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Better care, better population health and lower costs through improvement. Use of Anticoagulants in Geriatrics: Current Evidence and Special Considerations Aryn You, PharmD Assistant Professor, Pharmacy Practice The Daniel K. Inouye College of Pharmacy Aida Wen, MD Associate Professor, Department of Geriatric Medicine The John A Burns School of Medicine

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Page 1: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Better care, better population health and lower costs through improvement.

Use of Anticoagulants in Geriatrics: Current Evidence and Special Considerations

Aryn You, PharmDAssistant Professor, Pharmacy Practice

The Daniel K. Inouye College of Pharmacy

Aida Wen, MDAssociate Professor, Department of Geriatric Medicine

The John A Burns School of Medicine

Page 2: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Collaboration

JABSOM • – Geriatric Workforce Enhancement Program

Mountain• -Pacific Quality Health

The Daniel K. Inouye College of Pharmacy: •University of Hawaii at Hilo

Page 3: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

1.0 AMA PRA Category 1 Credits™

Page 4: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Participation & Evaluation• Evaluation and requests for credit are sent via email

after the activity– Those requesting CPE are required to participate in

the entire activity– Physicians requesting CME should claim only the

credit commensurate with the extent of their participation in the activity.

If you have any questions regarding the CME / CPE credit email, follow up with [email protected]

Page 5: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Financial Disclosures• DKICP Disclosures: Dr. Wen has disclosed

that she holds stock with Pfizer. All other speakers have no relevant financial relationships to disclose. All planning committee members and Continuing Education staff from the University of Hawai`i Hilo College of Pharmacy have no relevant financial relationships to disclose.

Page 6: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Better care, better population health and lower costs through improvement.

Use of Anticoagulants in Geriatrics:Learning Objectives and Case Study

Aida Wen, MDAssociate Professor, Department of Geriatric Medicine

The John A Burns School of Medicine

Page 7: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Learning Objectives• Identify patient factors that may influence the

decision to use therapeutic anticoagulants• Discuss patient populations that may be at

increased risk of adverse effects associated with anticoagulants

• Highlight differences between individual anticoagulant agents

Page 8: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Patient Case: James 83 • year old male HPI: Presents with difficulty breathing on exertion and is •found to have new onset Atrial Fibrillation and CHFPast Medical History: •

HTN–GERD–Arthritis–Anemia–Chronic Kidney Disease (Stage – 3)

Page 9: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Patient Case: James• Vitals:

– BP: 160/90, P: 90 bpm (Irregular), O2 Sat: 92% RAWt : 62kg, Ht 72in, BMI: 18.3

• Exam: – Alert, NAD, Heart - irregularly irregular, Lungs - scattered

crackles and wheezing, Abdomen - soft, Extremities - trace pedal edema

– Gait - steady, but Timed Get up and Go test = 30 sec (INCREASED RISK FOR FALL)

• Studies: – Stool guaiac neg. Hb 10.5, Cr. 2.0, CXR- mild CHF, EKG

Afib.

Page 10: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Patient Case: James• Medications:

– Metoprolol Succinate 50 mg PO daily– Acetaminophen 1000 mg PO BID– Ranitidine (Zantac) 150 mg PO daily

• Social: – He is a married, retired lawyer. He helps care for his

two young grandchildren, picking them up from school every day and helping with homework. Enjoys social drinking and playing the ukulele.

• GOAL: Remain independent

Page 11: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Atrial Fibrillation• Prevalence increases with Age

– >60 years of age: 4%– >80 years of age: 10%

• 71% of strokes occur in patients >70 years of age

Page 12: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Incidence of Atrial Fibrillation

Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. JAMA. 2001 May 9;285(18):2370-5.

Page 13: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

WHAT IS JAMES’ RISK OF STROKE?

Page 14: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Better care, better population health and lower costs through improvement.

Use of Anticoagulants in Geriatrics:Current Evidence and Special Considerations

Aryn You, PharmDAssistant Professor, Pharmacy Practice

The Daniel K. Inouye College of Pharmacy

Page 15: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

CHA2DS2-VASc• CHF History (1 point)• Hypertension (1 point)• Age > 75 years old (2 points)• Diabetes Mellitus• Stroke or Prior TIA• Vascular Disease• Age: 64-74 years old• Sex• TOTAL: 4 points (High Risk):

– Stroke risk: 4.8% per year – 6.7% risk of stroke/ TIA/ systemic embolism

Page 16: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Antithrombotic Recommendations

• CHEST 9th Edition (2012)– Patients with CHA2DS2-VASc ≥2: Dabigatran

rather than Warfarin (2B)• ACC/AHA/HRS Guidelines 2014

– Warfarin (1A)– Dabigatran, Rivaroxaban, Apixaban (1B)

Page 17: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Antithrombotic Therapy• Antithrombotic therapy is associated with

– 67% reduction in stroke/systemic embolism– 65% reduction in ischemic stroke– 26% reduction in mortality

• Only 25-55% of eligible patients receive therapy

• 70% discontinue therapy within 12 months

Page 18: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Antithrombotic Therapy in Elderly

14% Reduction in Warfarin use with each decade of age

Brophy MT, Snyder KE, Fiore LD, et al. Anticoagulant Use for Atrial Fibrillation in Elderly. JAGS 2004(52): 1151-1156

Page 19: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Oral AnticoagulantsWarfarin ● (Coumadin®, Jantoven®)NOAC = DOAC●

Novel Oral Anticoagulants = Direct Oral AnticoagulantsDabigatran ○ (Pradaxa®)Rivaroxaban ○ (Xarelto®)Apixaban ○ (Eliquis®)Edoxaban ○ (Savaysa®)Betrixaban ○ (Bevyxxa®)

Page 20: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Mechanism of Action

Page 21: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Timeline of FDA-Approvals

Page 22: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Bleeding-Related Readmissions● Warfarin is one of the top medications to cause

hospital readmissions

● Trials that led to DOAC FDA-approval showed overall decreased bleeding rates compared to warfarin

● Does real-world data support this?○ Low-quality, retrospective reviews have been

conducted○ Scarce evidence focusing on the elderly

population

Page 23: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Bleeding-Related Readmissions

WHAT IS JAMES’ RISK OF

BLEEDING?

Page 24: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

HAS-BLEDHypertension • (1 point)Renal Disease • (1 point)Liver Disease•Stroke History•Prior major bleeding or predisposition to bleeding • (1 point)Labeled INR•Age > • 65 years old (1 point)Medications that increase risk of bleed •Alcohol Use•TOTAL: • 4 points (HIGH):

8.9– % risk of bleed

Page 25: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Predicting Bleeds in Elderly

Poli D, Antonucci E, Palareti G, et al. Bleeding Risk in Very Old Patients on Vitamin K Antagonist Treatment: Results of a Prospective Collaborative Study on Elderly Patients Followed by Italian Centres for Anticoagulation. Circulation. 2011 (124): 824-829

Page 26: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Poli D, Antonucci E, Palareti G, et al. Bleeding Risk in Very Old Patients on Vitamin K Antagonist Treatment: Results of a Prospective Collaborative Study on Elderly Patients Followed by Italian Centres for Anticoagulation. Circulation. 2011 (124): 824-829

Page 27: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Predicting Bleeds in Elderly

Weak Correlation

with Conventional Risk Factors

Poli D, Antonucci E, Ageno W, et al. The Predictive ability of bleeding risk stratification models in very old patients on vitamin K antagonist treatment for venous thromboembolism: results of the prospective

collaborative EPICA study. J Thromb Haemost 2013; 11: 1053-8

Page 28: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Predicting Bleeds in Elderly

Poli D, Antonucci E, Ageno W, et al. The Predictive ability of bleeding risk stratification models in very old patients on vitamin K antagonist treatment for venous thromboembolism: results of the prospective collaborative EPICA study. J Thromb Haemost 2013; 11: 1053-8

Page 29: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Is the benefit associated with antithrombotic therapy greater than the risk?

Page 30: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Anticoagulant Therapy in Elderly

Patti G, Lucerna M, De Caterina R, et al. Thromboembolic Risk, Bleeding Outcomes and Effect of Different Antithrombotic Strategies in Very Elderly Patients with Atrial Fibrillation: A Sub- Analysis from the PREFER in AF. Heart Assoc. 2017, e005657. DOI: 10.1161/JAHA.117.005657

Page 31: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Anticoagulant Therapy in Elderly

Patti G, Lucerna M, De Caterina R, et al. Thromboembolic Risk, Bleeding Outcomes and Effect of Different Antithrombotic Strategies in Very Elderly Patients with Atrial Fibrillation: A Sub- Analysis from the PREFER in AF. Heart Assoc. 2017, e005657. DOI: 10.1161/JAHA.117.005657

Page 32: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Anticoagulant Therapy in Elderly

Patti G, Lucerna M, De Caterina R, et al. Thromboembolic Risk, Bleeding Outcomes and Effect of Different Antithrombotic Strategies in Very Elderly Patients with Atrial Fibrillation: A Sub- Analysis from the PREFER in AF. Heart Assoc. 2017, e005657. DOI: 10.1161/JAHA.117.005657

Page 33: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Birmingham Atrial Fibrillation Treatment of the Aged Study

(BAFTA)• Warfarin (n= 488) vs. Aspirin (n=485) in ≥75

years of age • Prospective Randomized open-label trial • Primary Aim:

– Fatal and non-fatal stroke– Intracranial hemorrhage– Other clinically significant arterial embolism

Mant J, Hobbs FD, Murray E. et al. Warfarin vs aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham atrial fibrillation treatment of the

aged study, BAFTA): a randomized controlled trial. Lancet 2007; 370: 493-503.

Page 34: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Warfarin vs. Aspirin

Mant J, Hobbs FD, Murray E. et al. Warfarin vs aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham atrial fibrillation treatment of the

aged study, BAFTA): a randomized controlled trial. Lancet 2007; 370: 493-503.

Page 35: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Warfarin vs. Aspirin

Mant J, Hobbs FD, Murray E. et al. Warfarin vs aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham atrial fibrillation treatment of the aged study, BAFTA): a randomized controlled trial. Lancet 2007; 370: 493-503.

Page 36: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

WHICH ANTICOAGULANT

WOULD YOU CHOOSE?

Page 37: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Bleeding-Related Readmissions● Very little evidence in the elderly population● Overall major bleeding seems to be equal with

DOACs vs. warfarin

● DOACs are associated with lower readmissions due to ICH but increased readmissions due to GI bleed

Page 38: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

DOAC: Concerns in Elderly• Lower body mass index (BMI 18.3)• Altered body composition• Higher frequency of renal

impairment (CKD3)

• (James also has anemia and increased Falls risk)

= inconsistent levels of anticoagulation?

Page 39: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Stroke and Systemic Embolism in Population

(< 75)

DOAC vs.

Warfarin

M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: Systematic review and meta-analysis. Circulation. 2015; CIRCULATIONAHA.114.013267, originally published May 20,2015

Page 40: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Stroke and Systemic Embolism in Population

(≥ 75)

DOAC vs.

Warfarin

M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: Systematic review and meta-analysis. Circulation. 2015; CIRCULATIONAHA.114.013267, originally published May 20,2015

Page 41: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Major Bleeding in Total Population

DOAC vs.

Warfarin

M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: Systematic review and meta-analysis. Circulation. 2015; CIRCULATIONAHA.114.013267, originally published May 20,2015

Page 42: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Major Bleeding in Elderly (≥ 75)

DOAC vs.

Warfarin

M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: Systematic review and meta-analysis. Circulation. 2015; CIRCULATIONAHA.114.013267, originally published May 20,2015

Page 43: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

DOAC vs. Warfarin

All Cause Deathin Population

(<75)

M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: Systematic review and meta-analysis. Circulation. 2015; CIRCULATIONAHA.114.013267, originally published May 20,2015

Page 44: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

DOAC vs. Warfarin

All Cause Deathin Elderly

(≥ 75)

M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: Systematic review and meta-analysis. Circulation. 2015; CIRCULATIONAHA.114.013267, originally published May 20,2015

Page 45: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Major Bleeding and Renal Function

Geldof V, Vadenbiele C, Vanassche T, et al. Venous thromoboembolism in the elderly: efficacy and safety of non-VKA oral anticoagulants. Thrombosis Journal 2014 (12): 21

Page 46: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

NOW WHICH ANTICOAGULANT

WOULD YOU CHOOSE ?

Page 47: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Better care, better population health and lower costs through improvement.

Questions?

Page 48: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

When deciding to use a DOAC in the elderly, which factor(s)

should be considered?

A. Renal impairmentB. Low body mass indexC. Fall riskD. All of the above

Page 49: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

Apixaban may be favorable in the elderly due to less major

bleeding compared to the other oral anticoagulants.

A. True B. False

Page 50: Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies, et al. Efficacy and harms of direct oral anticoagulants in elderly for stroke prevention

If deciding to start a DOAC in a patient with renal

insufficiency, rivaroxaban may be safer compared to the

other DOACs.A. True B. False