Use of Anticoagulants in Geriatrics: Current Evidence and ... · M Sharma, VR Cornelius, JG Davies,...

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

Collaboration

JABSOM • – Geriatric Workforce Enhancement Program

Mountain• -Pacific Quality Health

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

1.0 AMA PRA Category 1 Credits™

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 cbarton@mpqhf.org

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.

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

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

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)

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.

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

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

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.

WHAT IS JAMES’ RISK OF STROKE?

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

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

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)

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

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

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

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

Mechanism of Action

Timeline of FDA-Approvals

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

Bleeding-Related Readmissions

WHAT IS JAMES’ RISK OF

BLEEDING?

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

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

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

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

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

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

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

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

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

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.

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.

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.

WHICH ANTICOAGULANT

WOULD YOU CHOOSE?

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

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?

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

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

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

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

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

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

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

NOW WHICH ANTICOAGULANT

WOULD YOU CHOOSE ?

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

Questions?

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

Apixaban may be favorable in the elderly due to less major

bleeding compared to the other oral anticoagulants.

A. True B. False

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