Europace Advance Access originally published online on March 8, 2008
Europace 2008 10(4):389-390; doi:10.1093/europace/eun054
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AFN MORTALITY AND THERAPY
Mortality in patients with atrial fibrillation: improving or not?
1 Hemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK; 2 Department of Cardiology, Hospital Virgen de la Arrixaca, Murcia, Spain
* Corresponding author. Tel: +44 121 5075080; fax: +44 121 554 4083. E-mail address: g.y.h.lip{at}bham.ac.uk
This editorial refers to ‘Mortality in patients with atrial fibrillation has significantly decreased during the last three decades: 35 years of follow-up in 1627 pacemaker patients’
by S. Asbach et al. on page 391
Atrial fibrillation (AF) is the commonest sustained arrhythmia, with an increasing incidence.1
With the increasing elderly population, the prevalence of AF is estimated to rise, conferring a significant mortality and morbidity. In the Framingham study, the presence of AF independently increased mortality in men by 1.5-fold and in women by 1.9-fold.2 Given that the average lifetime risk of developing AF is 
25%3 and the high economic cost associated with AF,4 it is clear that we are dealing with a condition with major public health implications.
The mortality and morbidity associated with AF are probably not homogeneous when taking into consideration related co-morbidities, complications, and treatment strategies. The lowest risk group is probably that with the so-called ‘lone AF’, which is essentially a diagnosis of exclusion, where AF is associated with no obvious pre-disposing factor on thorough clinical history and examination, with a structurally normal heart on echocardiography, normal ECG (except for AF), normal blood tests, and normal chest X-ray.5 As we recently highlighted, some series even report an increased mortality with lone AF patients.6 This may reflect how hard we look for associated co-morbidities, and furthermore, as patients get older, new co-morbidities will intervene.5
At the other extreme, the presence of AF in patients with acute coronary syndromes,7 congestive cardiac failure, and in the post-operative setting conditions associated with greater risk of adverse events. For example, an analysis from the TRAndolapril Cardiac Evaluation (TRACE)7 study reported AF to increase total mortality by 33%, with a risk ratio for sudden cardiac death (SCD) of 1.31 (95% CI: 1.07–1.60; P < 0.009). Furthermore, the adjusted risk ratio of AF for non-SCD was 1.43 (95% CI: 1.21–1.70; P < 0.0001). Similarly, data from the Framingham Heart Study8 reported that AF associated with the subsequent development of heart failure resulted in an increased mortality [men: hazard ratio (HR) 2.7, 95% CI: 1.9–3.7 and women: HR 3.1, 95% CI: 2.2–4.2]. Clearly, AF in association with heart disease is not a good combination.
Perhaps what has attracted much interest in AF is the morbidity and mortality associated with stroke and thrombo-embolism.9 Overall, AF increases the risk of stroke by up to 5-fold, but this risk is not homogeneous.9,10 Stroke risk in AF is increased with the presence of associated stroke risk factors such as previous stroke, increasing age, hypertension, diabetes mellitus, and so on—with the risk being cumulative with increasing co-morbidities.11,12 For example, this risk increases with age, with stroke occurring in 1.5% of the under 60 year olds and rising to 23.5% in the over 80s11 and is further increased (for example) by concomitant hypertension.
Given the improvements in the recognition and management of the co-morbid conditions associated with AF—especially hypertension, heart failure, and coronary artery disease—one would expect an improvement in the clinical outcome and prognosis of this arrhythmia. Is this really the case?
In a study from Olsted county of patients newly diagnosed with AF, Miyasaka et al.13 reported that mortality risk was high, especially within the first 4 months, but more importantly, there was no evidence for any significant changes over the 21 years in terms of overall mortality, early or late mortality, or mortality among patients without pre-existing cardiovascular disease. In this study, the Kaplan–Meier survival curves for the periods 1980–84, 1985–89, 1990–94, and 1995–2000 were essentially superimposed, and if we are really better with interventions for AF and its co-morbidities, we should perhaps have seen a difference in survival between the study periods. The lack of improved prognosis in this population study is clearly of concern.
If we are not improving mortality in the general AF population, is prognosis improving in specific patient groups? In the current issue of Europace, Asbach et al.14 investigated the impact of AF on mortality in 1627 patients with permanent pacemakers. With over 35 years of longitudinal data, patients were categorized into three decades according to the date of pacemaker implantation—1971–80 (the seventies, D1); 1981–90 (the eighties, D2) and 1991–2000 (the nineties, D3)—and the endpoint of the study being all-cause mortality. The mean survival times were 66.8, 75.7, and 139.8 months in the D1, D2, and D3 groups, respectively, with 5-year survival rates of 54.8, 57.3, and 67.4%, respectively.
Thus, things do appear to have improved somewhat in more recent times (1991–2000), but this analysis is (unfortunately) limited by the lack of data taking into account the associated co-morbidities and pharmacotherapy related to AF in this cohort of patients. Whether this is as a result of the better management of AF, its associated co-morbidities, or both is entirely speculative.
With the advances in the management of both AF and its co-morbidities, one would expect to see improvements in the mortality associated with this common arrhythmia. However, current mortality data in AF have significant limitations in that they are derived from dated cohorts, or clinical trial data sets with their inherent biases and limitations. Case ascertainment and data validation—especially of registry data—are crucial. Furthermore, such data often relate only to specific conditions associated with AF such as coronary artery disease and heart failure, and it is clear that some conditions (e.g. peripheral artery disease) are not systematically looked for.15 With AF becoming a growing epidemic, these epidemiological and prognostic estimations need very careful scrutiny and re-evaluation, so the impact of current guidelines and treatment strategies can be further refined and improved upon.
Conflict of interest: G.Y.H.L. has received funding for research, educational symposia, consultancy, and lecturing from different manufacturers of drugs used for the treatment of atrial fibrillation 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 atrial fibrillation management (www.nice.org.uk) and is on the writing committee for the American College of Chest Physicians Guidelines on Antithrombotic Therapy for Atrial Fibrillation.
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of Europace, the European Heart Rhythm Association or the European Society of Cardiology.
References
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[11] The Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology (2007) 69:546–54.
[12] Hughes M, Lip GYH. Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost (2008) doi:10.1160/TH07-08-0508.
[13] Miyasaka Y, Barnes ME, Bailey KR, Cha SS, Gersh BJ, Seward JB, et al. Mortality trends in patients diagnosed with first atrial fibrillation: a 21-year community-based study. J Am Coll Cardiol (2007) 49:986–92.
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[15] Lip GY. Coronary artery disease and ischemic stroke in atrial fibrillation. Chest (2007) 132:8–10.[CrossRef][Web of Science][Medline]
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- Mortality in patients with atrial fibrillation has significantly decreased during the last three decades: 35 years of follow-up in 1627 pacemaker patients
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Europace 2008 10: 391-394.[Abstract] [Full Text]
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