9/16/2019 1 1 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 2 • 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 3 • 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 1 2 3
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
9/16/2019
1
1
The Role of Antithrombotic Therapy in End of Life Care
• 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
3
• 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
1
2
3
9/16/2019
2
4
• 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
5
• 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
6
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
4
5
6
9/16/2019
3
7
Clotting Cascade
XIIaXII
XI XIa
IX IXa
X Xa
PROTHROMBIN THROMBIN
FIBRINOGEN FIBRIN CLOT
VII
III
INTRINSIC PATHWAY
EXTRINSIC PATHWAY
VIIa
8
• Atrial fibrillation (AF)
• Venous thromboembolism (VTE)
– Deep vein thrombosis (DVT), pulmonary embolism (PE)
• Valvular heart disease
• Ischemic stroke or transient ischemic attack (TIA)
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
37
38
39
9/16/2019
14
40
• 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)
41
• 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
42
• Non-cardioembolic stroke
1. Clopidogrel -OR- aspirin/dipyridamole
2. Low-dose aspirin
3. Cilostazol
• Cardioembolic stroke
– Same recommendations as AF
Stroke or TIA
40
41
42
9/16/2019
15
43
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
44
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
45
• 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
43
44
45
9/16/2019
16
46
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
47
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
46
47
48
9/16/2019
17
49
• 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
50
• 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
51
• 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
49
50
51
9/16/2019
18
52
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
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
70
71
72
9/16/2019
25
73
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.