powerpoint presentation · 2019-09-19 · –dual antiplatelet in coronary artery disease 2016...
TRANSCRIPT
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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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• 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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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
Warfarin (Coumadin®, Jantoven®)
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Warfarin (Coumadin®, Jantoven®)
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 stroke or systemic embolism in nonvalvular AF
• Treatment and/or prevention of DVT/PE
• Prevention of VTE secondary to orthopedic surgery
• Coronary artery disease or peripheral artery disease
• Prevention of stroke or systemic embolism in nonvalvular AF
• Treatment and/or prevention of DVT/PE
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
Indications for Antithrombotic Therapy
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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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• 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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• Which of the following statements is true?
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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• Which of the following statements is true?
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
Hospice & Palliative Care Considerations
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Antithrombotic Considerations
Dabigatran • No lab monitoring
• Need to adjust dosing in renal impairment
• Adherence
• Capsules should not be crushed
• Capsules should be kept in original container
• Cost
Factor Xa Inhibitors • No lab monitoring
• Need to adjust dosing in renal impairment
• Adherence
• Complicated dosing adjustments for some
indications
• Drug-drug interactions
• Cost
Hospice & Palliative Care Considerations
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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
68
• 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
69
• 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
Key Points
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Questions
Myra Belgeri, Pharm.D., BCGP, BCPS, FASCP
Clinical Pharmacist, Optum Hospice Pharmacy Services
October 2019
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