Atrial fibrillation, anticoagulation, fall risk, and outcomes in elderly patients

doi:10.1016/j.ahj.2010.11.002

American Heart Journal

Volume 161, Issue 2, February 2011, Pages 241-246

https://doi.org/10.1016/j.ahj.2010.11.002 Get rights and content

Atrial fibrillation (AF) affects 2.5 million patients in the United States. The incidence of this condition increases with age, such that approximately 5% of people >65 years of age have AF. Because of the lack of organized atrial contraction and thrombus formation in the left atrium, patients with AF are at increased risk of stroke. The estimated risk of stroke among all AF patients is 5% per year. Among patients without mitral stenosis, there is a graded relationship of stroke risk with the number of CHADS₂ risk factors. Warfarin is the recommended treatment for embolic stroke prophylaxis in AF in intermediate- to high-risk patients. However, elderly patients who are deemed to be at risk of falls are often not started on warfarin therapy secondary to a perceived higher risk of bleeding complications. These risks have been evaluated, but conclusive data regarding the risk-benefit trade-off are elusive. This review summarizes available data on the use of warfarin in elderly patients with AF, focusing on the risk of bleeding, and will specifically address the utility of falls risk assessment in the decision to initiate warfarin therapy for AF.

Section snippets

Stroke prevention

Multiple clinical trials and subsequent meta-analyses have demonstrated the benefit of aspirin compared with placebo, as well as warfarin compared with placebo, in reducing stroke risk among AF patients (Table I). In a pooled analysis of 3 randomized controlled trials (RCTs), the Atrial Fibrillation Investigators found that the relative risk reduction for aspirin versus placebo was 21% (95% CI 0%-38%, P = .05).¹² In addition, another meta-analysis of 6 RCTs of aspirin versus placebo for stroke

Hemorrhagic complications

The relative benefit of warfarin compared with aspirin in preventing embolic stroke is known12, 13; however, warfarin therapy is not without risk. The association of hemorrhagic complications with warfarin use is well established, and elderly patients appear to be at higher risk.9, 16 In one analysis, when compared with patients <50 years of age, the unadjusted relative risk of patients ≥80 years of age having a life-threatening or fatal bleed on warfarin was 4.5 (95% CI 1.3-15.6); after

Warfarin monotherapy

Recommendations for anticoagulation therapy in AF patients should consider the balance of stroke risk, bleeding risk, and other complications of warfarin therapy, all of which appear to be at least in part associated with the intensity of anticoagulation. Prothrombin time ratio is a strong predictor of bleeding risk in all age groups.¹⁸ In addition, international normalized ratio (INR) may be associated with worse stroke outcomes. For example, in one study of AF patients taking warfarin who

Anticoagulation and risk of falls

Although increasing age is consistently associated with increased bleeding risk in warfarin therapy, an evaluation that specifically focused on fall-related hemorrhagic events showed that warfarin treatment was not associated with an increased risk of bleeding complications. In this study, the cohort treated with warfarin (379 falls patients) exhibited a hemorrhagic event rate of 6%, compared with 11% among patients (2,256 falls) not treated with warfarin (P = .01).²⁶ However, these results

Future directions

The ACTIVE trials explored the role of clopidogrel (an irreversible inhibitor of the platelet P2Y12 receptor) plus aspirin versus aspirin alone in warfarin-intolerant patients (ACTIVE A) and clopidogrel plus aspirin versus warfarin (ACTIVE W) in AF patients who were able to take warfarin.²⁷ These trials included patients with AF at enrollment or ≥2 episodes of AF in the previous 6 months, in addition to ≥1 of the following risk factors for stroke: age >74 years, hypertension, previous stroke or

Conclusions

The population of elderly patients with AF presents challenges with regard to the decision to provide anticoagulation treatment as well as which therapy, aspirin or warfarin, to choose. A higher likelihood of drug-drug interactions with warfarin, more adverse effects, and more comorbidities are at play in making these decisions. However, the available data suggest that physicians' decisions are guided more by their concerns over bleeding than an evaluation of the patient's risk for stroke; in

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Major trauma in older adults (MTOA) poses distinctive health and social care challenges, further underlined by the unique socioeconomic and geographical environment of Scotland. This study provides epidemiological trends of MTOA, to provide insight into areas where further evaluation and research are required.
Pseudonymised aggregated demographic, injury and outcome data from 2011 to 2020 were obtained from the Scottish Trauma Audit Group (STAG) Database, covering 28 hospitals across Scotland. Only individuals age ≥ 70 with an Injury Severity Score (ISS) > 15 were included.
There was an average of 216 annual cases of MTOA, with a 259 % rise in incidence from 2011 to 2020. This was predominantly driven by a rise in low velocity trauma (fall <2 m height; 287 % increase).
The proportion of all major trauma attributable to those aged ≥70 rose from 18.5 % in 2011 to 34.6 % in 2020. Death censored median (IQR) acute hospital length of stay was 18 days (9–30).
Overall, 30-day survival was 65.3 %, with no improvement seen between 2011 and 2020 (p = 0.50). Independent predictors of improved 30-day survival included Ages 70–79 & 80–89 [compared to reference ≥ 90] (OR 3.12; 95 %CI 2.24,4.31; p < 0.001 and OR 1.66; 95 %CI 1.21,2.29; p = 0.002 respectively), and Extremity injury (OR 1.89; 95 %CI 1.48,2.41; p < 0.001). Head injury (OR 0.72; 95 %CI 0.54,0.96; p = 0.027) and increasing ISS score (OR 0.88, 95 %CI 0.86,0.89; p < 0.001) were associated with lower likelihood of 30-day survival. A further model also including the admission ward (from eSTAG data November 2017 onwards) demonstrated an association with reduced 30-day survival with admission to General Surgery (OR 0.42; 95 %CI 0.19,0.93; p = 0.033), Intensive Care (OR 0.25; 95 %CI 0.10,0.60; p = 0.002) and Medical Specialities (OR 0.33; 95 %CI 0.15,0.73; p = 0.007) compared to the reference (Major Trauma).
Exponential Smoothing predictions revealed a further potential 184 % rise in incidence of MTOA from 2021 to 2030 (3657 per 100,000 population at risk to 10,392 per 100,000 population at risk).
MTOA is likely to be a rising health care burden, requiring larger quantities of health and social care resource. Urgent preventative strategies are required to reduce low velocity trauma (standing height falls), as well as the high mortality and morbidity of MTOA.
Age-related cardiovascular changes and diseases
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Longevity is increasing and the population of older adults is expanding. The elderly requires dedicated therapeutic medical care due to multiple comorbidities. The prevalence and mortality with most cardiovascular diseases increase with age. Two-thirds of people > 60 years and more than 85% of people >85 years have some form of cardiovascular disease. In addition, what is regarded as “normal” for this population is different from that of the general population. This chapter will provide an overview of age-related, physiological/pathologic cardiovascular changes related to ageing.
Characteristics of warfarin under-prescription in older adults with atrial fibrillation
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The prevalence of atrial fibrillation (AF) and atrial flutter (AFl) increases with age. Under-prescription of anticoagulants in older adults can lead to increased morbidity and mortality. We analyzed warfarin prescription patterns in older adults.
In this observational single-center study, we analyzed 2179 consecutive patients with admission diagnosis of AF or AFl. Patients were divided into “older” (≥ 75 years old) and “younger” (<75 years old) groups. Prescription patterns of warfarin were analyzed. Patients discharged from the hospital on a non-warfarin anticoagulation were excluded.
Of the 1988 patients analyzed, 46.9% were ≥75 years old, of which 50.8% were prescribed warfarin. There was no association between mean CHA₂DS₂-VASc score and warfarin prescription on discharge (OR = 1.06 (95% CI 0.93–1.21), p = 0.388) in the older group. After adjusting for hypertension, renal function, and Black race, warfarin prescription in older adults was independently associated with lower aspirin prescription rates (OR = 0.57 (95% CI 0.43–0.75), p < 0.001), lower body mass index (OR = 1.03 (95% CI 1.01–1.06), p = 0.018), and lower hemoglobin levels (OR = 1.11 (95% CI 1.04–1.19), p = 0.002).
In our study, older adults (≥75 years old) with AF and AFl tended to have lower rates of warfarin prescription despite higher CHA₂DS₂-VASc score and higher risk of thromboembolic events. Anemia, lower body weight, and aspirin use were characteristics associated with warfarin under-prescription.
Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation with warfarin or edoxaban: An in-depth analysis from the ENGAGE AF-TIMI 48 randomized trial
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Citation Excerpt :
Similarly, a post-hoc analysis of the ENGAGE AF-TIMI 48 trial suggested that patients at risk for falling may be less likely to suffer ICH with edoxaban than warfarin [14]. However, risk of oral anticoagulation in AF patients more likely to fall may be overestimated [22–24], and risk of traumatic ICH should be balanced with the potential benefit of preventing ischemic stroke [25]. Together, our data suggest ways in which ICH risk can be modified in the setting of oral anticoagulation: managing high blood pressure [26], avoiding concomitant use of platelet inhibitors whenever possible [27], and treating patients with high-risk features for bleeding (older age, high risk for falls, prior stroke/TIA, non-Caucasian race, low body weight, low platelet count) with a NOAC instead of warfarin.
Intracranial hemorrhage (ICH) is a known risk of oral anticoagulation; delineating ICH attributes may provide nuanced guidance regarding atrial fibrillation management. We evaluated ICH characteristics and outcomes from Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48), a randomized trial that compared two edoxaban regimens (higher-dose edoxaban regimen 60/30 mg (HDER), lower-dose edoxaban regimen 30/15 mg (LDER)) with warfarin in patients with atrial fibrillation. Patients who suffered ICH vs those who did not were compared and independent predictors of ICH were calculated. We also assessed ICH subtype and etiology. Of 21,105 randomized patients, 322 (1.53%) had ≥ 1 ICH for a total of 368 events. Intraparenchymal hemorrhage (HDER: HR 0.52 [95% CI 0.35–0.77], LDER: HR 0.22 [0.13–0.38]) and subdural hematoma (HDER: HR 0.29 [0.15–0.55], LDER: HR 0.26 [0.13–0.50]) were lower with both HDER and LDER vs warfarin. Subarachnoid hemorrhage frequency was similar in the HDER vs warfarin groups but lower in LDER. Compared to warfarin, edoxaban was associated with lower risk of spontaneous ICH (HDER: HR 0.47 [0.31–0.69], LDER: HR 0.34 [0.22–0.53]) and traumatic ICH (HDER: HR 0.32 [0.17–0.61], LDER: HR 0.31 [0.16–0.59]). In multivariable analysis, randomization to warfarin, increased age, and risk of falling remained independent predictors of ICH. In ENGAGE AF-TIMI 48, ICH was decreased in edoxaban-treated patients compared to warfarin-treated patients, including ICH of both spontaneous and traumatic causes. Both edoxaban regimens lowered intraparenchymal and subdural hemorrhages compared to warfarin. Patient characteristics and medical history may help guide anticoagulation management.
Contemporary approach to stroke prevention in atrial fibrillation: Risks, benefits, and new options
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Citation Excerpt :
Furthermore, a meta-analysis of elderly patients with AF at increased risk for falls showed that quality-adjusted life expectancy was higher with warfarin use than with aspirin use or no therapy unless the patient's annual risk of stroke was <2% per year [62]. The authors asserted that risk of falling should not be an important factor in determining candidacy for anticoagulation and that one would have to fall 300 times/year for the risk of fall-related bleeding complications to outweigh the benefits of anticoagulation [62,63]. As discussed earlier, DOACs have a lower risk of hemorrhagic stroke and do not share the disadvantages of therapeutic drug monitoring and narrow therapeutic index with warfarin.
Atrial fibrillation is a common diagnosis affecting nearly 3 million adults in the United States. Morbidity and mortality in these patients is driven largely by the associated increased risk of thromboembolic complications, especially stroke. Atrial fibrillation is a stronger risk factor than hypertension, coronary disease, or heart failure and is associated with an approximately five-fold increased risk. Mitigating stroke risk can be challenging and requires accurate assessment of stroke risk factors and careful selection of appropriate therapy. Anticoagulation, including the more recently introduced direct oral anticoagulants, is the standard of care for most patients. In addition, emerging non-pharmacologic mechanical interventions are playing an expanding role in reducing stroke risk in select patients. In this review we highlight the current approach to stroke risk stratification in atrial fibrillation and discuss in detail the mechanism, risks, and benefits of current and evolving therapies.
Use of oral anticoagulants in complex clinical situations with atrial fibrillation
2018, Medicina Clinica
En el presente capítulo se actualiza el tratamiento anticoagulante en pacientes con fibrilación auricular y diferentes situaciones clínicas que requieren consideraciones particulares, como son la cardiopatía isquémica, la cardioversión eléctrica, la ablación de venas pulmonares, la presencia de valvulopatías con o sin prótesis, la insuficiencia renal o la ancianidad y fragilidad. En pacientes con fibrilación auricular no valvular, la presencia de insuficiencia renal incrementa tanto el riesgo trombótico como el hemorrágico. En los estadios leves y moderados, los anticoagulantes de acción directa mostraron un mayor beneficio que warfa-rina, aunque suelen requerir ajuste de dosis. En el estadio de fallo renal/diálisis, no hay evidencia sólida de que la warfarina resulte beneficiosa y la utilización de los anticoagulantes de acción directa no está recomendada. Por su fisiopatología, se ha considerado que la anticoagulación oral podría ejercer un efecto beneficioso en los pacientes con cardiopatía isquémica. Sin embargo, los anticoagulantes antivitamina K no han demostrado una relación riesgo-beneficio satisfactoria. Por el contrario, los anticoagulantes de acción directa, en dosis reducidas, podrían ejercer un efecto beneficioso en este escenario en asociación con los antiagregantes.
El uso de los anticoagulantes de acción directa previo a la cardioversión eléctrica en pacientes con fibrila-ción auricular no valvular parece tener asociado un riesgo de eventos cardioembólicos, al menos comparable a los anticoagulantes antivitamina K, evitando la demora en aplicar esta técnica en pacientes sin niveles adecuados de INR precardioversión eléctrica. En el contexto de su uso periablación de fibrilación auricular, el dabigatrán y el rivaroxabán demostraron al menos no inferioridad respecto a los anticoagulantes antivitamina K en cuanto a seguridad.
La coexistencia de cualquier tipo y grado de valvulopatías con la fibrilación auricular obliga a evaluar la in-dicación de tratamiento antitrombótico de la misma manera que si no existiera valvulopatía. Cuando sea necesaria la anticoagulación, los anticoagulantes de acción directa son de elección en casi todas las situaciones, excepto en los pacientes portadores de una prótesis mecánica o que padezcan enfermedad mitral reumática significativa, que deben tratarse con anticoagulantes antivitamina K. La elección de la estrategia antitrombótica adecuada en el anciano frágil es una cuestión compleja en que interfieren múltiples factores, más allá de la evaluación del riesgo embólico y hemorrágico. La realización de una evaluación geriátri-ca integral es fundamental para que la decisión final sea individualizada. Además, esta se debe consensuar y revaluar periódicamente. Los anticoagulantes de acción directa podrían ser la alternativa más favorable en la mayoría de los pacientes ancianos con fibrilación auricular no valvular.
The present article provides an update on anticoagulant treatment in patients with atrial fibrillation in distinct clinical scenarios requiring particular considerations, such as ischaemic heart disease, electrical cardioversion, pulmonary vein ablation, the presence of valvular disease with or without prosthetic valves, and renal insufficiency, as well as old age and frailty. In patients with non-valvular atrial fibrillation, the presence of renal insufficiency increases both thrombotic and haemorrhagic risk. In mild and moderate stages, direct-acting anticoagulants confer a greater benefit than warfarin, although they usually require dose adjustment. In renal failure/dialysis, there is no solid evidence that warfarin is beneficial and the use of direct-acting anticoagulants is not recommended. Because of its pathophysiology, oral anticoagulation could have a beneficial effect in patients with heart disease. However, vitamin K antagonists have not shown a satisfactory risk-benefit ratio. In contrast, direct-acting anticoagulants, at reduced doses, could have a beneficial effect in this scenario in association with antiplatelet agents.
The use of direct-acting anticoagulants prior to electrical cardioversion in patients with non-valvular atrial fibrillation seems to be associated with a risk of cardioembolic events that is at least comparable to that of vitamin K antagonists. Their use avoids delay in the application of electrical cardioversion in patients without adequate INR levels. In the context of their use before and after atrial fibrillation ablation, dabiga-tran and rivaroxaban have demonstrated at least non-inferiority with vitamin K antagonists in terms of safety.
In patients with any type or grade of valvular disease and atrial fibrillation, the indication of antithrombo-tic treatment must be evaluated in the same way as in patients with atrial fibrillation and no valvular di-sease. Whenever anticoagulation is required, direct-acting anticoagulants are the treatment of choice in nearly all situations, except in patients with mechanical valves or who have significant rheumatic mitral disease, who should be treated with vitamin K antagonists. The choice of appropriate antithrombotic stra-tegy in frail elderly patients is complex and involves multiple factors beyond assessment of embolic and haemorrhagic risk. Comprehensive geriatric assessment is essential for an individualised final decision. Moreover, any such decision should be consensus-based and periodically reviewed. Direct-acting anticoa-gulants could be the most beneficial alternative in most elderly patients with non-valvular atrial fibrillation.

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: George J. Klein, MD served as guest editor for this article.

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Curriculum in CardiologyAtrial fibrillation, anticoagulation, fall risk, and outcomes in elderly patients

Section snippets

Stroke prevention

Hemorrhagic complications

Warfarin monotherapy

Anticoagulation and risk of falls

Future directions

Conclusions

J Am Med Dir Assoc

Am J Med

Am J Med

Chest

Lancet

Am Heart J

Am Heart J

Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications

Arch Intern Med

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

Use of anticoagulation in elderly patients with atrial fibrillation who are at risk for falls

Ann Pharmacother

Stroke severity in atrial fibrillation. The Framingham Study

Stroke

Anticoagulant-related bleeding in older persons with atrial fibrillation: physicians' fears often unfounded

Arch Intern Med

Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials

JAMA

The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage

Arch Intern Med

Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls

Arch Intern Med

The efficacy of aspirin in patients with atrial fibrillation. Analysis of pooled data from 3 randomized trials. The Atrial Fibrillation Investigators

Arch Intern Med

Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis

Ann Intern Med

Circulation

Curriculum in Cardiology
Atrial fibrillation, anticoagulation, fall risk, and outcomes in elderly patients