Thromboembolic prevention in elderly

Thromboembolic Prevention in Elderly Patients With Atrial Fibrillation

ByMohamed Attia, MD

Geriatric Medicine FellowGeorge Washington University Hospital

Learning Objectives

• Role of aspirin in elderly with non-valvular aFib • Risk of stroke in elderly with non-valvular aFib.• Risk factors in frail elderly patients with non-

valvular aFib• Identify circumstances under which you would

not recommend anticoagulants Rx in older adults with non-valvular aFib

75 yo M with Hx of syncope and non-valvular Afib. Medications include digoxin (BP 90/60) and Pradaxa BID. He is ADLs and IADLs independent. He c/o bruises due to frequent falls. Would you consider switching over to ASA?

• In the general population, ASA decreases risk of stroke by 22% vs Warfarin 64%

• Guidelines recommend the use of VKAs for thromboembolic prophylaxis but do not generally recommend the use of antiplatelets in patients aged ≥75 years.

- Hart RG, Pearce LA, Aguilar MI. Meta-analysis: Antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann InternMed 2007;146:857e867-HartRG,Pearce LA,AguilarMI.Adjusted-dose warfarin versus aspirin for preventing stroke in patients with atrial fibrillation. Ann Intern Med 2007;147:590e592-Singer DE, Chang Y, Fang MC, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009;151:297e305- You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic therapy and prevention of thrombosis, 9th ed: AmericanCollege of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e531See575S

Birmingham Atrial Fibrillation Treatment of the Aged trial demonstrated the superior efficacy of warfarin in stroke prevention in the elderly, when compared to aspirin

973 patients aged ≥75 years (mean age 81.5 years, SD 4·2) with atrial fibrillation were recruited from primary care and randomly assigned to warfarin (target INR 2–3) or ASA (75 mg per day). Follow-up was for a mean of 2.7 years

- Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): A randomised controlled trial. Lancet 2007;370:493e503

Aspirin Warfarin

44 21 Stroke

1 2 IC

3 1 Systemic embolus

1.6% 1.4% ECH risk

- Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): A randomised controlled trial. Lancet 2007;370:493e503

Wilke T, Groth A, Mueller S, et al. Incidence and prevalence of atrial fibrillation: An analysis based on 8.3 million patients. Europace 2013;15:486e493.

• Atrial fibrillation (AF) is the most common serious arrhythmia

• In patients ≥75 years the incidence is around 26.3/1000 person-years, compared with 4.1/1000 person-years in the overall population

• The attributable risk of stroke increased with age, rising from 1.5% for those aged 50-59 years to 23.5% for those aged 80-89 years

• Increasing age is associated with stroke severity. In approximately 66% of patients ≥80 years, a stroke will result in death or disability

- Saposnik G, Black SE, Hakim A, et al. Age disparities in stroke quality of care and delivery of health services. Stroke 2009;40:3328e3335- Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke 1991;22:983e988.

Assess Thromboembolic Risk in AF

CHADS2• Congestive heart failure• Hypertension• Age 75,• Diabetes mellitus• Hx of Stroke or TIA

CHA2DS2-VASc• Congestive heart failure(+1)• Hypertension(+1)• Age 75(+2)• Diabetes mellitus(+1)• Hx of Stroke or TIA(+2)• Vascular disease(+1)• Age 65-74(+1)• Female Sex(+1)

Conditions that may interfere with long-term anticoagulation

1- Age2- Comorbidities3- Polypharmacy4- Adherence5- Cognitive Impairment6- Mobility and Monitoring Barrier7- Nutritional Status and Swallowing Disorders8- Risk of Falls9- Reduced Life Expectancy

Thromboembolic Prevention in Frail Elderly Patients With Atrial Fibrillation: A Practical Algorithm Serena Granziera MD, Alexander T. Cohen MD, Giovanni Nante MD, Enzo Manzato MD, PhD , Giuseppe Sergi MD, University of Padova, Department of Medicine- DIMED, Padova, Italy King’s College Hospital, London, United Kingdom Department of Thrombosis and Hemostasis, Guy’s and St Thomas’ Hospitals, London, United Kingdom, JAMDA 16 (2015) 358e364

Age

• Elderly Patients are more likely to present with other comorbidities in the CHADS score

- Camm AJ, Kirchhof P, Lip GYH, et al. European Heart Rhythm A, European Association for Cardio-Thoracic S.Guidelines for the management of atrial fibrillation: The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace 2010;12:1360e1420.- Fang MC, Chang Y, Hylek EM, et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med 2004;141:745e752

• Aging raises the risk of serious bleeding (2.5 times more common in people aged ≥85 years)

• Risk for intracerebral hemorrhage is not diminished in elderly patients with atrial fibrillation when anticoagulation is maintained below an INR of 2.0

• Increased age alone should not be considered a reason for holding antithrombotic therapy, unless the risk of bleeding is too high

HEMORR2HAGES Risk Factors (score)DefinitionHepatic (1) or renal disease (1): Hepatic disease: cirrhosis, two-fold or greater elevation of AST or APT, or albumin < 3.6 g/dL- Renal insufficiency: Cr clearance < 30 ml/minEthanol use (1): History of alcohol abuse, recent hospitalization for alcohol-related illness, and worsening liver diseaseMalignancy (1): Recent metastatic cancerOlder (age > 75) (1): Calculated from birth dateReduced platelet count (1) or function (1): Platelets < 75,000 , Schedule use of antiplatelet therapy (e.g. daily aspirin) or NSAID therapy; or blood dyscrasiaRe-Bleeding (2): Prior hospitalization bleedingHypertension, uncontrolled (1): Blood pressure not currently in control: most recent systolic bp > 160 torrAnemia (1): Most recent hematocrit < 30 or hemoglobin < 10 g/dLGenetic factors (1): CYP2C9*2 and/or CYP2C9*3Elevated risk of fall including neuropsychiatric disease (1): Alzheimer's dementia, Parkinson's disease, schizophrenia, or any condition predisposing to repeated fallsStroke (1): Prior ischemic stroke or brain infarct detected by brain imaging

Score of 0 or 1 were classified as low-risk, 2 or 3 intermediate-risk, ≥4 high-risk

http://www.warfarindosing.org/Source/PredictionRule.aspx

Comorbidities• Acute condition: need to decrease dose of VKAs• Chronic condition:- Renal Impairment [CrCl] <30 mL/minute Increases the risk of both bleeding and

thrombosis CrCl <15 mL/minute: All new oral anticoagulants are

contraindicated (<30 mL/minute for dabigatran) and VKA therapy is recommended

CrCl 15- 30 mL/minute: the dose should be reduced

- Marinigh R, Lane DA, Lip GY. Severe renal impairment and stroke prevention in atrial fibrillation: Implications for thromboprophylaxis and bleeding risk. J Am Coll Cardiol 2011;57:1339e1348.- Harel Z, Sholzberg M, Shah PS, et al. Comparisons between novel oral anticoagulants and vitamin K antagonists in patients with CKD. JASN 2014;25: 431e442.

Liver impairment:• Severe and moderate liver impairment (Child Pugh class B-C) is a contraindication for both VKAs and NOACs.

Turpie AG, Kreutz R, Llau J, et al. Management consensus guidance for the use of rivaroxabandAn oral, direct factor Xa inhibitor. Thromb Haemost 2012;108: 876e886.

Polypharmacy Drug-drug interaction Risk factor for poor compliance Frequent changes to the medication regimen

- Froom P, Miron E, Barak M. Oral anticoagulants in the elderly. Br J Haematol 2003;120:526e528.- Barat I, Andreasen F, Damsgaard EM. Drug therapy in the elderly: What doctors believe and patients actually do. Br J Clin Pharmacol 2001;51:615e622.

Polypharmacy

POLYPHARMACY CONCERNS IN THE GERIATRIC POPULATION RONNA D. COMPTON, DO ASSISTANT PROFESSOR FAMILY & GERIATRIC MEDICINE UNIVERSITY OF LOUISVILLE VCOM CLASS OF 2007

ExamplesMedications interfere with VKA

dose response Amiodarone, Antibiotics such as quinolones

and macrolides, Antifungal agents, Nonsteroidal anti-

inflammatory drugs, Selective serotonin reuptake

inhibitors, Omeprazole, and Lipid-lowering agents

Medications interfere with NOACs dose response

• Verapamil,• Amiodarone, • Rifampicin, • Antiretroviral

cytochrome P450 3A4 inhibitors

- Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e152See184S.

• Prioritize the disease for treatment• NOACs are less prone to D-D interaction

compared with VKAs

Recommendations


Adherence

Estimates of non-adherence in elderly patients with chronic conditions such as AF vary from 40% to 75%

Reasons for poor adherence in the elderly: Lack of support (eg, caregiver) Lack of disease knowledge Physical difficulties associated with taking medicines Polypharmacy Cost

- Doggrell SA. Adherence to medicines in the older-aged with chronic conditions: Does intervention by an allied health professional help? Drugs Aging 2010;27:239e254.- Cohen AT, Maillardet L, Yavin Y. Will a once-weekly anticoagulant for the treatment and secondary prevention of thromboembolism improve adherence? Thromb Haemost 2009;101:422e427

Adherence• Poor adherence Oral anticoagulants are not Recommended• Suboptimal VKAs are safer (Short half life & Close monitoring)

If physician decides to prescribe NOACs, he should schedule frequent visits and telephone calls

- Waterman AD, Milligan PE, Bayer L, et al. Effect of warfarin nonadherence on control of the International Normalized Ratio. AJHP 2004;61:1258e1264.- Pengo V, Crippa L, Falanga A, et al. Questions and answers on the use of dabigatran and perspectives on the use of other new oral anticoagulants in patients with atrial fibrillation. A consensus document of the Italian Federation of Thrombosis Centers (FCSA). Thromb Haemost 2011;106:868e876

Cognitive Impairment• Cognitive impairment is prevalent among the elderly, affecting

approximately 30% of subjects between 80 and 89 years old.

• It has been studied in different trials, with different results - Kagansky et al and Khreizat et al showed that cognitive variables were not associated with an increased rate of bleeding - Van Deelen et al found that in elderly people with AF, an MMSE score <23 was independently associated with inadequate INR control

- Plassman BL, Langa KM, Fisher GG, et al. Prevalence of dementia in the United States: The aging, demographics, and memory study. Neuroepidemiolog 2007;29:125e132.- Kagansky N, Knobler H, Rimon E, et al. Safety of anticoagulation therapy in well-informed older patients. Arch Intern Med 2004;164:2044e2050.- Khreizat HS, Whittaker P, Curtis KD, et al. The effect of cognitive impairment in the elderly on the initial and long-term stability of warfarin therapy. Drugs Aging 2012;29:307e317.- van Deelen BA, van den Bemt PM, Egberts TC, et al. Cognitive impairment as determinant for sub-optimal control of oral anticoagulation treatment in elderly patients with atrial fibrillation. Drugs Aging 2005; 22:353e360

Cognitive Impairment Clinicians should ensure that a caregiver monitors drug intake.

In those with poor adherence and poor supervision, withholding oral anticoagulation should be considered.


Mobility and Monitoring Barriers INR monitoring requires visits for phlebotomy

at home or patient transport to the anticoagulation clinic, and this is both time consuming and expensive.

NOACs may be preferred instead of VKAs in patients with decreased mobility


Nutritional Status and Swallowing Disorders

Elderly are commonly characterized by low weight and/or low BMI

Anorexia due to Polypharmacy and polymorbidity low food intake e.g. poor economic and social support

These patients may benefit from the use of NOACs, because, the effects of direct inhibitors are not known to vary with changes in dietThromboembolic Prevention in Frail Elderly Patients With Atrial Fibrillation: A Practical Algorithm Serena Granziera MD, Alexander T. Cohen MD, Giovanni Nante MD, Enzo Manzato MD, PhD , Giuseppe Sergi MD, University of Padova, Department of Medicine- DIMED, Padova, Italy King’s College Hospital, London, United Kingdom Department of Thrombosis and Hemostasis, Guy’s and St Thomas’ Hospitals, London, United Kingdom, JAMDA 16 (2015) 358e364

Risk of Falls• Perceived as one of the main risk factors for

withholding anticoagulation

• Person on Warfarin must fall almost daily to outweigh the benefit of anticoagulation

- Gage BF, Birman-Deych E, Kerzner R, et al. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med 2005; 118:612e617.-Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999;159:677e685-The Decision to Anticoagulate: Assessing whether Benefits Outweigh the Risks for Patients with Atrial Fibrillation GENOMERLI, M.D., AND HOWARD H. WEITZ, M.D. Division of Internal Medicine and Cardiology, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA . Clin. Cardiol. 27, 313–320 (2004)

Reduced life expectancy There are no studies on AF thromboembolic prevention in such patients. Some data on anticoagulation in patients with malignancy,

VKA treatment in active cancer patients in other settings such as DVT yields suboptimal results

Definitive conclusions on the use of oral anticoagulation therapy in patients with reduced life expectancy cannot be drawn.

-Akl EA, Rohilla S, Barba M, et al. Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer: A systematic review. Cancer 2008;113:1685e1694-- Thromboembolic Prevention in Frail Elderly Patients With Atrial Fibrillation: A Practical Algorithm Serena Granziera MD, Alexander T. Cohen MD, Giovanni Nante MD, Enzo Manzato MD, PhD , Giuseppe Sergi MD, University of Padova, Department of Medicine- DIMED, Padova, Italy King’s College Hospital, London, United Kingdom Department of Thrombosis and Hemostasis, Guy’s and St Thomas’ Hospitals, London, United Kingdom, JAMDA 16 (2015) 358e364

Reduced life expectancy

It may be reasonable to withhold oral anticoagulation when life expectancy is less than 6 months:

1- It’s unlikely to improve all cause mortality or reduce admission and disability rate.

2- Other comorbidities make it difficult to control INR which can lead to high risk of bleeding


Conditions interfering with long-termanticoagulation

1- Age2- Comorbidities3- Polypharmacy4- Adherence5- Cognitive Impairment6- Mobility and Monitoring Barrier7- Nutritional Status and Swallowing Disorders8- Risk of Falls9- Reduced Life Expectancy


Decision making algorithm for the use of oral anticoagulants in patients with atrial fibrillation (<75 vs 75 years). CIRS, Cumulative Illness Rating Scale; Child Pugh class for liver disease; Mini-Nutritional Assessment; SPMSQ, Short Portable Mental Status Questionnaire; MPI, Multidimensional prognostic index


Favor VKAs

Favor NOACs

Severe Renal/ Liver impairment

Polypharmacy

Adherence

Nutritional Factors

Mobility

Cognitive Impairment

Risk of Fall

Other Comorbidities


Thank You

Thromboembolic prevention in elderly

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