Associations of anemia with stroke, bleeding, and mortality in atrial fibrillation: A systematic review and meta-analysis

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.