Digoxin vs. beta-blocker therapy in atrial fibrillation: analysis from the ESC-EHRA EORP Atrial Fibrillation General Long-Term (AFGen LT) Registry

Background There is a long-standing and unresolved controversy over the effects of digoxin on mortality. Furthermore, there is scarce evidence comparing the use of digoxin to beta-blocker in the general population with atrial fibrillation (AF). In this study, we aimed to evaluate the effects of digoxin over beta-blocker therapy among patients with AF. Methods Patients from the EORP-AF General Long-Term Registry with AF who were treated with either digoxin or beta-blocker were included. All patients were over 18 years old and had documented evidence of AF within 12 months prior to enrolment. The outcomes of interest were all-cause mortality, cardiovascular (CV) mortality, non-CV mortality and number of patients with unplanned hospitalisation (total and AF-related). These were recorded until the last known follow-up available. Results Of 6377 patients, 549 (8.6%) and 5828 (91.4%) were treated with digoxin and beta-blockers, respectively. Patients in the digoxin group were older (73 vs. 71 years, p<0.001) with reduced renal function (eGFR 65.4 vs. 68.7 mL/min/1.73m2, p=0.002), and had (in general) greater burden of comorbidities in terms of chronic kidney disease, chronic obstructive pulmonary disease, heart failure, hypertension and peripheral artery disease. Nonetheless, the use of anticoagulation therapy was comparable between both groups (p=0.112). Over 24 months follow-up, there were 550 (8.6%) all-cause mortality and 1304 (23.6%) patients with unplanned emergency hospitalisation. Digoxin use was associated with increased all-cause mortality (hazard ratio [HR] 1.90 [95% CI, 1.48–2.44]), both from CV and non-CV causes (CV: HR 2.21 [95% CI, 1.49–3.26]); non-CV: HR 1.70 [95% CI, 1.04–2.79]). There was no statistical difference in terms of unplanned emergency hospitalisation (HR 0.99 [95% CI, 0.80–1.21]) and AF-related hospitalisation (HR 0.78 [95% CI, 0.58–1.06]) between both groups. Using multivariable cox regression analysis, digoxin compared to beta-blocker therapy was independently linked to increased all-cause mortality (HR 1.52 [95% CI, 1.11–2.09]) and CV mortality (HR 1.82 [95% CI, 1.11–2.97]), but was not related to non-CV mortality (HR 1.31 [95% CI, 0.71–2.41]), emergency hospitalisation (HR 0.91 [95% CI, 0.71–1.16]) or AF-related hospitalisation (HR 0.88 [95% CI, 0.62–1.24]), after adjustment for known risk factors. Conclusion We demonstrated that the use of digoxin was independently associated with excess all-cause mortality, driven by CV death, but was non-inferior to beta-blocker in terms of preventing unplanned emergency or AF-related hospitalisation, after accounting for important risk factors. FUNDunding Acknowledgement Type of funding sources: None.

One‐Year Landmark Analysis of the Effect of Beta‐Blocker Dose on Survival After Acute Myocardial Infarction

Background Although beta‐blockers are recommended following myocardial infarction (MI), the benefits of long‐term treatment have not been established. The study's aim was to evaluate beta‐blocker efficacy by dose in 1‐year post‐MI survivors. Methods and Results The OBTAIN (Outcomes of Beta‐Blocker Therapy After Myocardial Infarction) registry included 7057 patients with acute MI, with 6077 one‐year survivors. For this landmark analysis, beta‐blocker dose status was available in 3004 patients and analyzed by use (binary) and dose at 1 year after MI. Doses were classified as no beta‐blocker and >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target doses used in randomized clinical trials. Age was 63 to 64 years, and approximately two thirds were men. Median follow‐up duration was 1.05 years (interquartile range, 0.98–1.22). When analyzed dichotomously, beta‐blocker therapy was not associated with improved survival. When analyzed by dose, propensity score analysis showed significantly increased mortality in the no–beta‐blocker group (hazard ratio,1.997; 95% CI, 1.118–3.568; P <0.02), the >0% to 12.5% group (hazard ratio, 1.817; 95% CI, 1.094–3.016; P <0.02), and the >25% to 50% group (hazard ratio, 1.764; 95% CI, 1.105–2.815; P <0.02), compared with the >12.5% to 25% dose group. The mortality in the full‐dose group was not significantly higher (hazard ratio, 1.196; 95% CI, 0.687–2.083). In subgroup analyses, only history of congestive heart failure demonstrated significant interaction with beta‐blocker effects on survival. Conclusions This analysis suggests that patients treated with >12.5% to 25% of the target dose used in prior randomized clinical trials beyond 1 year after MI may have enhanced survival compared with no beta‐blocker and other beta‐blocker doses. A new paradigm for post‐MI beta‐blocker therapy is needed that addresses which patients should be treated, for how long, and at what dose.

β-Adrenergic blockade in patients with dementia and hip fracture is associated with decreased postoperative mortality

Purpose Dementia, present in 20% of hip fracture patients, is associated with an almost threefold increase in postoperative mortality risk. These patients have a substantially higher incidence of cardiovascular, respiratory, and cerebrovascular mortality after hip fracture surgery compared to patients without dementia. This study aimed to investigate the association between beta-blocker therapy and postoperative mortality in patients with dementia undergoing hip fracture surgery. Methods This nationwide study included all patients in Sweden with the diagnosis of dementia who underwent emergency surgery for a hip fracture between January 2008 and December 2017. Cases where the hip fracture was pathological or conservatively managed were not included. Poisson regression analysis with robust standard errors was performed while controlling for confounders to determine the relationship between beta-blocker therapy and all-cause, as well as cause-specific, postoperative mortality. Results A total of 26,549 patients met the study inclusion criteria, of whom 8258 (31%) had ongoing beta-blocker therapy at time of admission. After adjusting for clinically relevant variables, the incidence of postoperative mortality in patients receiving beta-blocker therapy was decreased by 50% at 30 days [adj. IRR (95% CI) 0.50 (0.45–0.54), p < 0.001] and 34% at 90 days [adj. IRR (95% CI) 0.66 (0.62–0.70), p < 0.001]. Cause-specific mortality analysis demonstrated a significant reduction in the incidence of postoperative cardiovascular, respiratory, and cerebrovascular death within 30 and 90 days postoperatively. Conclusion Beta-blocker therapy is associated with decreased postoperative mortality in hip fracture patients with dementia up to 90 days after surgery. This finding warrants further investigation.

MO097BETA BLOCKER PREVENTS CARDIAC MOLECULAR AND MORPHOLOGICAL REMODELLING IN EXPERIMENTAL URAEMIA

Background and Aims Fifty years of heart failure research has shown that pathological cardiac remodelling forms a vicious cycle with myocardial dysfunction leading to progressive heart failure (HF) [Circulation, 102 IV14-23, 2000]. Fetal gene induction is associated with this process and beta blocker therapy has been shown to prevent it. Although chronic kidney disease (CKD) and HF share similar mediators of cardiac remodelling, the benefits of beta blocker therapy in CKD has not been studied. We, therefore, tested the hypothesis that beta blocker therapy prevents fetal gene induction and pathological cardiac remodelling in experimental uraemia. Method Wistar rats (n=32) had subtotal nephrectomy (STNx) [Frontiers in physiology, 10 1365, 2019] or sham surgery and were followed up for 10 weeks. The animals were randomly allocated to metoprolol (10mg/kg/day) or vehicle. In vivo and in vitro cardiac assessments were performed, and changes in myocardial fetal gene expression were also studied. Results Heart rate was significantly lower in metoprolol groups compared to untreated groups demonstrating effective beta blockade (Fig 1A). Echocardiographic LV mass was significantly higher in untreated STNx group compared to the metoprolol group (896.4 vs 632.2g, P=0.0004). Similar changes were seen with heart weight to tibia ratio (Fig 1B). There was no significant difference in blood pressure (BP) between treated and untreated STNx animals (123 vs 119 mmHg, P=0.359) (Fig 1A). STNx increased mRNA expression of fetal genes and there was a trend towards attenuation of this increase with beta blocker therapy (Fig 1C). Conclusion Beta blocker therapy ameliorates uraemic pathological cardiac remodelling irrespective of changes to BP. This benefit appears be associated with a reduction of induced fetal gene expression. Further translational research on the benefits of beta blockade in the treatment of uraemic cardiomyopathy is required.