Download Oral Anticoagulation in Older Persons

2013/04/29
Oral Anticoagulation in Older Persons
The Next Generation
Luis Viana
B.Sc. Phm., Pharm D (candidate), M.Ed., ACPR, CGP
Clinical Consultant Pharmacist, Medical Pharmacies Group Limited
Adjunct Clinical Assistant Professor, School of Pharmacy, University of Waterloo
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
Speaker Disclosure Form
Luis Viana
“I have not in the past 2 years, had a financial interest,
arrangement or affiliation with one or more organizations
that could be perceived as a direct/indirect conflict of
interest in the content of the subject of this or any other
program.”
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
A Pragmatic Approach
Pragmatist:
• one who defines a proposition as true if it works
satisfactorily
• one who believes in practical solutions and
empirical evidence
• discards beliefs that have no rational basis
http://answers.ask.com/Society/Philosophy/what_is_pragmatism
Ali A, Bailey C, Abdelhafiz AH. Aging and Disease 2012:3:339-51.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
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2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
A Pragmatic Approach
A "pragmatic" approach focuses on the
question,
"What is the better treatment in the particular
clinical circumstances of the patients?"
Schwartz D, Lellouch J. J Clin Epidemiol 2009;62:499-505.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
A Pragmatic Approach
1. Should the patient receive oral
anticoagulation?
2. Which anticoagulant should be prescribed
“in the particular clinical circumstances of
the patient?"
Ali A, Bailey C, Abdelhafiz AH. Aging and Disease 2012;3:339-51.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate?
• prevention and treatment of venous
thrombosis/pulmonary embolus
• prevention and treatment of
thromboembolism due to atrial fibrillation
or prosthetic heart valve
• prevention of reinfarction and
thromboembolism post-MI
PL Detail-Document, Comparison of Oral Antithrombotics. Pharmacist’s Letter/Prescriber’s Letter. February 2013.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
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ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate?
STROKE
(ischemic)
http://www.hearthealthywomen.org/am-i-at-risk/featured/atrial-fibrillation-page-2.html
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate?
Clinical conditions associated with stroke:
• atrial fibrillation
• left ventricular dysfunction
• prosthetic heart valves
Sinnaeve PR, Brueckmann M, Clemens A, et al. J Intern Med 2012;271:15-24
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate?
Rate of
thromboembolic
events by age
(annual rate per 100)
Sinnaeve PR, Brueckmann M, Clemens A, et al. J Intern Med 2012;271:15-24
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
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2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate?
Atrial fibrillation (AF):
• highly prevalent in older adults
• 1.5% of adults aged 60 to 70 years
• 10% of adults aged >80 years
• risk of stroke or TIA is 4-5 times greater in patients
with AF
Sinnaeve PR, Brueckmann M, Clemens A, et al. J Intern Med 2012;271:15-24
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate?
Prevalence of
atrial fibrillation
by age
Sinnaeve PR, Brueckmann M, Clemens A, et al. J Intern Med 2012;271:15-24
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate?
Atrial fibrillation (AF):
• in older persons, strokes in AF are more severe
and disabling, and associated with high mortality
• ~50% at 1 year
• any risk score will place the average older adult
with AF in a high risk category, favouring the use
of anticoagulation
Sinnaeve PR, Brueckmann M, Clemens A, et al. J Intern Med 2012;271:15-24
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
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ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate?
Risk scores:
CHADS2
CHA2DS2VASC
Sinnaeve PR, Brueckmann M, Clemens A, et al. J Intern Med 2012;271:15-24
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate?
Risk scores: CHADS2
Grewal J, Farouque O. J Pharm Pract Res 2012;42:228-34.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate?
Risk scores: CHA2DS2VASc
Grewal J, Farouque O. J Pharm Pract Res 2012;42:228-34.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
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ORAL ANTICOAGULATION IN OLDER PERSONS
Warfarin – the gold standard for 60 years
Fatal bleeding in cattle in the 1920s after
eating mouldy silage made from sweet clover
•
•
•
•
1940 – anticoagulant in sweet clover isolated
1948 – warfarin synthesized
1952 – warfarin approved as rat poison
1954 – warfarin approved for human use
+
arin (from coumarin)
Pirmohamed M. Br J Clin Pharmacol 2006;62:509-511.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate with Warfarin?
Warfarin in non-valvular atrial fibrillation (NVAF):
• efficacy of oral anticoagulation is maintained
across all age groups, even the very old (> 85 years)
• efficacy of oral anticoagulation is maintained
across all CHADS2 scores even in those with low
risk (CHADS2 score 1-2)
Ali A, Bailey C, Abdelhafiz AH. Aging and Disease 2012;3:339-51.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate with Warfarin?
Warfarin in non-valvular atrial fibrillation (NVAF):
• the greatest net clinical benefit of oral
anticoagulation is observed in those > 85 years
old due to their high base line stroke risk
• good quality of INR control is achievable
regardless of age
Ali A, Bailey C, Abdelhafiz AH. Aging and Disease 2012;3:339-51.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
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2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Why Anticoagulate with Warfarin?
Warfarin in non-valvular atrial fibrillation (NVAF):
• aspirin has very little benefit in stroke risk
reduction in patients with NVAF and this benefit
tends to be attenuated further in old age
• oral anticoagulation therapy remains superior to
the combination of antiplatelet agents
Ali A, Bailey C, Abdelhafiz AH. Aging and Disease 2012;3:339-51.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Underuse of Warfarin in Older Persons
Statistics:
• > 85 years: 1 in 3 eligible patients were receiving
warfarin on admission for stroke
• may have valid reason to avoid warfarin
• patient refusal, non-compliance with INR monitoring, bleeding
diathesis, history of major bleeding or significant, alcohol
consumption
• < 75 years old: 3 out of 4 eligible patients were
receiving warfarin on admission for stroke
Partington SL, Abid S, Teo K, et al. Thromb Res 2007;120:663-9.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Underuse of Warfarin in Older Persons
Reasons:
• underestimation of thromboembolic risk
• overestimating bleeding risk
• intracranial hemorrhage
•
•
•
•
frailty
falls risk
need for monitoring
cognitive impairment
•
•
•
•
history of non-adherence
advanced illness
malignancy
advanced age
Sinnaeve PR, Brueckmann M, Clemens A, et al. J Intern Med 2012;271:15-24
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
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2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Underuse of Warfarin in Older Persons
Reasons:
• bleeding risk
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Alternatives to Warfarin
The development of novel oral anticoagulants,
such as direct thrombin inhibitors (DTI’s) and
factor Xa inhibitors, may provide a safer and
more effective alternative for stroke
prevention .
Sinnaeve PR, Brueckmann M, Clemens A, et al. J Intern Med 2012;271:15-24
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Oral Anticoagulants
Vitamin K
Antagonists
Warfarin
New Oral
Anticoagulants
Direct Thrombin
Inhibitors
Factor Xa
Inhibitors
dabigatran
rivaroxaban
apixaban
edoxaban
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
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ORAL ANTICOAGULATION IN OLDER PERSONS
Oral Anticoagulants – Mechanism of Action
rivaroxaban, apixaban
Factor Xa inhibitors
warfarin
dabigatran
Direct Thrombin Inhibitor
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Major results of phase 3 trials of NGOA
compared to warfarin in atrial fibrillation
Drug/Trial
Stroke or
Hemorrhagic
thromboembolism stroke
Major
bleeding
dabigatran (RE-LY)
34% reduction
74%
reduction
similar
rivaroxaban (ROCKET-AF)
non-inferior to
warfarin
40%
reduction
similar
apixaban (ARISTOTLE)
20% reduction
50%
reduction
30%
reduction
Connolly SJ, Ezekowitz MD, Yusuf S, et al. N Engl J Med 2009;361:1139-51. (RE-LY)
Patel MR, Mahaffey KW, Garg J, et al. N Engl J Med 2011;365:883-91. (ROCKET-AF)
Granger CB, Alexander JH, McMurray JJ, et al. N Engl J Med 2011;365:981-92. (ARISTOTLE)
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Class effects compared with warfarin
• efficacy
• non inferior or possibly better than warfarin in
terms of prevention of ischemic/hemorrhagic
stroke or systemic embolism
• less intracranial bleeding than warfarin
Connolly SJ, Ezekowitz MD, Yusuf S, et al. N Engl J Med 2009;361:1139-51. (RE-LY)
Patel MR, Mahaffey KW, Garg J, et al. N Engl J Med 2011;365:883-91. (ROCKET-AF)
Granger CB, Alexander JH, McMurray JJ, et al. N Engl J Med 2011;365:981-92. (ARISTOTLE)
Weitz JI, Gross PL. Hematology Am Soc Hematol Educ Program. 2012;2012:536-40.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
9
2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Class effects compared with warfarin
• trend for reduced mortality compared with
warfarin
• no hepatic toxicity
Connolly SJ, Ezekowitz MD, Yusuf S, et al. N Engl J Med 2009;361:1139-51. (RE-LY)
Patel MR, Mahaffey KW, Garg J, et al. N Engl J Med 2011;365:883-91. (ROCKET-AF)
Granger CB, Alexander JH, McMurray JJ, et al. N Engl J Med 2011;365:981-92. (ARISTOTLE)
Weitz JI, Gross PL. Hematology Am Soc Hematol Educ Program. 2012;2012:536-40.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Differentiating effects compared with warfarin
• dabigatran
• small increase in risk of myocardial infarction
compared to warfarin
• dabigatran and rivaroxaban
• more gastrointestinal bleeding than with
warfarin
Connolly SJ, Ezekowitz MD, Yusuf S, et al. N Engl J Med 2009;361:1139-51. (RE-LY)
Patel MR, Mahaffey KW, Garg J, et al. N Engl J Med 2011;365:883-91. (ROCKET-AF)
Weitz JI, Gross PL. Hematology Am Soc Hematol Educ Program. 2012;2012:536-40.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Differentiating effects compared with warfarin
• dabigatran (150 mg po bid)
• lower risk of ischemic stroke than warfarin
• apixaban
• lower risk of stroke and major bleeding
compared with warfarin
Connolly SJ, Ezekowitz MD, Yusuf S, et al. N Engl J Med 2009;361:1139-51. (RE-LY)
Granger CB, Alexander JH, McMurray JJ, et al. N Engl J Med 2011;365:981-92. (ARISTOTLE)
Weitz JI, Gross PL. Hematology Am Soc Hematol Educ Program. 2012;2012:536-40.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
10
2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Summary of characteristics compared to
warfarin
Feature
Warfarin
Next Generation Oral Anticoagulants
Onset
Slow
Rapid
Dosing
Variable
Fixed
Food effect
(vitamin K rich foods)
Yes
No
Drug interactions
Many
Some
Monitoring
Yes
No
Offset
Long
Shorter
Antidote
Yes
No
Weitz JI, Gross PL. Hematology Am Soc Hematol Educ Program. 2012;2012:536-40.
27th
Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Pharmacokinetics
Feature
Warfarin
Dabigatran Rivaroxaban
Apixaban
Bioavailability
100%
6%
60-80%
60%
Dosing
once daily
twice daily
once or twice twice daily
daily
Time to peak effect
4-5 days
1-3 hrs
2-4 hrs
1-2 hrs
Half-life
40 hrs
8-15 hrs
7-11 hrs
12 hrs
Renal clearance
none
80%
33%
25%
Drug interactions
multiple
P-gp
3A4/P-gp
3A4/P-gp
Weitz JI, Gross PL. Hematology Am Soc Hematol Educ Program. 2012;2012:536-40.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Indications (Canada)
Indication
Warfarin Dabigatran
Rivaroxaban Apixaban
Prevention of thromboembolism
(stroke) in NVAF
YES
YES
YES
YES
Prevention of thromboembolism
(stroke) with prosthetic heart
valve
YES
NO
NO
NO
Prevention of thromboembolism
(stroke) in patients who have
undergone elective THR or TKR
YES
YES
YES
YES
Treatment of venous
YES
NO
YES
thromboembolic events (DVT &
PE) and prevention of recurrent
DVT and PE
Pradaxa™
(product monograph). Boehringer Ingelheim Canada Ltd. January 27, 2012.
NO
Xarelto® (product monograph). Bayer Inc. April 12, 2013.
Eliquis™ (product monograph). Pfizer Canada Inc. November 27, 2012.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
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2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Indication and Dosage (Canada)
Indication
Dabigatran (Pradax™)
Prevention of thromboembolism
(stroke) in NVAF
150 mg po twice daily (CrCl > 30 mL/min)
110 mg po twice daily (> 80 years old)
Prevention of thromboembolism
(stroke) with prosthetic heart valve
NOT INDICATED
Prevention of thromboembolism
(stroke) in patients who have
undergone elective THR or TKR
220 mg (2 x 110 mg) po once daily
150 mg (2 x 75 mg) po once daily (> 75 years old)
75 mg (initial dose 1-4 hrs post-op), then 150 mg po once daily
(CrCl 30-50 mL/min)
Treatment of venous thromboembolic
events (DVT & PE) and prevention of
recurrent DVT and PE
NOT INDICATED
Severe renal impairment (CrCl < 30 mL/min) – contraindicated
Pradax™ (product monograph). Boehringer Ingelheim Canada Ltd. January 27, 2012.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Indication and Dosage (Canada)
Indication
Rivaroxaban (Xarelto®)
Prevention of thromboembolism
(stroke) in NVAF
20 mg po once daily with food (CrCl > 50 mL/min)
15 mg po once daily (CrCl = 30-49 mL/min)
Prevention of thromboembolism
(stroke) with prosthetic heart valve
NOT INDICATED
Prevention of thromboembolism
(stroke) in patients who have
undergone elective THR or TKR
10 mg po once daily (initial dose given with 6-10 hrs post-op)
• THR – give for 35 days
• TKR – give for 14 days
Treatment of venous thromboembolic
events (DVT & PE) and prevention of
recurrent DVT and PE
15 mg po bid for first 3 weeks, then 20 mg po once daily
Severe renal impairment (CrCl < 30 mL/min) – contraindicated
Xarelto® (product monograph). Bayer Inc. April 12, 2013.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Indication and Dosage (Canada)
Indication
Apixaban (Eliquis™)
Prevention of thromboembolism
(stroke) in NVAF
5 mg po bid (> 25 mL/min)
2.5 mg po bid (if patient has at least 2 of the following:
• age > 80 years, body weight < 60 kg, serum creatinine > 133
mmol/L
Prevention of thromboembolism
(stroke) with prosthetic heart valve
NO
Prevention of thromboembolism
(stroke) in patients who have
undergone elective THR or TKR
2.5 mg po bid (initial dose to be taken 12-24 hrs post-op)
• THR – give for 32-38 days
• TKR – give for 10-14 days
Treatment of venous thromboembolic
events (DVT & PE) and prevention of
recurrent DVT and PE
NO
Severe renal impairment (CrCl < 15 mL/min) – contraindicated
Eliquis™ (product monograph). Pfizer Canada Inc. November 27, 2012.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
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2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Drug Interactions
Mechanism
Dabigatran
Rivaroxaban
Apixaban
CYP 3A4
NO
YES
YES/NO
P-glycoprotein (P-gp)
YES
YES
YES
CYP 3A4
• involved with metabolism of many drugs
P-gp
• intestinal efflux transporter of many drugs
CYP 3A4 + P-gp interactions are a concern
Walenga JM, Adiguzel C. Int J Clin Pract 2010;64:835-8.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Drug Interactions
• antiplatelet agents (increased bleeding risk)
• aspirin, clopidogrel
• NSAID’s (increased bleeding risk)
• naproxen, diclofenac
Walenga JM, Adiguzel C. Int J Clin Pract 2010;64:835-8.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Drug Interactions – dabigatran
• P-gp inhibitors (↑ levels, ↑ anticoagulant effect)
• verapamil, dronaderone, quinidine, amiodarone,
ketoconazole
• CYP 3A4 + P-gp inhibitors (↑ levels, ↑ anticoagulant effect)
• clarithromycin
• CYP 3A4 + P-gp inducers (↓ levels, ↓ anticoagulant effect)
• rifampin, St. John’s Wort, pantoprazole
Pradaxa™ (product monograph). Boehringer Ingelheim Canada Ltd. January 27, 2012
Walenga JM, Adiguzel C. Int J Clin Pract 2010;64:835-8.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
13
2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Drug Interactions – dabigatran
• antacids (↓ levels, ↓ anticoagulant effect)
• administer dabigatran 2 hrs before taking antacid
• pantoprazole (↓ levels, ↓ anticoagulant effect)
• dabigatran absorption is pH dependent
• peak concentrations reduced by 11-54% when given
with pantoprazole 40 mg po bid
• clinical significance is unclear
Pradaxa™ (product monograph). Boehringer Ingelheim Canada Ltd. January 27, 2012
Walenga JM, Adiguzel C. Int J Clin Pract 2010;64:835-8.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Drug Interactions – rivaroxaban
• CYP 3A4 + P-gp inhibitors (↑ levels, ↑ anticoagulant effect)
• clarithromycin
• ketoconazole, itraconzole, voriconazole
• ritonavir
• CYP 3A4 + P-gp inducers (↓ levels, ↓ anticoagulant effect)
• rifampin, St. John’s Wort
• phenytoin, carbamazepine, phenobarbital
Xarelto® (product monograph). Bayer Inc. April 12, 2013.
Walenga JM, Adiguzel C. Int J Clin Pract 2010;64:835-8.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Drug Interactions – apixaban
• limited information available
• CYP 3A4 + P-gp inhibitors (↑ levels, ↑ anticoagulant effect)
• ketoconazole, itraconazole
• diltiazem, amiodarone, dronaderone
• CYP 3A4 + P-gp inducers (↓ levels, ↓ anticoagulant effect)
• rifampin, St. John’s Wort
• phenytoin, carbamazepine, phenobarbital
Xarelto® (product monograph). Bayer Inc. April 12, 2013.
Walenga JM, Adiguzel C. Int J Clin Pract 2010;64:835-8.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
14
2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Choice of anticoagulant based on patient characteristics
Characteristic
Drug Choice
Rationale
Mechanical valve or valvular atrial
fibrillation
warfarin
next generation oral anticagulants not
studied
Liver dysfunction with increased
INR
warfarin
new agents require hepatic
metabolism
Poor compliance
warfarin or nothing
missed doses of greater consequence
with shorter acting new agents
Stable on warfarin
warfarin
consider switching at patient request
CrCl < 30 mL/min
warfarin
safety for persons with significant
renal dysfunction has not been
established
CrCl 30-50 mL/min
rivaroxaban, apixaban
oral factor Xa inhibitors are less
affected by impaired renal function
than dabigatran
Weitz JI, Gross PL. Hematology Am Soc Hematol Educ Program. 2012;2012:536-40.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Choice of anticoagulant based on patient characteristics
Characteristic
Drug Choice
Rationale
Cannot swallow medication whole
warfarin, rivaroxaban or
apixaban
dabigatran must be swallowed whole
• capsule cannot be opened
Recent GI bleed
apixaban
more GI bleeding with dabigatran
(150 mg po bid) or rivaroxaban than
with warfarin
Recent ischemic stroke on warfarin
dabigatran
dabigatran (150 mg po bid)
associated with lower risk of ischemic
stroke than warfarin
Recent acute coronary syndrome
rivaroxaban or apixaban
slight increased risk of MI with
dabigatran
Poor compliance with twice daily or
request for a once daily regimen
rivaroxaban
only agent given once daily
Weitz JI, Gross PL. Hematology Am Soc Hematol Educ Program. 2012;2012:536-40.
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
15
2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Final Considerations:
• conversion to or from warfarin:
• dependant on renal function
• see individual product monographs for detailed
information
• stop before elective surgery
• dependant on renal function
• see individual product monographs for detailed
information
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
Final Considerations:
• consider the possibility of clinically significant drug
interactions
• clinical effect of drug interaction may not be apparent
• with warfarin, dose adjust based on change in INR
• no antidote
• with warfarin, use vitamin K
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
WARFARIN
DABIGATRAN
RIVAROXABAN
APIXABAN
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
16
2013/04/29
ORAL ANTICOAGULATION IN OLDER PERSONS
Next Generation Oral Anticoagulants
QUESTIONS
27th Annual Geriatric Medicine Refresher Day
May 1, 2013 • London Convention Centre, London, Ontario
17