Anticoagulation for elderly patients with atrial fibrillation: not to be neglected

Atrial fibrillation (AF) is a major health risk in the developed world and has a prevalence of around 5% in those aged under 65, rising to around 10% in the over 80 population. 1 , 2 It is estimated that 1% of the UK National Health Service expenditure is on AF, and therefore it poses a significant public and economic health burden. 3 Importantly, AF is associated with significant morbidity and mortality—in particular, it is a well-established, independent risk factor for stroke and estimates place this risk to be around 1.5% in the under 60 age group, rising to 23.5% in the over 80s. 4 The risk of stroke in AF is not homogeneous, and in a recent systematic review, four clinical features (prior stroke/TIA, advancing age, hypertension, and diabetes mellitus) were consistent independent risk factors for stroke among AF patients. 4 , 5 Of these, prior stroke/TIA was the most powerful risk factor and reliably conferred a high stroke risk (>5% per year, averaging 10% per year), whereas absolute stroke rates associated with other individual risk factors are difficult to precisely estimate from the available data. As these main risk factors are also highly prevalent in the aging population, it is therefore unsurprising that particularly the elderly are at a high risk of stroke. The use of oral anticoagulation (OAC) has been shown to reduce the risk of stroke by about two-thirds, in patients with non-valvular AF. 6 The most recent meta-analysis conducted by Hart et al . 7 reviewed the effectiveness of OAC from 29 trials that included 28 044 participants (mean age, 71 years; mean follow-up, 1.5 years). Compared with the control, adjusted-dose OAC (six trials, n = 2900) and antiplatelet agents (eight trials, n = 4876) reduced stroke by 64% (95% CI, 49–74%) and 22% (CI, 6–35%), respectively. Adjusted-dose OAC was also substantially more efficacious than antiplatelet therapy [relative risk (RR) reduction, 39% (95% CI, 22–52%)] (12 trials, n = 12 963). Thus, the judicious use of antithrombotic therapy is highly effective in reducing stroke for most patients with AF. Despite the overwhelming evidence supporting OAC for stroke prevention, it has long been recognized that OAC is still under prescribed, especially among elderly patients with AF. Certainly, this is of concern, as the highest risk group will obtain the least benefit. One review reported the prescription of OAC to patients with AF without contraindications to be between 15.2 and 78.8%. 8 Furthermore, a cross-sectional analysis from the ATRIA study cohort reported this figure to be only 55%. 9 Also, a prospective cohort study reported by Hylek et al . 10 showed only 51% of hospitalized elderly patients with AF were initiated on OAC. The many reasons behind the under utilization of OAC have been investigated and differences between patient and physician perspectives have been identified—physicians tending to underestimate to risk of stroke and overestimate the risk of haemorrhagic complications, and the converse applying to patients. 8 , 11–13 Additional factors—the frailty of elderly people, cognitive impairment, poor compliance of monitoring and treatment, falls risk, associated co-morbidity, and concomitant medications—have also been reported to reduce the initiation of OAC in elderly patients with AF. 14 The main concern—especially in elderly patients—taking OAC is a major cause of haemorrhage, where intracranial bleeding is the most dangerous, with an incidence of around 0.5% per year in patients receiving OAC. 15 In the meta-analysis by Hart et al ., 7 the absolute increases in major extracranial haemorrhage were small (≤0.3% per year) in trials, but sceptics would still argue that bleeding risks would be much higher in the non-trial setting. Many risk factors for major bleeding have been suggested, particularly, the intensity of anticoagulant effect (the higher the INR the greater this risk of haemorrhage) and various patient characteristics—increasing age, treated hypertension, cerebrovascular disease, ischaemic stroke, renal insufficiency, malignancy, and the use of concomitant medications. Increasing age has been suggested to substantially increase the risk of intracranial haemorrhage. 16 , 17 For example, Fang et al . 16 reported the risk of intracranial haemorrhage to be higher in patients older than 85 [adjusted odds ratio, 2.5 (95% CI, 1.3–4.7)]. Similarly, Torn et al . 17 reported an increase in the risk of major haemorrhage in the over 80 year olds as compared with those under 60—with a hazard ratio 2.7 (95% CI, 1.7–4.4). In contrast, a retrospective analysis conducted by Copland et al . 18 showed no significant difference in serious haemorrhagic complications between older and younger patients receiving warfarin with AF. Given the need to balance stroke prevention and the risk of bleeding in the elderly, the recent publication in The Lancet of Birmingham Atrial Fibrillation Treatment of the Aged Study (BAFTA) clinical trial is timely. 19 This UK Medical Research Council-funded randomized controlled trial in a primary care setting assessed the efficacy and safety of warfarin (INR, 2–3) compared with aspirin 75 mg in an elderly AF population (age > 75 years; N = 973 with mean age 81.5 years), who were followed up for a mean of 2.7 years. The primary endpoint was fatal or disabling stroke (ischaemic or haemorrhagic), intracranial haemorrhage, or clinically significant arterial embolism, which was significantly reduced in people assigned to warfarin compared with aspirin (annual risk, 1.8 vs. 3.8%; RR, 0.48; 95% CI, 0.28–0.80; P = 0.003; absolute annual risk reduction, 2%; 95% CI, 0.7–3.2). For the endpoint of stroke per se , the annual risk was also significantly reduced with warfarin vs. aspirin [1.6 vs. 3.4%; RR, 0.46 (0.26–0.79); P = 0.003] with the main benefit seen for severe or disabling stroke, rather than fatal strokes. Of note, the yearly risk of extracranial haemorrhage on warfarin was 1.4 vs. 1.6% on aspirin (RR, 0.87; 0.43–1.73; absolute risk reduction 0.2%, −0.7 to 1.2). This lack of difference in bleeding risk between warfarin and aspirin, in this elderly population, was a major observation in the BAFTA study. This trial therefore clearly supports the use of anticoagulation therapy for elderly patients with AF, in the absence of contraindications. Thus, elderly AF patients should not be denied OAC therapy, if appropriate. Clearly, stroke risk stratification needs to be balanced against contraindications to OAC, especially bleeding risk and the ability to cope with the dose variability (and thus, need for monitoring) and potential diet/drug interactions of OAC. Given the link between stroke and cardiovascular comorbidities in AF—especially in the elderly—optimized treatment of all treatable stroke risk factors, such as hypertension, 20 is mandatory. With such an approach, our management of elderly AF patients can only improve. Conflict of interest : G.L. has received funding for research, educational symposia, consultancy, and lecturing from different manufacturers of drugs used for the treatment of AF and thrombosis. He was Clinical Adviser to the Guideline Development Group writing the United Kingdom National Institute for Health and Clinical Excellence (NICE) Guidelines on AF management ( www.nice.org.uk ), and is on the writing committee for the American College of Chest Physicians Guidelines on Antithrombotic Therapy.