Is female sex a risk factor for stroke and thromboembolism in patients with atrial fibrillation? A systematic review and meta-analysis

BACKGROUND: Atrial fibrillation (AF) increases the risk of stroke, but this risk is not homogenous. Many risk factors contribute to stroke risk however, the evidence for female sex as a risk factor is less well-established. AIM: To perform a systematic review and meta-analysis of the available evidence to establish if female sex is a risk factor for stroke/thromboembolism among patients with AF. METHODS: A systematic literature search was conducted using Medline. The search term 'atrial fibrillation' was used in combination with 'stroke risk', 'thromboembolism', 'female' and 'gender differences' and returned 735 articles, of which 17 were appraised and included. Females with AF were compared with males with AF for the outcome of stroke/thromboembolism. RESULTS: Seventeen studies, 5 randomized-controlled trials and 12 prospective observational studies were included; 10 demonstrated an increased risk of stroke in women. Meta-analysis of the 17 studies revealed a 1.31-fold (95% confidence intervals (CIs) 1.18-1.46) elevated risk of stroke in women with AF; the risk appearing greatest for women aged ≥75 years. Only three studies compared entirely anticoagulated populations; stroke rates among these patients varied from 1.2-1.44% per-patient year for men and 2.08-2.43% per-patient year for women. Risk of stroke in women appeared similar regardless of oral anticoagulation therapy [risk ratio (95% CI 1.29 (1.09-1.52) and 1.49 (1.17-1.90) in non-anticogulated vs. anticoagulated/mixed cohorts, respectively). CONCLUSIONS: Women with AF are at increased risk of stroke, particularly elderly women. Comprehensive stroke risk assessment, including sex as a risk factor, should be undertaken in all AF patients.