Management Issues in the Elderly

From the 10th Annual Norman N. Krieger, MD, Lecture in Geriatric Medicine,Wayne State University School of Medicine, Detroit, MI

Educational Objectives

The goals of this program are to improve the management of anticoagulation therapy and abdominal aortic aneurysms in the elderly. After hearing and assimilating this program, the clinician will be better able to:

1.   Discuss the reasons behind the current underutilization of warfarin for anticoagulation therapy.

2.   Cite current American College of Chest Physician guidelines for anticoagulation in elderly patients.

3.   Recommend appropriate periprocedural management for an elderly patient on oral anticoagulant therapy.

4.   Describe the epidemiology and predisposing risk factors for abdominal aortic aneurysms.

5.   Effectively screen patients for aneurysms.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Garwood has served as a consultant for Blue Cross Blue Shield of Michigan. Dr. Rubin and the plan­ning committee reported nothing to disclose. In her lecture, Dr. Garwood presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Drs. Garwood and Rubin spoke at the 10th Annual Norman N. Krieger, MD Lecture in Geriatric Medicine, held No­vember 4, 2009, in Detroit, MI and sponsored by the Wayne State University School of Medicine. The Audio-Digest Foundation thanks the speakers and the Wayne State University School of Medicine for their cooperation in the pro­duction of this program.

Anticoagulation in the Elderly

Candice Garwood, PharmD, Clinical Assistant Professor, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, and Clinical Pharmacy Specialist, Harper University Hospital, Detroit, MI

Introductory remarks: atrial fibrillation (AF), venous thromboembolism (VTE), and mechanical heart valve re­placement most common indications for use of warfarin; warfarin underutilized (according to current American College of Chest Physicians [ACCP] guidelines, only »50% of patients eligible for drug actually receive it); rea­sons for warfarin underutilization  —benefits often underestimated; adverse effects overestimated; patient age; pa­tient understanding of therapy; risk for falls

Warfarin vs aspirin in management of AF: AF Investigators (AFI) trial  —  analyzed data from 5 recent randomized trials; results showed »68% relative risk reduction (RRR) for stroke with warfarin vs »21% with aspirin; Birming­ham Atrial Fibrillation Treatment of the Aged (BAFTA) trial  —  >900 outpatients ³75 yr of age randomized to war­farin (with target international normalized ratio [INR] of 2-3) or low-dose aspirin; those on warfarin had significant RRR for combined end point of stroke, intracranial hemorrhage (ICH), and systemic embolus

Bleeding associated with warfarin: bleeding while on warfarin generally related to other underlying cause (eg, co­lon polyps); controversial whether increased risk for bleeding associated with advanced age; ICH more frequent in elderly patients (may be due to hypertension or to intensity of anticoagulation); trial data show that as intensity of anticoagulation increases (especially at INR >5), risk for hemorrhagic stroke increases exponentially; factors con­tributing to bleeding  — start of warfarin therapy; quality of management (dosing; monitoring; time in therapeutic range [TTR]); hypertension; data show risk for adverse bleeding event much higher during first month on warfarin than during remainder of therapy

Establishing warfarin dose: factors that influence appropriate dose include interactions with other medications, eg, amiodarone; comorbidities; body surface area (larger patients often require higher dose); sex (men often require higher dose than women); ethnicity (blacks often require higher dose, and Asians lower dose, than white patients); genetics; age (studies show that maintenance dose of warfarin decreases by 8% per decade); warfarin dose in elderly  —  ACCP guidelines and American Geriatrics Society suggest starting dose of £5 mg may be appropriate in elderly patients and those at high risk for bleeding (other than blacks); physicians advised to monitor patients closely to ensure appropriate dose

Frequency of monitoring: at initiation of warfarin therapy  —  if inpatient, monitor daily (once therapeutic range reached, decrease to every 2 days); if outpatient, monitor every few days; during maintenance therapy  —  monitoring interval of £4 wk recommended (more frequent monitoring advised for elderly patients)

Adjustment of warfarin dose: in patients with INR just outside therapeutic range (TR), adjust dose in increments of 5% to 20%, based on cumulative weekly dose (another option is more frequent monitoring); speaker increases dose in increments of 5% to 10%, and uses monitoring as basis of next dose adjustment

Time in therapeutic range (TTR): longer TTR correlates with decreased risk for bleeding events; studies also show that patients whose INR remains outside of TR for significant periods have most bleeding events

Older age as predictor of stable INR control: recent study found that age >70 yr predicted stable INR (defined as 100% TTR over 6-mo period) during chronic anticoagulation therapy

Patient education: in another recent study, elderly patients started on warfarin asked to rate education they received about their anticoagulation therapy; results showed patients who rated education satisfactory had longest TTR and fewest major bleeding events; those patients who rated their education as insufficient had highest rate of bleeding

Hypertension increases risk for bleeding in patients taking warfarin: hypertension often present in geriatric pa­tients and highly correlated with risk for ICH (risk exacerbated by anticoagulation therapy); data from Perindopril Protection Against Recurrent Stroke Study (PROGRESS) showed that even modest reduction in systolic blood pressure (BP) dramatically reduces risk for ICH

Risk for falls: each year, »33% of community-dwelling seniors fall; »10% of falls result in serious injury; »2% to 10% of falls that cause injury result in head trauma; »50% of subdural hematomas secondary to head trauma; study on falls and subdural hematoma in patients with AF  —  found that in patients at low, moderate, or high risk for stroke, quality-adjusted life years (QUALY) resulting from warfarin therapy outweighed QUALY resulting from aspirin or no treatment; authors concluded that patient with average risk of stroke from AF must fall »300 times/yr for risk associated with anticoagulation therapy to outweigh its benefits; risk for falls alone should not determine whether patient should be placed on anticoagulation therapy

Perioperative management of patients on warfarin: bridging patients on anticoagulation therapy necessary be­cause warfarin has highly variable duration of action (overall duration 2-5 days); ACCP guidelines recommend stopping warfarin »5 days before surgery to minimize bleeding due to residual effects of anticoagulant; periopera­tive management of anticoagulation “balancing act” (must weigh patient risk factors for bleeding and thrombosis vs surgical risk factors to properly risk stratify patient)

Perioperative statistics: RRR for thromboembolism produced by oral anticoagulation therapy varies (65%-80%) with indication for warfarin; arterial thromboembolism fatal in »15% of patients with mechanical heart valves and causes death or disability in »70% of all patients; VTE causes death and disability in »5% of patients; major post­operative bleeding fatal in »3% of patients

Surgeries and risk for bleeding: procedures associated with high risk for bleeding include open heart surgery, major abdominal surgery, urologic procedures, polypectomy, and surgeries lasting >45 min; those with low risk include laparoscopic surgeries with small incisions, superficial dermatologic procedures, and biopsies

Risk categories for thromboembolism: based on patient’s annual risk without anticoagulants; low risk categorized as <4%, moderate risk, 4% to 10%, and high risk, ³10%

CHADS2 score: system for estimating risk for stroke in patients with AF; patients assigned 1 pt for each common risk factor (congestive heart failure; hypertension; age ³75 yr; diabetes), and 2 points for history of previous stroke or transient ischemic attack (TIA); score of 0 to 1 indicates low risk, 5 to 6 indicates high risk

Indicators of risk for VTE: high risk  —  history of VTE within past 3 mo or severe thrombophilia; moderate risk  —  history of VTE within past year but not past 3 mo, nonsevere thrombophilia, recurrent VTE or active cancer treated within past 6 mo; low risk  —  history of VTE >12 mo ago

Risk for VTE in patients with mechanical heart valves: high risk  —  those with mitral valve replacement, older valves (eg, caged ball, disk), or stroke or TIA within past 6 mo; moderate risk  —  those with bileaflet aortic valve re­placement (AVR) plus AF or any other stroke risk factors; low risk  —  patients with bileaflet AVR without AF or stroke risk factors

ACCP guidelines for bridging strategy based on VTE risk: patients at low risk  —  consider no parenteral anticoag­ulant coverage or low dose of low-molecular-weight heparin (LMWH); patients at medium risk  —  low or full dose of parenteral anticoagulant; patients at high risk  —  full dose of parenteral anticoagulant

Comments: ACCP guidelines advise against use of bridging strategy and suggest that warfarin and aspirin can be continued during selected dental procedures (single or multiple tooth extractions; root canal; crown and bridge pro­cedures; administer prohemostatic agent, eg, Surgicel), cataract surgery (low risk for major bleeding because cata­ract typically located in avascular area of eye), and dermatologic procedures (if minor, such as excision of basal cell or squamous cell carcinoma or mole)

Antiplatelet agents (APs): discontinue 7 to 10 days before surgery and restart within 24 hr after surgery; continue aspirin through surgery in patients with high cardiac risk, those undergoing coronary artery bypass graft or percuta­neous coronary intervention (PCI), and those with stent; continue clopidogrel during or immediately after PCI, or if patient has had bare metal stent placed within 6 wk or drug-eluting stent within 12 mo

Heparin: use largely replaced by LMWH (can be used in outpatient therapy); 3 forms of LMWH available; enoxapa­rin most commonly used for perioperative anticoagulation; used in treatment and in low prophylactic doses; must adjust dose in patients with poor kidney function

Fondaparinux: available in treatment and prophylactic doses; dose based on weight; contraindicated in patients with creatinine clearance <30 mL/min; half-life »20 hr (longer in elderly population); not included as option in ACCP guidelines, but sometimes used in periprocedural management; appropriate for patients with history of heparin-in­duced thrombocytopenia; per Food and Drug Administration, indicated for treatment and prevention of VTE; no data on use in patients with AF or mechanical heart valves

Approach to outpatient periprocedural bridging: stop AP therapy »7 days before, and stop warfarin and begin LMWH »5 days before procedure; last dose of LMWH should be »50% of total daily dose, given »24 hr before procedure; resume warfarin and AP agent »12 to 24 hr after surgery (depending on hemostasis and patient’s risk for bleeding); resume LMWH 24 hr after most surgeries (delay until 2-3 days postsurgery if procedure has high risk of bleeding); continue LMWH and warfarin until INR therapeutic; cost also factor that should be considered when de­ciding whether appropriate to bridge patient

Aortic Aneurysms of the Abdomen

Jeffrey Rubin, MD, Professor and Chief of Vascular Surgery, Wayne State University School of Medicine, and Harper University Hospital, Detroit, MI

Aneurysms: can affect any artery; most common site abdominal aorta (second most common site thoracic aorta, fol­lowed by femoral, popliteal, and upper extremity arteries); »95% of abdominal aortic aneurysms (AAA) located below renal arteries (»5% in perirenal area); by definition, »1.5 times size of normal aorta; 3 types (fusiform [most common]; saccular [commonly found in past in patients with tertiary syphilis]; dissection [does not involve all lay­ers of artery]); aneurysmal sac contains large amount of organized thrombus; blood flow goes through center of lu­men, so aneurysms often undetectable on standard arteriography; may also contain blood clot and other materials (associated with risk for embolic phenomena as well as rupture)

Treatment: current treatment aneurysmorrhaphy (open operation to replace aorta with graft); endovascular repair newest modality (minimally invasive)

Epidemiology: »100,000 aneurysms diagnosed and »15,000 deaths from undiagnosed aneurysms in United States each year; infrarenal aneurysms »4 times more common in men than in women; higher mortality rate in women; occur mainly in elderly (average age »72 yr); rupture rates decreasing (particularly in men) because of new screening programs; most aneurysms asymptomatic and discovered incidentally during imaging for another con­dition; 33% rupture (>50% of these patients die before they get to hospital and »90% die in hospital)

Predisposing factors: familial aneurysm disorder; recommended that immediate family members of patient diag­nosed with aneurysm be screened with ultrasonography (US; 20%-25% chance they will also have condition); genetic diseases, eg, Marfan syndrome, Ehlers-Danlos syndrome; age (average age 72 yr); male sex; cigarette smoking; arteriosclerosis; hypertension; hypercholesterolemia; aneurysms found less often in black and Asian populations, and in individuals with diabetes

Signs and symptoms: identifying aneurysm on physical examination (PE) difficult; symptoms in patient who pres­ents with ruptured aneurysm classic (ripping and tearing sensation in abdomen that extends to back); once hema­toma forms, it can cause retroperitoneal irritation, leading to pain that extends into groin, testicles, or buttocks

Comorbidities: coronary artery disease in >50% of cases; chronic obstructive pulmonary disease (COPD) in »30% of cases; history of asthma has higher association with aneurysms

Detection on PE: only »33% of aneurysms palpable (can usually be felt in epigastrium); deep manipulation (looking for tenderness) not recommended; aneurysms of iliac artery “silent killers” (cannot be felt on PE and difficult to de­tect); popliteal and femoral artery aneurysms rare but frequently bilateral, and patient likely to also have aortic an­eurysm

Screening for aneurysms: indications  —  pulsatile abdominal mass; peripheral thoracic aneurysms; high-risk patients  —  male smokers >65 yr of age and female smokers >70 yr of age; anyone >55 yr of age with family history of aneurysm; least expensive and best screening test is US; Medicare allows for one-time US screening for “quali­fied seniors”; benefits of screening  —  significant reduction in risk for ruptured aneurysms reported in men 65 to 75 yr of age; reduction of patient mortality through early identification and repair; recommended screening frequency  —  aneurysms <3 cm generally do not need to be followed; however, if patient ³55 yr of age and has fam­ily history of aneurysm, speaker recommends repeat US within »3 yr to check for growth; aneurysms »3 to 4 cm should be followed every 12 mo; aneurysms >4 cm must be screened every 6 mo or addressed by surgeon; com­puted tomography required when evaluating patients for intervention; goal to make diagnosis early and determine most effective and timely treatment

Factors associated with increased risk of rupturing: smoking; female sex; hypertension; COPD; childhood history of asthma; size most important risk factor (larger the aneurysm, greater the risk of rupture within year); average growth rate 3 to 4 mm/yr (if growth more rapid, early and aggressive treatment recommended)

Comments: repair of aneurysms <1.5 times size of normal aorta cannot be justified because risk associated with re­pair greater than risk for rupture; study data do not support repair of aneurysms £3.5 cm

Guidelines for treatment: depends on patient, risk factors, size of aneurysm, and life expectancy; female sex most important variable associated with rupture of small aneurysms (rupture of aneurysms in women occurs earlier and at smaller diameter than in men)

Suggested Reading

Ansell J et al: Pharmacology and management of the vitamin Kantagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133(6 Suppl):160S, 2008; Chaikof EL: Caring for patients with an abdominal aortic aneurysm: data, knowledge, and wisdom. J Vasc Surg 50(4 Suppl):S1, 2009; Chaikof EL et al: SVS practice guidelines for the care of patients with an abdominal aortic aneurysm: executive summary. J Vasc Surg 50(4):880, 2009; Dinwoodey DL, Ansell JE: Hepa­rins, low-molecular-weight heparins, and pentasaccharides: use in the older patient. Cardiol Clin 26(2):145, 2008; Douketis JD et al: The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133(6 Suppl):299S, 2008; Ezekowitz MD, Falk RH: The increasing need for anticoagulant therapy to prevent stroke in patients with atrial fibrillation. Mayo Clin Proc 79(7):904, 2004; Garwood CL, Corbett TL: Use of anticoagula­tion in elderly patients with atrial fibrillation who are at risk for falls. Ann Pharmacother 42(4):523, 2008; Ginter JF, Linzmeyer J: Abdominal aortic aneurysm repair: matching patients with approaches. JAAPA 22(7):26, 2009; Man-Son-Hing M et al: Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 159(7):677, 1999; Mant J 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 370(9586):493, 2007; No authors listed: PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individu­als with previous stroke or transient ischaemic attack. Lancet 358(9287):1033, 2001; No authors listed: Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 154(13):1449, 1994; Paraskevas KI: The size threshold for elective abdominal aortic aneurysm repair may need to be lowered in the endovascular era. J Endovasc Ther 16(4):524, 2009; Spyropoulos AC et al: Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry. J Thromb Haemost 4(6):1246, 2006; Symons N, Gibbs R: The management of abdominal aortic aneurysms. Br J Hosp Med (Lond) 70(10):566, 2009; Witt DM et al: Outcomes and predictors of very stable INR control during chronic anticoagulation therapy. Blood 114(5):952, 2009.