregation by inhibiting the formation of thromboxane A2

Mechanism

Of Action

Efficacy

• Decreases major vascular events by 20-30% in secondary prevention

• Lack of net benefit for routine primary prevention

• Reduces stroke incidence by 19% in atrial fibrillation

• Reduces risk of recurrent VTE by ~30%

• CAD, stroke/TIA, PAD, AF, VTEAntithrombotic

Uses

Aspirin

Common

Adverse

Effects

• Bleeding

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• Dipyridamole - inhibits platelet aggregation by inhibiting the activity of adenosine deaminase and phosphodiesterase

• Aspirin - decreases platelet aggregation by inhibiting the formation of thromboxane A2

Mechanism

Of Action

Efficacy• Reduction in recurrent stroke by ~20%

• Similar efficacy to aspirin and clopidogrel for recurrent stroke

• Ischemic stroke or TIA (secondary prevention) Antithrombotic

Uses

Aspirin/Dipyridamole (Aggrenox®)

Common

Adverse

Effects

• Bleeding, headache, abdominal pain, nausea, diarrhea

• More bleeding when compared to clopidogrel

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• Inhibit platelet activation and aggregation by binding to ADP receptors on platelets

• Available agents:

– Clopidogrel (Plavix®)

– Prasugrel (Effient®)

– Ticagrelor (Brilinta®)

ADP-Receptor Antagonists

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Drug Antithrombotic Uses Efficacy Adverse Effects

Clopidogrel (Plavix®)

ACS, CAD, PCI,

CABG, stroke, AF, PAD

• Better than aspirin alone in reducing

risk of vascular events

• In combination with aspirin:

▪ Significant decrease in mortality &

vascular events

▪ Better than aspirin alone in AF

▪ Less efficacious than warfarin in

AF

• Bleeding

• Thrombotic

thrombocytopenia

purpura (rare)

Prasugrel

(Effient®)

ACS undergoing PCI

Should be used with

aspirin 75-325 mg/day

• In combination with aspirin: Better than

clopidogrel in decreasing vascular

events and reducing stent thrombosis

• Bleeding (esp if ≥75

years old or <60Kg)

• Thrombotic

thrombocytopenia

purpura (rare)

• Boxed warning: Risk

of significant or fatal

bleeding

Ticagrelor

(Brilinta®)

ACS with PCI or CABG

History of MI

Should be used with

aspirin 75-100mg/day

• In combination with aspirin:

▪ Better than clopidogrel in

decreasing rates of MI and stent

thrombosis

▪ overall mortality by 22%

• Bleeding

• Dyspnea

• Boxed warning: Risk

of significant or fatal

bleeding

ADP-Receptor Antagonists

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Platelet

Aggregation

Platelet comes in contact

with collagen

Activation of

Glycoprotein IIb/IIIa

receptor

Formation of

Thromboxane A2

Release of

ADP

Thrombin Fibrin

CLOT

Decrease

in cAMP

Antiplatelet Sites of Action

CLOPIDOGRELPRASUGRELTICAGRELOR ASPIRIN

DIPYRIDAMOLE

Anticoagulants

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• A patient’s nutritional status is important to consider with which of the following anticoagulants?

A. Enoxaparin (Lovenox®)

B. Warfarin (Coumadin®, Jantoven®)

C. Dabigatran (Pradaxa®)

D. Apixaban (Eliquis®)

Question 2

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• Available agents for outpatient use

– Low molecular weight heparins

• Enoxaparin (Lovenox®), dalteparin (Fragmin®)

– Vitamin K antagonist

• Warfarin (Coumadin®, Jantoven®)

– Direct oral anticoagulants (DOACs)

• Direct thrombin inhibitor – dabigatran (Pradaxa®)

• Factor Xa inhibitors – apixaban (Eliquis®), edoxaban (Savaysa®), rivaroxaban (Xarelto®)

Anticoagulants

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• Inhibits factor Xa and thrombinMechanism

Of Action

Efficacy

• Decreases mortality and recurrence of VTE

• Possibly better than unfractionated heparin for VTE

• Better than or just as efficacious as unfractionated heparin for ACS

• Prevention and treatment of VTE

• Treatment of ACS and PCI

• Bridging therapy with oral anticoagulation (AF)

Antithrombotic

Uses

Low Molecular Weight Heparin (LMWH)

Adverse

Effects

• Bleeding/bruising, thrombocytopenia (uncommon), epidural or spinal hematoma (uncommon)

• Enoxaparin (Lovenox®)

• Dalteparin (Fragmin®)

Available

Agents

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• Decreases the formation of vitamin K-dependent clotting factors (prothrombin (II), VII, IX, X)

Mechanism

Of Action

Efficacy

• AF: Reduces risk of stroke by ~68%

• VTE: Reduces risk of recurrent VTE by ~90%

• Prosthetic valves: Reduces risk of valve thrombosis and thromboembolic events by ~80%

• Prevention and treatment of VTE

• Prevention of systemic embolism: AF, prosthetic heart valves,

acute myocardial infarction, valvular heart disease

Antithrombotic

Uses

Warfarin (Coumadin®, Jantoven®)

Adverse

Effects

• Bleeding/bruising, skin necrosis (uncommon), purple toe syndrome (uncommon)

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• Lab monitoring

– Prothrombin time (PT) / International Normalized Ratio (INR)

• Diet considerations: oral vitamin K intake

• Drug Interactions


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Examples of medications/drug classes that potentiate warfarin ( INR)

Acetaminophen

Alcohol

Amiodarone

Amoxicillin

Anti-inflammatory agents

Azithromycin

Azole antifungals

Cefazolin/cefotetan

Cimetidine

Chemotherapeutic agents

(tamoxifen, fluorouracil,

paclitaxel, gemcitabine)

Clarithromycin

Doxycycline

Erythromycin

Fluoroquinolones

Gemfibrozil

Metronidazole

Proton-pump inhibitors

Tetracycline

Tramadol

SSRIs

Statins

Trimethoprim/sulfamethoxazole

Examples of medications that inhibit warfarin ( INR)

Carbamazepine

Cholestyramine

Cyclosporine

Dicloxacillin

Phenobarbital

Rifampin

Ritonavir

Sucralfate

Vitamin K (phytonadione)

**Examples only – NOT a comprehensive list**

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• Direct thrombin inhibitor – dabigatran (Pradaxa®)

• Factor Xa inhibitors – apixaban (Eliquis®), edoxaban (Savaysa®), rivaroxaban (Xarelto®)

• No lab monitoring required for efficacy

• Renal disease dosage adjustments

• Black box warning

– Premature D/C increases risk of thrombotic events

– Spinal/epidural hematomas

• Studied vs. warfarin in AF and VTE

• Current studies evaluating efficacy in VTE with cancer

• No direct “head-to-head” comparison studies

Direct Oral Anticoagulants (DOACs)

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• Binds to and inhibits thrombinMechanism

Of Action

Efficacy

• Better than or just as effective as warfarin

• Increased risk of MI?

• Increased rates of thromboembolic events and bleeding with

valve replacement

• Prevention of stroke/systemic embolism in nonvalvular AF

• Treatment and/or prevention of VTE

Antithrombotic

Uses

Dabigatran (Pradaxa®)

Adverse

Effects

• Bleeding, dyspepsia

• More GI bleeding than warfarin

• Other minor and major bleeding similar to warfarin

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• Drug Interactions – avoid use with P-glycoprotein inhibitors and inducers (w/ lower CrCl)

– Inhibitors: ketoconazole*, dronedarone*, amiodarone, verapamil, clarithromycin, quinidine

– Inducers: rifampin

Dabigatran (Pradaxa®)

*May use lower dose of dabigatran with ketoconazole or dronedarone for nonvalvular AF

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• Inhibits factor XaMechanism

Of Action

Efficacy

• AF: apixaban and edoxaban better than warfarin; rivaroxaban just

as effective as warfarin

• VTE: abixaban, edoxaban, and rivaroxaban just as effective as warfarin

• CAD/PAD: low-dose rivaroxaban + aspirin decreases CV events

• See next slideAntithrombotic

Uses

Factor Xa Inhibitors

Adverse

Effects

• Bleeding

• Less major bleeding than warfarin: apixaban & edoxaban

• More GI bleeding than warfarin: rivaroxaban & edoxaban

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Factor Xa Inhibitors – Antithrombotic Uses

• Prevention of stroke or systemic embolism in nonvalvular AF

• Treatment and/or prevention of DVT/PE

• Prevention of VTE secondary to orthopedic surgery

Apixaban (Eliquis®)

Rivaroxaban(Xarelto®)



• Prevention of VTE secondary to orthopedic surgery

• Coronary artery disease or peripheral artery disease



Edoxaban(Savaysa®)

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• Drug Interactions – P-glycoprotein* and CYP 3A4

– Inhibitors: azole antifungals, protease inhibitors, dronedarone, amiodarone, verapamil, clarithromycin, quinidine

– Inducers: rifampin, phenytoin, carbamazepine, phenobarbital

Factor Xa Inhibitors

*Only P-glycoprotein for edoxaban

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Anticoagulant Sites of Action

XIIaXII

XI XIa

IX IXa

X Xa

PROTHROMBIN THROMBIN

FIBRINOGEN FIBRIN CLOT

VII

III

WARFARIN

LMWH

APIXABAN

EDOXABAN

RIVAROXABAN

DABIGATRAN

VIIa

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• A patient’s nutritional status is important to consider with which of the following anticoagulants?

A. Enoxaparin (Lovenox®)

B. Warfarin (Coumadin®, Jantoven®)

C. Dabigatran (Pradaxa®)

D. Apixaban (Eliquis®)

Question 2


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• Atrial fibrillation (AF)

• Venous thromboembolism (VTE)

– Deep vein thrombosis (DVT), pulmonary embolism (PE)

• Valvular heart disease

• Ischemic stroke or transient ischemic attack (TIA)

• Coronary artery disease (CAD)

– Acute coronary syndromes (ACS) – unstable angina, ST-elevation myocardial infarction (STEMI), non-STEMI

– Percutaneous intervention (PCI) and coronary artery bypass graft (CABG)

• Peripheral arterial disease (PAD)


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• CHEST guidelines

– Atrial fibrillation 2018

– Antithrombotic Therapy and Prevention of Thrombosis 2012

– Venous thromboembolism 2016

• American Heart Association/American College of Cardiology (AHA/ACC) guidelines

– Atrial fibrillation 2019

– Primary prevention 2019

– Dual antiplatelet in coronary artery disease 2016

– Peripheral arterial disease 2016

– Valvular heart disease 2017

• American Heart Association/American Stroke Association (AHA/ASA) guidelines

– Stroke and transient ischemic attack 2014

• American Society of Clinical Oncology (ASCO)

– VTE Prophylaxis and Treatment in Patients With Cancer: Clinical Practice Guideline 2015

• National Comprehensive Cancer Network (NCCN)

– Cancer-Associated Venous Thromboembolic Disease Guidelines 2019

Evidence-Based Guidelines

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• Antithrombotic therapy recommendations based on stroke risk

• CHA2DS2-VASc score

– Estimates risk of stroke in AF

– Used to identify patients that are low risk

Atrial Fibrillation

CCongestive

Heart Failure1

H Hypertension 1

A Age ≥ 75 years 2

D Diabetes 1

S Stroke or TIA 2

VVascular

Disease1

A Age 65-74 years 1

S

cSexual category 1

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Nonvalvular Atrial Fibrillation

CHA2DS2-VASc score Recommendation

MALE FEMALE

0 1 No Antithrombotic Therapy

≥ 1 ≥ 2

Stroke prevention with oral

anticoagulation:

• Dabigatran

• Apixaban

• Rivaroxaban

• Edoxaban

• Warfarin

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Type of Valvular Disease Recommended Antithrombotic

Moderate to severe mitral stenosis Warfarin

Native aortic valve disease,

tricuspid valve disease, or

mitral regurgitation

(with CHA2DS2-VASc score ≥ 2)

Warfarin

DOACs as an alternative

Atrial Fibrillation with Valvular Heart Disease

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Type of valve replacementRecommended

Antithrombotic TherapyINR range

Bioprosthetic (tissue) valve Warfarin x 3-6 months 2.0 - 3.0

Aortic mechanical bileaflet valve Warfarin life-long 2.0 - 3.0

Aortic single-tilting disc valve Warfarin life-long 2.0 - 3.0

Aortic mechanical valve plus risk factors for

thromboembolic events*Warfarin life-long 2.5 - 3.5

Aortic mechanical valve – older-generation

(e.g., ball-in-cage)Warfarin life-long 2.5 - 3.5

Mitral mechanical valve Warfarin life-long 2.5 - 3.5

Trans-catheter aortic valveWarfarin x 3 months -OR-

Aspirin 75-100 mg plus

clopidogrel 75 mg2.0 - 3.0

Prosthetic Valve Replacement

*AF, previous VTE, left ventricular dysfunction, hypercoagulable conditions

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• Recommended options:

1. DOAC

2. Warfarin

3. LMWH

• Duration of treatment

– Acute treatment: 3 months

– Extended treatment

• Provoked VTE : no therapy

• Unprovoked VTE: no scheduled stop date

Venous Thromboembolism (VTE)

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• Monotherapy:

– LMWH preferred (dalteparin, enoxaparin)

– Rivaroxaban

– Fondaparinux

– UFH IV or SC

– Apixaban*

• Combination therapy

– LMWH/UFH + edoxaban

– LMWH/UFH/fondaparinux + warfarin

– LMWH/UFH + dabigatran*

Cancer-Associated VTE

* if patient refuses or have compelling reasons to avoid LMWH

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• Non-cardioembolic stroke

1. Clopidogrel -OR- aspirin/dipyridamole

2. Low-dose aspirin

3. Cilostazol

• Cardioembolic stroke

– Same recommendations as AF

Stroke or TIA

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Coronary Artery Disease

Stable

CAD

No history of

MI, PCI, or

recent CABG

Bare metal

stent

Drug-eluting

stent

Aspirin +

clopidogrel

s/p PCI

s/p CABG

Aspirin +

clopidogrelfor at least 1 month

Aspirin +

clopidogrelfor at least 6 months

No Antiplatelet

therapy

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Coronary Artery Disease

Acute

or

Recent

ACS

Medical

management

Clopidogrel -OR-

Ticagrelor

Lytic therapy

PCI (Bare metal stent or

Drug-eluting stent)

CABGClopidogrel -OR-

Prasugrel -OR-

Ticagrelor

Taken with aspirin for at least 12 months

Clopidogrel -OR-

Prasugrel -OR-

Ticagrelor

Clopidogrel

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• Asymptomatic PAD

– Antiplatelet therapy may be considered

• Symptomatic PAD

– Single antiplatelet (aspirin or clopidogrel)

– DAPT may be reasonable after lower extremity revascularization

• Anticoagulation should not be used*

DAPT = dual antiplatelet therapy

Peripheral Arterial Disease

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Mr. X is an 86 year old male admitted to hospice for prostate cancer. He is being discharged from the hospital today. He lives at home with his wife, who is his primary caregiver.

PMH: bone metastases, acute DVT (related to cancer), CVA, depression

• According to the evidence-based guidelines, which antithrombotic regimen is the most appropriate for Mr. X’s cancer-associated DVT?

A. Aspirin alone

B. Aspirin plus clopidogrel

C. Warfarin alone

D. Rivaroxaban alone

Question 3

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Mr. X is an 86 year old male admitted to hospice for prostate cancer. He is being discharged from the hospital today. He lives at home with his wife, who is his primary caregiver.

PMH: bone metastases, acute DVT (related to cancer), CVA, depression

• According to the evidence-based guidelines, which antithrombotic regimen is the most appropriate for Mr. X’s cancer-associated DVT?

A. Aspirin alone

B. Aspirin plus clopidogrel

C. Warfarin alone

D. Rivaroxaban alone

Question 3

Risks and Benefits of Antithrombotic Therapy

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A. Warfarin has the greatest benefit if the patient has a high risk of stroke and a high risk of bleeding

B. Major/severe bleeding from antithrombotic therapy is managed with vitamin K

C. The full benefits of aspirin for preventing recurrent vascular events occur at 6 months of therapy

D. The risks of antithrombotic therapy always outweigh the benefits in hospice/palliative care

Question 4

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• No prior history of CAD – Framingham Risk Score

– Estimates 10-year risk of developing CHD

– Based on gender, age, total cholesterol, HDL cholesterol, antihypertensive therapy, systolic BP, smoker

• Existing CAD – risk of recurrent MI, stroke, cardiovascular death

– Up to 57% within the first year of initial event

– After 3 years, risk can be up to 40%

Risk of Major Vascular Events

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• Risk of an initial VTE = 0.1-0.2% per year

– Risk increases with age

• Risk of recurrence

– Provoked VTE – 1-5% after 1 year

– Unprovoked VTE – 10% after 1 year

– Cancer-related VTE – 15% per year

Risk of VTE

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Hypercoagulable state due to malignancy Surgery

Bedbound status or limited mobility Trauma

Increasing age Nephrotic syndrome

History of VTE Pregnancy

Genetic disorders (factor V Leiden, protein

C or S deficiencies)

Myeloproliferative disorders

Systemic lupus erythematosus Thrombophilia

Obesity Acute medical illness

Diseases that alter circulation • vessel wall abnormalities

• atherosclerotic heart disease

• vasculitis

• venous stasis/venous compression

• heart failure

• atrial fibrillation

• prosthetic heart valves

Medications • estrogen-containing oral contraceptives

• hormone replacement therapy

• selective estrogen receptor modulators

• erythropoiesis-stimulating agents

• cancer therapies (hormonal, chemotherapy,

radiotherapy)

Risk Factors for VTE or Ischemic Events

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1 year 6 months? 17.4 days?

Stroke Risk

No Therapy 4.5% 2.3% 0.21%

Warfarin 1.4% 0.7% 0.07%

Aspirin 3.2% 1.6% 0.15%

Absolute Risk Reduction in Stroke

Warfarin 2.7% 1.4% 0.13%

Aspirin 0.8% 0.4% 0.04%

Risk of Stroke in AF

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Factors that may increase risk of bleeding

Age > 65 years Liver disease

History of bleeding Renal insufficiency

History of peptic ulcers or GI bleed Recent surgery

Poor nutritional status Recent myocardial infarction

Variable appetite/nutrition intake Anemia, leukemia, multiple myeloma

Malignancy Previous stroke

Alcohol abuse Reduced functional capacity

Hypermetabolic states

(fever, hyperthyroidism)

Fat malabsorption syndromes/ impaired

absorption of vitamin K

Medications

(antiplatelets, anticoagulants, NSAIDs)

Concurrent medications that produce drug-

drug interactions

History of falls or high fall risk

(concomitant medications, orthostatic

hypotension, dementia, etc.)

Elevated HAS-BLED score

Risk of Bleeding

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HHypertension (SBP > 160

mmHg)1

AAbnormal renal and liver

function1 or 2

S Stroke 1

BBleeding

tendency/predisposition1

L Labile INRs (if on warfarin) 1

E Elderly (age > 65 years) 1

D Drugs or alcohol 1 or 2

Assessing Bleeding Risk

• Several risk stratification tools have been developed

• Useful for patients with a lower risk of thromboembolism

• HAS-BLED score

–Score > 3: high risk

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Antithrombotic Reversal Agent Other Interventions

Antiplatelets None • Platelet transfusion

LMWH IV protamine

Warfarin Vitamin K

• Fresh frozen plasma

• Prothrombin complex

concentrate

• Recombinant factor VIIa

DabigatranIdarucizumab

(Praxbind®)

• Dialysis

• Activated charcoal if within 2

hrs of ingestion

• Activated prothrombin complex

concentrate

Factor Xa InhibitorsAndexanet alpha

(Andexxa®)

• Activated charcoal if within 2

hrs of ingestion

• Activated prothrombin complex

concentrate

Management of Bleeding

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Number needed to treat (NNT) The number of patients that need to be treated in order for 1 patient to benefit

Clinical Benefits of Antithrombotic Therapy

Drug NNT NNH Comparator

Warfarin (AF) 13-37 in 1 year 24-833 Placebo

Aspirin

AF

Recurrent vascular

event

40-125 in 1 year

118 in 5 years

300

Placebo

DOACs (AF) 78-500 in ~2 years 101-1,000 Warfarin

Number needed to harm (NNH)The number of patients that need to be treated in order for 1 patient

to have an adverse event

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• Time to benefit

– Aspirin therapy for at least 10 years

– For VTE, within the first few days-weeks

– Risks decrease over time, bleeding risks remain same

• Net clinical benefit

– The impact of anticoagulation on ischemic complications vs. bleeding complications

– Warfarin – greatest benefit if high risk of stroke AND bleed

– DOACs have improved/higher net clinical benefit than warfarin

Clinical Benefits of Antithrombotic Therapy

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A. Warfarin has the greatest benefit if the patient has a high risk of stroke and a high risk of bleeding

B. Major/severe bleeding from antithrombotic therapy is managed with vitamin K

C. The full benefits of aspirin for preventing recurrent vascular events occur at 6 months of therapy

D. The risks of antithrombotic therapy always outweigh the benefits in hospice/palliative care

Question 4

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• A potential reason to continue antithrombotic therapy in a hospice patient is :

A. Preserved patient functional status

B. Variable or decreased nutritional status

C. Frequent medication changes

D. To extend patient’s survival

Question 5

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• Indication

• Symptoms

• Prognosis/functional status

• Bleeding risk

• Nutritional status

• Appropriate monitoring

• Medication adherence

• Medication changes

• Patient/family preferences

Hospice & Palliative Care Considerations

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• Decision-making considerations to NOT treat cancer-associated VTE:

– Patient refusal

– No therapeutic advantage

– No palliative benefit

– Unreasonable burden of anticoagulation

• Anticoagulation should not be used to extend survival in absence of other indications

Hospice & Palliative Care ConsiderationsNCCN and ASCO

NCCN = National Comprehensive Cancer NetworkASCO = American society of Clinical Oncologists

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Antithrombotic Considerations

Antiplatelets • No lab monitoring

• Prasugrel (Effient®) should be kept in original

container

• Newer agents – significant risk of bleeding, cost

LMWH • No lab monitoring

• Need to adjust dosing in renal impairment

• Injection

• Cost

Warfarin • No renal or hepatic dosing adjustments

• Lab monitoring

• Potentially complicated dosing regimen

• Drug-drug interactions

• Nutritional status


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Antithrombotic Considerations

Dabigatran • No lab monitoring


• Adherence

• Capsules should not be crushed

• Capsules should be kept in original container

• Cost

Factor Xa Inhibitors • No lab monitoring


• Adherence

• Complicated dosing adjustments for some

indications

• Drug-drug interactions

• Cost


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• Preserved functional status

• Cancer patients are at an increased risk of VTE

• Reduce the risk of unwanted sequelae related to thromboembolism

• Minimal or non-life-threatening bleeding

• Patient and family preference

Potential Reasons to Continue

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• Lack of indication

• Increased monitoring

• Negative impact on quality of life

• Bleeding complications

• Variable or decreased nutritional status

• Medication adherence

• Frequent medication changes

• Cost considerations

• Patient and family preference

Potential Reasons to Discontinue

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• A potential reason to continue antithrombotic therapy in a hospice patient is :

A. Preserved patient functional status

B. Variable or decreased nutritional status

C. Frequent medication changes

D. To extend patient’s survival

Question 5

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• Discuss on admission and continually reassess

• Provide options in potential changes in therapy

• Educate on patient decline (to help patient/family make their decision)

– Poor/declining renal function

– Decreased nutritional intake

– Swallowing status

– Increased bleeding risk

Preparing the Patient and Family

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• Antithrombotic medications are used to treat and/or prevent thrombosis or vascular events

• The risks and benefits of antithrombotic therapy should be discussed with the patient

• Several factors need to be considered when making decisions on continuing antithrombotic treatment

• The risk for thrombosis and bleeding should be reassessed frequently

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Questions

Myra Belgeri, Pharm.D., BCGP, BCPS, FASCP

Clinical Pharmacist, Optum Hospice Pharmacy Services

October 2019

[email protected]

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Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, Journal of the American College of Cardiology (2019), doi: https://doi.org/10.1016/j.jacc.2019.03.010.

Baber U, Mastoris I, Mehran R. Balancing ischaemia and bleeding risks with novel oral anticoagulants. Nat Rev Cardiol. 2014;11:693-703.

Banerjee A, Lane DA, Torp-Pedersen C, et al. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost. 2012;107(3): 584-589.

Braun LT, Grady KL, Kutner JS, et al. Palliative care and cardiovascular disease and stroke: a policy statement from the American Heart Association/American Stroke Association. Circulation. 2016;134:e198-e225.

Brunetti ND, Gesuete E, De Gennaro L, at al. Direct oral anti-coagulants compared with vitamin-K inhibitors and low-molecular-weight-heparin for the prevention of venous thromboembolism in patients with cancer: a meta-analysis study. Int J Cardiol. 2017;230:214-221.

Douros A, Durand M, Doyle CM, et al. Comparative effectiveness and safety of direct oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis of observational studies. Drug Saf. 2019 Jun 7. doi: 10.1007/s40264-019-00842-1. [Epub ahead of print]

Fahrni J, Husmann M, Gretener SB, et al. Assessing the risk of recurrent venous thromboembolism – a practical approach. Vasc Health Risk Manag. 2015;11:451-459.

Friberg L, Rosenqvist M, Lip GY. Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillationcohort study. Circulation. 2012; 125(19):2298-307.

Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary. Circulation. 2017;135:e686–e725.

Guyatt GH, Akl EA, Crowther M, et al. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2):7S-47S.

Hill RR, Martinez KD, Delate T, et al. A descriptive evaluation of warfarin use in patients receiving hospice or palliative care services. J Thromb Thrombolysis. 2009;27:334-339.

References

72

Holmes HM, Bain KT, Zalpour A, et al. Predictors of anticoagulation in hospice patients with lung cancer. Cancer. 2010;116:4817-4824.

Hsu JC, Hsieh CY, Yank YH, et al. Net clinical benefit of oral anticoagulants: a multiple criteria decision analysis. PLoS ONE. 2015;10(4):e0124806.

January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation, Journal of the American College of Cardiology (2019), doi: https://doi.org/10.1016/j.jacc.2019.01.011.

Johnson MJ, Noble SI, Maraveyas A. Antithrombotic therapy in palliative care. Adv Pall Med. 2009;8:95-100.

Kakkos SK, Kirkilesis GI, Tsolakis IA. Editor’s choice – efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials. Eur J Vasc Endovasc Surg. 2014;48(5):565-575.

Kalantzi KI, Tsoumani ME, Goudevenos IA, et al. Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives. Expert Rev Clin Pharmacol. 2012;5(3):319-336.

Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. CHEST2016;149(2):315-352.

Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160-236.

Kierner KA, Gartner V, Schwarz M, et al. Use of thromboprophylaxis in palliative care patients: a survey among experts in palliative care, oncology, intensive care, and anticoagulation. Am J Hosp Palliat Care. 2008;25(2):127-131.

Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-2962.

Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients

with coronary artery disease. J Am Coll Cardiol. 2016;68:1082–115.

References

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9/16/2019

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Lexicomp. Individual drug monographs www.crlonline.com. Accessed July 2017.

Lip GY, Banerjee A, Boriani G, et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline expert panel report. CHEST. 2018;154:1121-1201.

Lyman GH, Bohlke K, Khorana AA, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline Update 2014. J Clin Oncol. 2015; 33(6) 654-656.

National Comprehensive Cancer Network (NCCN). Cancer-associated venous thromboembolic disease version 1.2019. NCCN.org, https://www.nccn.org/professionals/physician_gls/pdf/vte.pdf. Accessed June 21, 2019.

Nishimura RA,Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease. Circulation. 2017;135:e1159–e1195.

Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2016;37(3):267-315.

Sardar P, Chatterjee S, Mukherjee D. Efficacy and safety of new oral anticoagulants for extended treatment of venous thromboembolism: systematic review and meta-analysis of randomized controlled trials. Drugs. 2013;73:1171-1182.

Sheard L, Prout H, Dowding D, et al. The ethical decisions UK doctors make regarding advanced cancer patients at end of life – the perceived (in)appropriateness of anticoagulation for venous thromboembolism: a qualitative study. BMC Med Ethics. 2012;13:22.

Shoeb M, Fang MC. Assessing bleeding risk in patients taking anticoagulants. J Thromb Thrombolysis. 2013;35(3):312-319.

Spiess JL. Can I stop the warfarin? A review of the risks and benefits of discontinuing anticoagulation. J Palliat Med. 2009;12:83-87.

Tardy B, Picard S, Guirimand F, et al. Bleeding risk of terminally ill patients hospitalized in palliative care units: the RHESO study. J Thromb Haemost 2017; 15(3): 420-428.

References

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powerpoint presentation · 2019-09-19 · –dual antiplatelet in coronary artery disease 2016...

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