Gender and contemporary risk of adverse events in atrial fibrillation

Abstract

Background and aims: The role of gender in decision-making for oral anticoagulation in patients with atrial fibrillation (AF) remains controversial.

Methods: The population cohort study used electronic healthcare records of 16 587 749 patients from UK primary care (2005-2020). Primary (composite of all-cause mortality, ischaemic stroke, or arterial thromboembolism) and secondary outcomes were analysed using Cox hazard ratios (HR), adjusted for age, socioeconomic status, and comorbidities.

Results: 78 852 patients were included with AF, aged 40-75 years, no prior stroke, and no prescription of oral anticoagulants. 28 590 (36.3%) were women, and 50 262 (63.7%) men. Median age was 65.7 years (interquartile range 58.5-70.9), with women being older and having other differences in comorbidities. During a total follow-up of 431 086 patient-years, women had a lower adjusted primary outcome rate with HR 0.89 vs. men (95% confidence interval [CI] 0.87-0.92; P < .001) and HR 0.87 after censoring for oral anticoagulation (95% CI 0.83-0.91; P < .001). This was driven by lower mortality in women (HR 0.86, 95% CI 0.83-0.89; P < .001). No difference was identified between women and men for the secondary outcomes of ischaemic stroke or arterial thromboembolism (adjusted HR 1.00, 95% CI 0.94-1.07; P = .87), any stroke or any thromboembolism (adjusted HR 1.02, 95% CI 0.96-1.07; P = .58), and incident vascular dementia (adjusted HR 1.13, 95% CI 0.97-1.32; P = .11). Clinical risk scores were only modest predictors of outcomes, with CHA2DS2-VA (ignoring gender) superior to CHA2DS2-VASc for primary outcomes in this population (receiver operating characteristic curve area 0.651 vs. 0.639; P < .001) and no interaction with gender (P = .45).

Conclusions: Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation.

Keywords: Atrial fibrillation; Gender; Sex; Stroke; Thromboembolism; Women.

Structured Graphical Abstract

The impact of gender on adverse events in patients with atrial fibrillation (AF) based on a population cohort study using electronic healthcare records from UK primary care (2005–20).

Figure 1

Variation in global use of gender for risk stratification in atrial fibrillation. Guidelines from different global regions showing marked variability in the use of gender as a discriminating factor for the prescription of oral anticoagulation in patients with AF. Further details are presented in Supplementary data online, Table S1. CCS = Canadian Cardiovascular Society; CHRS = Canadian Heart Rhythm Society; ESC = European Society of Cardiology; AHA = American Heart Association; ACC = American College of Cardiology; ACCP = American College of Clinical Pharmacy; HRS = Heart Rhythm Society; JCS = Japanese Circulation Society; JHRS = Japanese Heart Rhythm Society; SBC = Brazilian Society of Cardiology; SA Heart = South African Heart Association; APHRS = Asia-Pacific Heart Rhythm Society; CSANZ = Cardiac Society of Australia and New Zealand

Figure 2

Crude and adjusted primary outcome by gender. Cumulative event curves for the composite of all-cause mortality, ischaemic stroke, or arterial thromboembolism for women (solid green line) and men (dashed orange line). Presented as crude Kaplan–Meier curves (panel A) and after adjustment for age, socioeconomic deprivation status, and diagnoses of hypertension, diabetes mellitus, heart failure, and vascular disease (panel B)

Figure 3

Crude and adjusted secondary outcomes by gender. Cumulative event curves for ischaemic stroke or arterial thromboembolism and any stroke (ischaemia or haemorrhagic) or any thromboembolism (arterial or venous). Presented as crude Kaplan–Meier curves (panels A and C) and after multivariate adjustment (panels B and D) for women (solid green line) and men (dashed orange line)

Figure 4

Comparison of risk scores with and without gender. Comparison of the area under the receiver operator characteristic curve for the CHA₂DS₂-VA score (solid red line) and CHA₂DS₂-VASc score (dashed black line) for each outcome. Higher values indicate better accuracy, with the dashed grey line indicating accuracy no better than chance. Note patients with prior stroke or age ≥75 years were excluded to focus on a population where gender was a contributor to decision-making on oral anticoagulation; hence, these performance figures do not reflect the standard use of these risk scores

Figure 5

Primary outcome according to risk stratification. (A) Annualised crude event rate for the composite of all-cause mortality, ischaemic stroke, or arterial thromboembolism for each CHA₂DS₂-VA score according to gender; refer to Supplementary data online, Figure S7 for the secondary outcome of ischaemic stroke or arterial thromboembolism. (B) Age as a continuous variable using a cubic spline model in reference to age = 65 years and presented separately for women and men