Atrial Fibrillation and Hormone Replacement Therapy
Hormone replacement therapy (HRT) does not independently increase the risk of stroke, thromboembolism, bleeding, or mortality in women with atrial fibrillation, and standard stroke prevention strategies should be applied based on thromboembolic risk scores regardless of HRT use. 1
Evidence on HRT Safety in AF
The most definitive evidence comes from the AFFIRM trial analysis, which examined 1,594 women with AF, of whom 376 (23.6%) were taking HRT at baseline. 1 This study demonstrated:
- No increased risk of the composite primary endpoint (all-cause death, stroke, systemic/pulmonary embolism, and myocardial infarction) with HRT use (hazard ratio 0.894; 95% CI, 0.658-1.214; P=0.473) 1
- No increased risk of any individual secondary outcome including stroke, thromboembolism, or major bleeding 1
- Confirmation in propensity score-matched analysis (hazard ratio 0.966; 95% CI, 0.663-1.409; P=0.858), strengthening the validity of these findings 1
Risk Stratification Approach
The actual predictors of adverse outcomes in women with AF are traditional risk factors, not HRT status:
Apply the CHA₂DS₂-VA score to assess stroke risk in all women with AF, regardless of HRT use. 2 Female gender itself is recognized as an independent stroke risk factor in AF, and women may derive greater benefit from anticoagulation than men. 3
Anticoagulation Recommendations
For women with AF on HRT, follow standard anticoagulation guidelines:
- CHA₂DS₂-VA score ≥2: Oral anticoagulation is recommended 2
- CHA₂DS₂-VA score of 1: Oral anticoagulation should be considered 2
- Prefer DOACs over warfarin (apixaban, dabigatran, edoxaban, rivaroxaban) due to reduced intracranial hemorrhage risk 2, 4
- Target INR 2.0-3.0 if warfarin is used 5
Clinical Pitfalls to Avoid
- Do not withhold or discontinue anticoagulation solely because a patient is taking HRT, as HRT does not increase thromboembolism risk in the context of AF 1
- Do not substitute aspirin for anticoagulation in women at elevated stroke risk, as aspirin has poorer efficacy and is not recommended for stroke prevention in AF 4
- Ensure adequate anticoagulation intensity: In the Japanese cohort study, 75% of thromboembolic events during warfarin therapy occurred when INR was below optimal levels 6
- Recognize that women have greater thromboembolic risk when not anticoagulated but may benefit from greater risk reduction when properly anticoagulated 3
Rate and Rhythm Control
Standard AF management strategies apply to women on HRT:
- Beta-blockers or calcium channel antagonists (diltiazem, verapamil) for rate control 2, 7
- Consider early rhythm control for symptomatic patients or within 12 months of diagnosis to reduce cardiovascular death or hospitalization 2
- Catheter ablation as first-line therapy for symptomatic paroxysmal AF to improve symptoms and slow progression 4