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 Better care, better population health and lower costs through improvement.
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.
Use of Anticoagulants in Geriatrics: Learning Objectives and Case Study Aida Wen, MD Associate Professor, Department of Geriatric Medicine The John A Burns School of Medicine Better care, better population health and lower costs through improvement.
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 CHF Past Medical History: HTN GERD Arthritis Anemia Chronic Kidney Disease (Stage 3)
Vitals: Patient Case: James BP: 160/90, P: 90 bpm (Irregular), O 2 Sat: 92% RA Wt : 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.
Medications: Patient Case: James 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?
Use of Anticoagulants in Geriatrics: Current Evidence and Special Considerations Aryn You, PharmD Assistant Professor, Pharmacy Practice The Daniel K. Inouye College of Pharmacy Better care, better population health and lower costs through improvement.
CHA 2 DS 2 -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 9 th Edition (2012) Patients with CHA 2 DS 2 -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 Anticoagulants Warfarin (Coumadin, Jantoven ) NOAC = DOAC Novel Oral Anticoagulants = Direct Oral Anticoagulants Dabigatran (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-BLED Hypertension (1 point) Renal Disease (1 point) Liver Disease Stroke History Prior major bleeding or predisposition to bleeding 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 (1 point)
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) = inconsistent levels of anticoagulation? (James also has anemia and increased Falls risk)
DOAC vs. Warfarin Stroke and Systemic Embolism in 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 Stroke and Systemic Embolism in 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 Major Bleeding in Total Population 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 Major Bleeding in 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
DOAC vs. Warfarin All Cause Death in 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 Death in 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 impairment B. Low body mass index C. Fall risk D. 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