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Anticoagulation in older adults

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Anticoagulation in older adults
Author
Gregory YH Lip, MD, FRCPE, FESC, FACC
Section Editors
Lawrence LK Leung, MD
Kenneth E Schmader, MD
Deputy Editor
Stephen A Landaw, MD, PhD
Last literature review version 19.3: Fri Sep 30 00:00:00 GMT 2011 | This topic last updated: Wed Oct 19 00:00:00 GMT 2011 (More)

INTRODUCTION — Most of the common cardiovascular disorders in older adults have a relationship to thrombosis, including ischemic heart disease, atrial fibrillation, valvular disease, and atherosclerotic vascular disease. Many of these patients require antithrombotic therapy, which raises questions regarding the appropriate use and safety of these agents, especially since older adults are at greater risk of anticoagulant-associated bleeding. The presence of concomitant physical and medical problems and the use of other drugs, especially the antiplatelet agents, increase the interactions and risks associated with anticoagulant therapy, requiring an assessment of the overall risk-benefit ratio [1].

Oral anticoagulation is commonly indicated in the following cardiovascular conditions:

 

  • Nonvalvular atrial fibrillation (see “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”)
  • Cardioembolic stroke (see “Secondary prevention for specific causes of ischemic stroke and transient ischemic attack”)
  • Valvular heart disease and prosthetic heart valves (see “Antithrombotic therapy in patients with prosthetic heart valves”)
  • Ischemic heart disease (see “Overview of the acute management of acute ST elevation myocardial infarction” and “Overview of the acute management of unstable angina and acute non-ST elevation myocardial infarction”)
  • Left ventricular dysfunction (see “Indications for anticoagulation in heart failure”)
  • Venous thromboembolic disease, including pulmonary embolism and deep vein thrombosis (see “Anticoagulation in acute pulmonary embolism” and “Treatment of lower extremity deep vein thrombosis”)
  • Peripheral vascular disease (see “Medical management of claudication”, section on ‘Warfarin’)

 

Some of these conditions, such as atrial fibrillation, venous thromboembolism, and heart failure, are much more prevalent in the elderly. The risk of venous thromboembolism, for example, increases exponentially with advancing age, rising from an annual incidence of approximately 30/100,000 at age 40 years to 90/100,000 at age 60 years and 260/100,000 at age 80 years [2]. With respect to heart failure, the Framingham Heart Study found a prevalence of 2 per 1000 in men and 1 per 1000 in women for the age range 45 to 54 years, rising to 8 per 1000 for men and 7 per 1000 women between 65 and 74 years [3].

The main topic to be reviewed here will be practical issues associated with anticoagulation in the elderly. The role of anticoagulation in specific disorders is discussed in detail in the appropriate topic reviews, as noted above.

ANCILLARY INFORMATION — The decision as to whether or not to offer anticoagulation to a specific older adult can be complex. In addition to the risks of bleeding and thrombosis, which are discussed below, there are other issues which impact on this decision. These are discussed elsewhere in UpToDate, as follows:

 

  • Presence of cognitive impairment: (See “Evaluation of cognitive impairment and dementia”.)
  • Drug prescribing in the older adult: (See “Drug prescribing for older adults”.)
  • Outpatient monitoring of anticoagulation control: (See “Outpatient management of oral anticoagulation”.)
  • Warfarin dosing in the older adult: (See “Therapeutic use of warfarin”, section on ‘Initial dose’.)
  • Dosing of low molecular weight heparin in the older adult: (See “Therapeutic use of heparin and low molecular weight heparin”, section on ‘Special patient groups’.)
  • Clinical practice guidelines: A Clinical Practice Guideline is available concerning the use of oral anticoagulants in the elderly, issued by the American Geriatrics Society and abstracted from the 2000 ACCP guidelines for antithrombotic therapy for prevention and treatment of thrombosis [4,5]. These latter ACCP guidelines have since been updated in 2008 [6,7].

 

OVERVIEW

Clinician concerns — Physician surveys have consistently cited patient age as a deterrent to the use of warfarin in atrial fibrillation [8]. This is due in part to concerns about poor compliance, difficulty monitoring patients in remote areas, recurrent falls, cognitive impairment, history of gastrointestinal bleeding, hypertension, cerebral hemorrhage, a risk of interaction with multiple other drugs, and possibly because of a decreased rate of clearance of this medication or an increased warfarin-associated inhibition of vitamin K-dependent clotting factors with increasing age [9-12]. (See “Risk of intracerebral hemorrhage in patients treated with warfarin”, section on ‘High risk patients’.)

Although anticoagulation is of benefit for some groups of elderly patients, there are a number of important concerns about the use of anticoagulation therapy in the elderly patient, particularly an increased risk for bleeding. These factors were evaluated in a study of 323 patients ≥80 years of age who were discharged from a hospital setting with a recommendation for treatment with oral anticoagulants and then followed for a mean of 29 months [13]. The rate of major bleeding was 2.4 events per 1000 patient-months. On multivariate analysis, the following factors were associated with an increased risk of bleeding:

 

  • Insufficient education concerning oral anticoagulants (odds ratio [OR] 8.8, 95% CI 2.0-50)
  • More than seven regular medications (OR 6.1, 95% CI 1.2-42)
  • INR values >3.0 (OR 1.08, 95% CI 1.03-1.14)

 

To examine the relationships among age, anticoagulation intensity, and risk for intracranial hemorrhage (ICH), a case–control study was performed in 170 patients who developed ICH during warfarin therapy for atrial fibrillation and 1020 matched controls [14]. Case-patients were significantly older than controls (median age 78 versus 75 years) and had higher median INRs (2.7 versus 2.3). The risk for ICH increased at ≥85 years of age (adjusted OR 2.5, 95% CI 1.3-4.7; referent age: 70 to 74 years) and at an INR of 3.5 to 3.9 (OR 4.6; 95% CI 2.3-9.4; referent INR, 2.0-3.0). INRs <2.0 were not associated with lower risk for ICH compared with INRs between 2.0 and 3.0 (OR 1.3, 95% CI 0.8-2.2). (See “Risk of intracerebral hemorrhage in patients treated with warfarin”, section on ‘High risk patients’.)

Thus, management of anticoagulation via the use of a vitamin K antagonist should focus on maintaining the INR in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than targeting values below 2.0.

Effect of age — Age ≥75 is one of the risk factors for thromboembolism in patients with atrial fibrillation (AF) (table 1). As examples:

 

  • In a cohort study of patients with AF and a CHADS2 score = 1 (ie, so-called intermediate risk), those with age >75 as a single risk factor had threefold increased risk of stroke and mortality compared with those with hypertension alone as a single risk factor [15].
  • In a Danish nationwide cohort study, age ≥75 as a single risk factor carried the greatest risk of stroke and thromboembolism compared with other single risk factors (ie, diabetes, hypertension, heart failure, etc.) [16].
  • In a study of patients with non-valvular atrial fibrillation and no CHADS(2) risk factors, the stroke/thromboembolic rate per 100 person-years increased progressively with age, being 0.23, 2.05, and 3.99 for those aged <65, 65 to 74, and ≥75 years, respectively [17].

 

There had remained uncertainties concerning the risk-benefit ratio for the use of anticoagulation for AF in such patients, and some have recommend a lower target INR (1.8 to 2.5) than in younger patients (2.0 to 3.0). However, the risk of major bleeding at an INR <2.0 is not lower than that seen at INRs in the range of 2.0 to 3.0.

This issue was addressed in the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study, a randomized trial of warfarin (INR 2.0-3.0) versus aspirin (75 mg/day) in elderly patients (age ≥75 years) with AF when tested in a primary care setting [18,19]. In this trial, 973 patients (mean age 81) were followed for an average of 2.7 years, with a primary thrombotic event rate (ie, fatal or nonfatal disabling stroke or significant arterial embolism) of 1.8 percent/year in the warfarin arm, compared with 3.8 percent/year in the aspirin arm (hazard ratio 0.48; 95% CI 0.28-0.80), while the risks of major hemorrhage (intracerebral as well as at all sites) were similar in the two treatment arms.

Results of the BAFTA study, along with a meta-analysis of similar randomized trials, indicate a relative risk reduction in all strokes by adjusted-dose warfarin versus antiplatelet therapy of about 40 percent [20], and support a policy of anticoagulation for elderly subjects with AF unless there are clear contra-indications. (See “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”.)

In the small trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO trial), aspirin was associated with less adverse effects compared with warfarin, which also had numerically less thromboembolism [21].

An analysis from the Atrial Fibrillation Investigators found that increasing patient age increased the risk of ischemic stroke (adjusted hazard ratio per decade increase (AHR) 1.45; 95% CI 1.26-1.66), serious bleeding (AHR 1.61; 95% CI 1.47-1.77), and cardiovascular events (AHR 1.43; 95% CI 1.33-1.53) [22]. When compared with placebo, both oral anticoagulation (OAC) and antiplatelet therapy (APT) significantly reduced the risk of ischemic stroke (OAC, AHR 0.36; 95% CI 0.29-0.45; APT, AHR 0.81; 95% CI 0.72-0.90) and cardiovascular outcomes (OAC, AHR 0.59; 95% CI 0.52-0.66; APT, AHR 0.81; 95% CI 0.75-0.88), whereas OAC significantly increased the risk of serious bleeding (AHR 1.56; 95% CI 1.03-2.37). Importantly, when compared with placebo, the relative benefit of APT for preventing ischemic stroke decreased significantly as patients aged.

Overall net benefit of anticoagulation in the older adult — In most, but not all, studies, thromboembolic rates and bleeding rates were both noted to increase with increasing age, calling into question whether there is a net benefit to the older patient when anticoagulation is employed [22-24]. A number of studies that have evaluated this issue are described below.

The overall benefit to the elderly patient from anticoagulation was addressed in a review of 4202 patients from the Leiden Anticoagulation Clinic treated because of mechanical heart valve prostheses, atrial fibrillation, or myocardial infarction [23]. The incidence rate (events per 100 patient-years) for thromboembolism in these adequately anticoagulated patients rose with increasing age, as follows:

 

  • Age <60 — 1.0 (adjusted (a)HR 1.0, reference group)
  • Age 60 to 70 — 1.4 (aHR 1.3, 95% CI 0.7-2.5)
  • Age 71 to 80 — 1.6 (aHR 1.7, 95% CI 1.0-3.1)
  • Age >80 — 2.4 (aHR 2.7, 95% CI 1.4-5.2)

 

Similarly, the incidence rate for hemorrhage increased with increasing age and was 50 to 75 percent higher than the risk for thromboembolism within each of the four age groups, as follows:

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  • Age <60 — 1.5 (aHR 1.0, reference group)
  • Age 60 to 70 — 2.1 (aHR 1.3, 95% CI 0.8-2.1)
  • Age 71 to 80 — 2.5 (aHR 1.7, 95% CI 1.0-2.5)
  • Age >80 — 4.2 (aHR 2.9, 95% CI 1.7-4.8)

 

Results from a large Swedish study found a significantly increased risk for major bleeding with advancing age in anticoagulated patients, although they did not find a correlation between increasing age and thromboembolic events [24].

An analysis of the Atrial Fibrillation Investigators database included observations in 8932 patients from 12 trials [22]. Patient age increased the risk of ischemic stroke (adjusted HR per decade increase 1.45; 95% CI 1.26-1.66) as well as the risk of serious bleeding (adjusted HR/decade 1.61; 95% CI 1.47-1.77). When compared with placebo, the absolute benefit of antiplatelet therapy appeared to decrease with increasing age, whereas the absolute benefit of oral anticoagulation therapy increased with increasing age.

Risk of falling — The risk of falling and developing traumatic intracranial hemorrhage is an important concern in elderly patients taking long-term anticoagulation. This subject is discussed separately. (See “Risk of intracerebral hemorrhage in patients treated with warfarin”, section on ‘Falls’.)

RISK OF STROKE — For the elderly with atrial fibrillation, the choice of optimal therapy to prevent stroke primarily depends upon the baseline risk of stroke. This subject is discussed in extensive detail separately. (See “Risk of embolization in atrial fibrillation” and “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”, section on ‘Summary and recommendations’.)

Thrombosis risk models — The use of models (eg, CHADS2, CHA2DS2-VASc) to determine the risk of thrombosis in patients with atrial fibrillation, and when to offer anticoagulation is discussed in depth elsewhere, and will be briefly reviewed here, since the patient’s thrombosis risk has a direct impact on the net overall benefit of anticoagulation (ie, thrombotic versus bleeding risk assessment). (See “Risk of embolization in atrial fibrillation”, section on ‘Risk models’.)

 

  • In a study of bleeding in elderly anticoagulated patients with atrial fibrillation, the rate of major hemorrhage (per 100 patient-years) was highest in those patients most in need for anticoagulation, as determined by their CHADS2 score (table 1), with rates of 2.0 to 4.3, and 20 to 23 for CHADS2 scores of zero to 2 and ≥3, respectively [25].
  • A separate study concluded that the risk of bleeding is high (eg, number needed to harm of 10) in AF patients ≥85 years of age with CHADS2 scores of 4 to 6, such that the use of anticoagulants should be highly individualized for this group [26].
  • In a mixed retrospective and prospective cohort study of 13,559 patients with nonvalvular AF, the rate of thromboembolism in patients not receiving warfarin increased 5.3-fold as the CHADS2 score increased from 1 to 4 or more, but the rate of intracerebral hemorrhage increased only 2.3-fold within this same CHADS2 interval [27].
  • Using data from the Birmingham Atrial Fibrillation in the Aged (BAFTA) trial, it was concluded that current thrombotic risk stratification methods in older patients with atrial fibrillation have only limited ability to predict for the risk of stroke [28]. It was suggested that there could be a pragmatic rationale for classifying all patients >75 as being at high risk for stroke until better tools are available.
  • A systematic literature search evaluated the association between CHADS2 covariates (ie, heart failure, hypertension, advanced age, diabetes, prior stroke/TIA, (table 1)) and the risk of bleeding in patients receiving treatment with warfarin. These associations were all found to be weak, with the exception of advanced age (age ≥75 years) [29].

 

The above observations present a major clinical dilemma in determining the degree of overall benefit in the elderly patient, who is simultaneously at increased risk for thromboembolism if anticoagulation is not given and at increased risk of bleeding if it is given. (See “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”, section on ‘Net clinical benefit’.)

RISK OF BLEEDING — There have been conflicting results concerning the role of age as an independent risk factor for anticoagulant-induced hemorrhage [10,30-34]. This issue was specifically addressed in a review of 4202 patients of the Leiden Anticoagulation Clinic treated because of mechanical heart valve prostheses, atrial fibrillation, or myocardial infarction [23]. The incidence rate of major hemorrhage (events per 100 patient-years) was noted to rise with increasing age, as noted above.

Similar results showing a significant correlation between age and major bleeding in anticoagulated older adults were also seen in a major Swedish study involving 18,391 patients [24]. (See ‘Effect of age’ above.)

Other variables that influence the risk of bleeding in the elderly include:

 

  • Predictors of ICH during anticoagulation with warfarin and related oral vitamin K antagonists have been defined, and overlap with risk factors for spontaneous ICH. These include advanced age [35], hypertension, prior history of cerebrovascular disease, and increased intensity of anticoagulation [25]. (See “Risk of intracerebral hemorrhage in patients treated with warfarin”, section on ‘High risk patients’ and ‘Bleeding risk models’ below and “Therapeutic use of warfarin”, section on ‘Bleeding’.)
  • Female sex — In a number of studies, the incidence of bleeding was noted to be higher in elderly women than in elderly men. (See “Therapeutic use of warfarin”, section on ‘Major risk factors’.)
  • Increased sensitivity to the effect of anticoagulation, perhaps due to enhanced receptor affinity or lower dietary vitamin K intake.
  • Concurrent use of the many drugs that increase bleeding risk (eg, aspirin, clopidogrel) or affect warfarin metabolism.
  • Associated comorbidity and other diseases that increase the risk of bleeding (eg, diverticulosis, malignancy, thrombocytopenia, bleeding diathesis).
  • Associated comorbidity or other diseases that increase the risk of trauma and falls (eg, peripheral neuropathy, gait instability). As an example, patients at high risk for falls with atrial fibrillation are at substantially increased risk of intracranial hemorrhage, especially traumatic intracranial hemorrhage [36].

 

The presence of cerebral amyloid angiopathy may be an important cause of warfarin-associated lobar intracerebral hemorrhage in the elderly [37]. However, this diagnosis cannot be made prior to the event, and cerebral amyloid angiopathy may simply provide an explanation for increased intracerebral bleeding in the elderly, irrespective of warfarin use. (See “Cerebral amyloid angiopathy”.)

Bleeding risk models — Advanced age (>75 years), intensity of anticoagulation (especially INR >4.0), history of cerebrovascular disease (recent or remote), uncontrolled hypertension, and concomitant use of drugs that interfere with hemostasis (aspirin or NSAIDs) are probably the most important variables determining an individual’s risk for major life-threatening bleeding complications while on warfarin therapy [10,33,34,38,39]. This subject is discussed in detail separately, but will be briefly reviewed here since the patient’s bleeding risk has a direct impact on the net overall benefit of anticoagulation (ie, thrombotic versus bleeding risk assessment). (See “Therapeutic use of warfarin”, section on ‘Bleeding’ and “Risk of intracerebral hemorrhage in patients treated with warfarin”.)

The systematic reviews that informed the evidence-based National Institute for Health and Clinical Excellence published guidelines on management of atrial fibrillation identified the following risk factors for bleeding with anticoagulation therapy, necessitating particular attention [40]:

 

  • Age >75 years
  • Concomitant use of antiplatelet drugs (eg aspirin, clopidogrel, nonsteroidal antiinflammatory drugs)
  • Multiple other drug treatments (ie, polypharmacy)
  • Uncontrolled hypertension
  • History of bleeding (eg, peptic ulcer, cerebral hemorrhage)
  • History of poorly controlled anticoagulation therapy

 

The assessment of bleeding risk should be part of the clinical assessment of patients before starting anticoagulation therapy. A number of bleeding risk models have been developed and validated to assist physicians in balancing the risks and benefits of antithrombotic therapy in outpatients treated with warfarin. Elderly patients feature as risk factors in all of these bleeding risk scores. In the case of atrial fibrillation, many risk factors for stroke are also risk factors for bleeding [41].

The two most commonly employed bleeding risk models for patients with AF are listed below and are discussed elsewhere in UpToDate.

HEMORR2HAGES risk index — The HEMORR2HAGES risk index is based upon 11 different risk factors for bleeding, including age >75 years. (See “Therapeutic use of warfarin”, section on ‘HEMORR2HAGES risk index’.)

HAS-BLED risk score — The HAS-BLED risk score (table 2) is based upon seven risk factors for bleeding, including age >65 years, and has been recommended within the European Society of Cardiology and Canadian guidelines for assessing the risk of bleeding in atrial fibrillation management. (See “Therapeutic use of warfarin”, section on ‘HAS-BLED bleeding risk score’.)

CONCERNS ABOUT VITAMIN K ANTAGONISTS

Increased sensitivity to warfarin — Elderly patients usually have increased sensitivity to the anticoagulant effect of warfarin as manifested by a decrease in the mean daily dose required to achieve a given anticoagulant intensity [12,34,42-44]. In one report, for example, patients ≥75 years of age needed less than one-half the daily warfarin dose compared with patients less than 35 years of age for an equivalent level of anticoagulation [43].

The mechanism(s) involved in the increased sensitivity to warfarin in the elderly are not clear. While pharmacokinetic-based warfarin dosing estimation algorithms add to our understanding of variability in warfarin dosing requirements, in one study they overestimated doses for older patients requiring the lowest doses of warfarin [45]. (See “Therapeutic use of warfarin”, section on ‘Pharmacokinetic and pharmacogenetic dosing’.)

Regardless of the mechanism(s) involved, initiation of warfarin therapy requires careful justification in the elderly, and overanticoagulation must be avoided [14,32,46].

Drug-drug interactions — Multiple drug therapy is common in elderly subjects due largely to age-related coexisting disease. It is therefore important to educate elderly persons about the importance of warfarin drug interactions any time their medication list is altered. (See “Therapeutic use of warfarin”, section on ‘Drug interactions’.)

A particularly relevant scenario exists in the elderly patient taking antibiotics. As an example, in a series of patients with coagulopathy induced by the combination of ciprofloxacin and warfarin, the median age was 72, the mean number of medications taken was 6.5, and the median INR was 10.0 [47]. This interaction may be especially important in hospitalized patients, who have a high incidence of vitamin K depletion, which potentiates the effect of an antibiotic-induced reduction in vitamin K-producing gut flora [48].

Aspirin and/or nonsteroidal anti-inflammatory drug use is common in the elderly; these drugs contribute to the risk of bleeding in patients treated with warfarin [49]. A particular problem arises in the setting of anticoagulated patients with atrial fibrillation who develop an acute coronary syndrome, with or without percutaneous coronary stenting, since aspirin plus clopidogrel is often prescribed in this setting [50]. Such triple antithrombotic drug therapy (ie, aspirin, clopidogrel, vitamin K antagonist) requires a fine balance between stroke prevention, recurrent coronary event(s), and bleeding [51]. (See “Therapeutic use of warfarin”, section on ‘Use of NSAIDs and antiplatelet agents’.)

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Initiation and monitoring — In view of the increased sensitivity of elderly patients to warfarin [52], an initial dose in the range of 3 to 5 mg/day is preferable in the older patient [6,53-58]. In patients at high risk of bleeding, and in those who are undernourished, debilitated, or have heart failure or liver disease, the starting dose should be even lower (table 3) [6]. As examples:

 

  • In a study of a large cohort of patients >70 years of age, it was estimated that an initiation dose of 5 mg/day of warfarin would be excessive for 82 percent of women and 65 percent of men [59]. (See “Therapeutic use of warfarin”, section on ‘Initial dose’ and “Therapeutic use of warfarin”, section on ‘Maintenance therapy’.)
  • In a study involving 187 elderly patients (mean age 85.6 years) utilizing a “geriatric dosing algorithm” in which the starting dose was 4 mg/day for the first three days, the mean daily maintenance dose of warfarin was 3.2 ± 1.5 mg/day (range: 1.0 to 7.0) for the derivation sample and 3.4 ± 1.5 (range: 1.0 to 7.0) mg/day for the validation sample [58].
  • A report from Sweden described the quality of anticoagulation in 18,391 patients from 67 different centers, in which the mean time in therapeutic range for all participants was 76 percent [24]. The mean daily dose of warfarin for these patients decreased significantly with increasing age, and was 5.6, 4.9, 4, 3.4, and 3 mg/day for those in the age ranges of 51 to 60, 61 to 70, 71 to 80, 81 to 90, and >90 years, respectively.

 

In less urgent cases, such as the initiation of anticoagulation for thromboprophylaxis in chronic atrial fibrillation, the estimated maintenance dose of warfarin can be used as the starting dose, adjusted as appropriate after five to seven days [55]. Initial dosing of dabigatran in AF is discussed separately. (See “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”, section on ‘Dabigatran’.)

Correcting excessive anticoagulation — An observational study evaluated the American College of Chest Physicians recommendations for the management of overanticoagulation (table 4), to determine their utility in elderly inpatients. After testing these guidelines in inpatients aged ≥75 years with an INR ≥5.0, it was concluded that they applied equally well to this group of patients [60]. (See “Correcting excess anticoagulation after warfarin”, section on ‘Treatment guidelines’.)

Dabigatran versus warfarin — An alternative anticoagulant to warfarin is the orally active direct thrombin inhibitor dabigatran, which is approved for use in atrial fibrillation. When compared with warfarin, dabigatran was associated with significantly lower rates of both embolic events and major bleeding events, although there was a trend towards a higher risk of major bleeding with dabigatran in those aged ≥75 years [61]. This has led to the recommendation in Europe to use the lower dose of dabigatran in older subjects.

The use of this agent is discussed in detail separately. (See “Anticoagulants other than heparin and warfarin”, section on ‘Dabigatran’ and “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”, section on ‘Dabigatran’.)

Since dabigatran does not require laboratory monitoring, may be less susceptible to dietary and drug interactions, and does not have warfarin’s narrow therapeutic window, its use may be attractive for the elderly patient who has limited ability to attend anticoagulation clinics, is taking multiple medications, and is at increased risk for bleeding and/or thrombosis. However, dabigatran requires twice daily dosing, has a higher pharmaceutical cost, lacks an antidote or reversing agent for the patient who bleeds while taking the drug, needs dose adjustment for decreased renal function, and lacks long-term safety data in older adults.

Underutilization of anticoagulation — Antithrombotic therapy continues to be underutilized in the older adult despite the compelling evidence of the benefits of stroke reduction in patients with atrial fibrillation in this age group (AF) [22,62]; it has been estimated that as few as 30 to 50 percent of elderly patients without a contraindication to anticoagulation are receiving warfarin therapy [63-65]. The range of findings can be illustrated by the following observations:

 

  • In a survey of anticoagulant usage in patients with AF, only 44 percent of patients with AF aged 65 to 74 years and 11 percent of patients over 75 years were treated with warfarin [63].
  • Among patients who were not anticoagulated in one series, a contraindication to warfarin was present in only 17 percent [66]. In addition, among those who were being treated with warfarin, the level of anticoagulation was often suboptimal [67].
  • In a chart review of Medicare patients in Connecticut, anticoagulation with warfarin was prescribed in only 53 percent of patients with AF and a prior stroke, a group at high risk for a recurrent event [68]. Even among those ideal candidates for anticoagulation who had AF, an increased risk of stroke, and a low risk of bleeding, only 62 percent were discharged from the hospital on a warfarin regimen.

 

VALUES AND PREFERENCES — When an elderly patient has an indication for anticoagulation, there is a compelling need for the clinician to offer the patient detailed information concerning the risks and benefits of such treatment. Similarly, there is an equally compelling need for the patient to understand these risks and benefits and to express to the clinician his/her values and preferences concerning which risk (eg, thrombosis or bleeding) is most worrisome. As an example, most clinicians are concerned about the risk of bleeding should anticoagulation be initiated in the older patient, while many patients are more fearful of the devastating effects of a thrombotic stroke should anticoagulation not be employed.

 

  • The use of thrombotic (CHADS2 score) (table 1) and bleeding risk models (HAS-BLED) (table 2) may help the clinician to determine the net benefit of anticoagulation.
  • The choice of anticoagulant (eg, warfarin or dabigatran) depends upon a number of factors and competing preferences, such as:

 

 

  • Warfarin: Need for periodic INR measurement, multiple drug interactions, narrow therapeutic window, known long-term side effects, availability of an effective antidote, low cost.
  • Dabigatran: No need for periodic laboratory testing, few drug interactions, unknown long term side effects, need for twice daily dosing, high cost, drug instability issues, lack of an antidote.

 

More specific guidance on this issue is presented separately. (See “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”, section on ‘Indications for and choice of therapy’.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

 

  • Basics topic (see “Patient information: Taking care of bruises (The Basics)”)
  • Beyond the Basics topics (see “Patient information: Warfarin (Coumadin®)”)

 

SUMMARY AND RECOMMENDATIONS — Many diseases associated with stroke and thromboembolism are more common with increasing age and appropriate anticoagulation therapy reduces morbidity and mortality.

Considerations about treatment choices — When considering anticoagulation in the elderly patient, it is useful to ask the following questions:

 

  • Is there a definite indication for anticoagulation (ie, a high risk of thrombosis if anticoagulation is not employed)? (See ‘Risk of stroke’ above and “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”.)
  • Is there a high risk of bleeding or strong contraindication against anticoagulation? (See ‘Risk of bleeding’ above.)
  • Will concurrent medications (eg, aspirin, clopidogrel, medications altering the metabolism of warfarin) or disease states (eg, renal disease) significantly increase bleeding risk or interfere with anticoagulation control? (See ‘Drug-drug interactions’ above.)
  • Are patient education, drug compliance, and attendance at an anticoagulant clinic for monitoring likely to be problems? (See “Outpatient management of oral anticoagulation”.)
  • Will there be regular discussions with the patient with regard to his/her understanding of the risks and benefits of continuing anticoagulation once it has been started?

 

Reducing the risk of bleeding — Careful and continuing evaluation is necessary to ensure that the risks of bleeding do not outweigh the benefits from anticoagulation. If anticoagulation has been decided upon, we suggest the following for reducing the bleeding risk:

 

  • Meticulous attention to the degree of anticoagulation when using a vitamin K antagonist, especially during the early phase (ie, first 90 days as well as the first year) of therapy, as well as in warfarin-naive patients. (See ‘Initiation and monitoring’ above.)
  • In patients with atrial fibrillation, use of the direct thrombin inhibitor dabigatran, which does not require anticoagulation monitoring, is an alternative to the use of a vitamin K inhibitor, and may be the preferred agent in some cases. (See “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”, section on ‘Summary and recommendations’.)
  • Aggressive management of excessive anticoagulation, if present. (See “Correcting excess anticoagulation after warfarin”, section on ‘Treatment’.)
  • Control of hypertension, if present. (See “Risk of intracerebral hemorrhage in patients treated with warfarin”, section on ‘Blood pressure control’.)
  • Interventions to reduce the risk of falls. (See “Falls in older persons: Risk factors and patient evaluation”.)
  • If warfarin is chosen as the anticoagulant, we suggest an initial dose in the range of 3.0 to 4.0 mg/day for the older patient and an initial dose of 2.5 mg/day if the patient is also frail, malnourished, or has liver disease (Grade 2B).

 

REFERENCES

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