The impact of ethnicity on clinical outcomes in patients with heart failure and atrial fibrillation

Abstract Introduction Heart failure (HF) and atrial fibrillation (AF) are increasingly prevalent and associated with substantial morbidity (1,2). When HF and AF co-exist, the outcome profile is significantly worse than for either condition in isolation (3). Ethnic background is known to influence disease outcomes and treatment efficacy (4), but there is limited knowledge about how HF, AF and ethnicity interact on mortality and hospital admission. Purpose This study aims to address the null hypothesis of no difference in death and cardiovascular events comparing non-white and white patients with HF and concomitant AF, and assess the differential impact of ethnicity in patients with these conditions. Methods Individual patient data were obtained from 12 randomized controlled trials (RCTs) in patients with HF. RCT data were harmonised and meta-analysed to investigate the interaction of baseline heart rhythm (sinus rhythm versus atrial fibrillation) and ethnicity (non-white versus white). The primary outcome of all-cause mortality and secondary outcome of cardiovascular (CV)-related mortality were analysed using adjusted Cox regression models and propensity-score matching. Results 16,713 HF patients were included of which 1,899 (11%) were non-white, median age 66 (interquartile range [IQR] 57-73) and 4,703 (28%) women. During median follow-up of 1.4 years (IQR 0.8-2.3), death occurred in 394 (21%) non-white patients and 2,142 (15%) white patients; adjusted hazard ratio (HR) 1.36, 95% CI 1.20-1.54; p<0.001. The impact of ethnicity was greater in patients with coexisting HF and AF (non-white versus white HR 2.05; 95% CI 1.55-2.70; p<0.001), than in those with HF in sinus rhythm (non-white versus white HR 1.24; 95% CI 1.08-1.41; p=0.002). A significant interaction was evident between ethnicity and rhythm status for all-cause mortality (p=0.003), with similar findings using propensity-score matching (Figure 1). An exploratory analysis of beta-blockers versus placebo demonstrated divergent efficacy with respect to mortality for non-white (HR 1.00, 95% CI 0.79-1.27; p=0.99) and white patients (HR 0.70, 95% CI 0.63-0.78; p<0.001); p-interaction=0.008 (Figure 2). For cardiovascular hospitalisation, the non-white cohort also had higher rates, with greatest disparity in patients with combined HF and AF (non-white versus white HR 1.80, 95% CI 1.63-2.37; p<0.001) compared to HF in sinus rhythm (non-white versus white HR 1.23, 95% CI 1.11-1.36; p<0.001); p-interaction=0.012 in propensity-matching. Conclusion Non-white patients with HF suffer from substantially higher rates of death and hospitalisation than corresponding white patients, with the presence of comorbid AF significantly worsening this ethnicity-related disparity. In those with HF in sinus rhythm, beta blockers were found to be significantly less effective at reducing mortality in non-white patients.Figure 1 Figure 2