Background Anemia frequently coexists with atrial fibrillation (AF) and has been variably associated with worse outcomes. We performed a systematic review and meta‐analysis to comprehensively assess the effect of anemia on mortality, stroke/systemic thromboembolism, and bleeding events in patients with AF. Methods MEDLINE and Embase were searched from inception until May 2020. Studies examining associations of anemia with the above outcomes in AF patients were included, and maximally adjusted hazard ratios (HRs) meta‐analysed. PROSPERO registration number CRD42020171113. Results Twenty‐eight studies involving 365 484 patients (41% female, mean age 74.7 years) were included. The average study follow‐up ranged from 0.2 to 4.0 years, and the prevalence of anemia was 16%. Anemia was associated with a 78% increase in all‐cause mortality (HR, 1.78; 95% confidence interval [CI], 1.44–2.20), 60% increase in cardiovascular mortality (HR, 1.60; 95% CI, 1.17–2.19), 134% increase in noncardiovascular mortality (HR, 2.34; 95% CI, 1.58–3.47) 15% increase in stroke/systemic thromboembolism (HR, 1.15; 95% CI, 1.01–1.31), 78% increase in major bleeding (HR, 1.78; 95% CI, 1.54–2.05), and 77% increase in gastrointestinal bleeding (HR, 1.77; 95% CI, 1.23–2.55). Sensitivity analyses including studies that reported odds ratios did not result in any material change. Conclusion Anemia is a frequently observed comorbidity in patients with AF, and is associated with an increased risk of all‐cause, cardiovascular and noncardiovascular mortality, stroke/systemic thromboembolism, and major and gastrointestinal bleeding. Future studies are required to explore the causes of anemia in AF, and whether investigation and treatment may be clinically beneficial in affected individuals.
Atrial fibrillation (AF) is the most common cardiac tachyarrhythmia and has a rising global prevalence. Given the increasing burden of AF-related symptoms and complications, new approaches to management are required. Anemia and iron deficiency are common conditions in patients with AF. Furthermore, emerging evidence suggests that the presence of anemia may be associated with worse outcome in these patients. The role of anemia and iron deficiency has been extensively explored in other cardiovascular states, such as heart failure and ischemic heart disease. In particular, the role of iron repletion amongst patients with heart failure is now an established treatment modality. However, despite the strong bidirectional inter-relationship between AF and heart failure, the implications of anemia and iron-deficiency in AF have been scarcely studied. This area is of mechanistic and clinical relevance given the potential that treatment of these conditions may improve symptoms and prognosis in the increasing number of individuals with AF. In this review, we summarise the current published literature on anemia and iron deficiency in patients with AF. We discuss AF complications such as stroke, bleeding, and heart failure, in addition to AF-related symptoms such as exercise intolerance, and the potential impact of anemia and iron deficiency on these. Finally, we summarize current research gaps on anemia, iron deficiency, and AF, and underscore potential research directions.
IntroductionAtrial fibrillation (AF) is associated with significantly impaired quality-of-life. Iron deficiency (ID) is prevalent in patients with AF. Correction of ID in other patient populations with intravenous iron supplementation has been shown to be a safe, convenient and effective way of improving exercise tolerance, fatigue and quality-of-life. The IRON-AF (Effect of Iron Repletion in Atrial Fibrillation) study is designed to assess the effect of iron repletion with intravenous ferric carboxymaltose in patients with AF and ID.Methods and analysisThe IRON-AF study is a double-blind, randomised controlled trial that will recruit at least 84 patients with AF and ID. Patients will be randomised to receive infusions of either ferric carboxymaltose or placebo, given in repletion and then maintenance doses. The study will have follow-up visits at weeks 4, 8 and 12. The primary endpoint is change in peak oxygen uptake from baseline to week 12, as measured by cardiopulmonary exercise testing (CPET) on a cycle ergometer. Secondary endpoints include changes in quality-of-life and AF disease burden scores, blood parameters, other CPET parameters, transthoracic echocardiogram parameters, 6-minute walk test distance, 7-day Holter/Event monitor burden of AF, health resource utilisation and mortality.Ethics and disseminationThe study protocol has been approved by the Central Adelaide Local Health Network Human Research Ethics Committee, Australia. The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12620000285954).
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