Safety of digoxin in nonagenarian patients with atrial fibrillation: lessons from the Spanish Multicenter Registry.

BACKGROUND: The association between digoxin and mortality is an unclear issue. In older patients with atrial fibrillation (AF), where use of digoxin is frequent, the evidence of its safety is scarce. Our aim is to assess the safety of digoxin in nonagenarian patients with AF. METHODS: We evaluated data from 795 nonagenarian patients with non-valvular AF from the Spanish Multicenter Registry. We analyzed the relationship between digoxin and all-cause mortality with the Cox proportional-hazards model. RESULTS: Follow-up was 27.7 ± 18.3 months. Mean age was 92.5 ± 3.8 years, and 71% of nonagenarian patients were female. Digoxin was not associated with increased risk of mortality [adjusted hazard ratio (aHR) = 1.16, 95% CI: 0.96-1.41,P = 0.130]. However, we found a significant increase in mortality in the subgroup with estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m 2 (aHR = 2.01, 95% CI: 1.13-3.57,P = 0.018), but not in the other subgroups of eGFR (30-59 mL/min per 1.73 m2 and ≥ 60 mL/min per 1.73 m2). When exploring the risk of mortality according to sex, male subgroup was associated with an increase in mortality (aHR = 1.48, 95% CI: 1.02-2.14,P = 0.041). This was not observed in females subgroup (aHR = 1.03, 95% CI: 0.81-1.29,P = 0.829). Based on the presence or absence of heart failure, we did not find significant differences (aHR = 1.20, 95% CI: 0.87-1.65,P = 0.268 vs. aHR = 1.15, 95% CI: 0.90-1.47,P = 0.273, respectively). CONCLUSIONS: In our large registry of nonagenarian patients with AF, we did not find an association between digoxin and mortality in the total sample. However, in the subgroup analyses, we found an increase in mortality with the use of digoxin in men and in patients with an eGFR < 30 mL/min per 1.73 m 2.

Incidence, predictors of bleeding and prognosis of bleeding in anticoagulated nonagenarian patients with atrial fibrillation.

BACKGROUND: The prevalence of atrial fibrillation (AF) increases with age. The prescription of anticoagulation in very elderly patients is controversial and sometimes underused. Our objective is to report the incidence and predictors of major bleeding in anticoagulated nonagenarian patients with non valvular atrial fibrillation (NVAF). METHODS: We analyzed a large multicentre registry of anticoagulated nonagenarian patients diagnosed with NVAF from three health areas of Spain, between 2013 and 2017. Predictors of major bleeding were studied with a competing risk analysis and the impact of major bleeding with a time-dependent mortality analysis. RESULTS: The incidence rate of major bleeding was 5 per100 person-year (95% Confidence Interval [CI]: 4.59-6.35), similar in the group of patients with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOAC). In the VKAs group we found as predictors of major bleeding: previous admission for bleeding (sub-distribution hazard ratio [sHR] 3.25, 95% CI: 1.48-7.13), creatinine (sHR 1.38, 95% CI: 1.16-1.64,) and control out-of-range INR (sHR 1.90, 95% CI: 1.02-3.55). In DOAC group, male sex (sHR 1.92, 95% CI: 1.18-3.13) and the history of previous admission for bleeding (sHR 2.60, 95% CI 1.33-5.06) were found as a predictor. The HAS-BLED was not associated with major bleeding. Major bleeding was associated with increased mortality in both VKAs and DOAC groups without significant differences. CONCLUSIONS: We found an incidence rate of major bleeding with relative low values, similar in those treated with VKAs and those treated with DOAC, with different predictors of major bleeding in each group. Major bleeding was associated with increased mortality, with no significant difference by oral anticoagulation therapy (OAT).

Vitamin K Antagonists and Direct Oral Anticoagulants in Nonagenarian Patients With Atrial Fibrillation.

OBJECTIVES: Nonagenarian patients are underrepresented in clinical trials that have evaluated oral anticoagulation in patients with atrial fibrillation (AF). The aim of this study was to assess the pronostic impact of oral anticoagulation in patients with AF age ≥90 years. DESIGN: Retrospective multicenter study of nonagenarian patients with AF. SETTING AND PARTICIPANTS: A total of 1750 nonagenarian inpatients and outpatients with nonvalvular AF between January 2013 and December 2018 in 3 Spanish health areas were studied. METHODS: Patients were divided into 3 groups based on antithrombotic therapy: nonoral anticoagulants (30.5%), vitamin-K antagonists (VKAs; 28.6%), and direct oral anticoagulants (DOACs; 40.9%). During a mean follow-up of 23.6 ± 6.6 months, efficacy outcomes (death and embolic events) were evaluated using a Cox regression analysis and safety outcomes (bleeding requiring hospitalization) by competing-risk regression. Results were complemented with a propensity score matching analysis. RESULTS: During follow-up, 988 patients died (56.5%), 180 had embolic events (10.3%), and 186 had major bleeding (10.6%). After multivariable adjustment, DOACs were associated with a lower risk of death and embolic events than nonanticoagulation [hazard ratio (HR) 0.75, 95% confidence interval (CI)] 0.61‒0.92), but VKAs were not (HR 0.87, 95% CI 0.72‒1.05). These results were confirmed after propensity score matching analysis. For bleeding, both DOACs and VKAs proved to be associated with a higher risk (HR for DOAC 1.43; 95% CI 0.97‒2.13; HR for VKA 1.94; 95% CI 1.31‒2.88), although findings for DOACs were not statistically significant (P = .074). For intracranial hemorrhage (ICH), only VKAs-not DOACs-presented a higher risk of ICH (HR 4.43; 95% CI 1.48‒13.31). CONCLUSIONS AND IMPLICATIONS: In nonagenarian patients with AF, DOACs led to a reduction in mortality and embolic events in comparison with nonanticoagulation. This reduction was not observed with VKAs. Although both DOACs and VKAs increased the risk of bleeding, only VKAs were associated with higher ICH rates.

Dietary Intake in Population with Metabolic Syndrome: Is the Prevalence of Inadequate Intake Influenced by Geographical Area? Cross-Sectional Analysis from PREDIMED-Plus Study.

Inadequate diet influences chronic diseases such as cardiovascular disease (CVD), the leading cause of death in Spain. CVD figures vary from one geographical region to another; this could be associated with different food choices. Our aim was to analyse the influence of geographical area on nutrient intakes among the Spanish adult population with Metabolic Syndrome (MetS). We analysed cross-sectional baseline data from the PREDIMED-Plus study: 6646 Spanish adults, aged 55⁻75 years, with overweight/obesity and MetS in four geographical areas. A validated 143-item Food Frequency Questionnaire (FFQ) was used to assess energy and nutrient intakes. The prevalence of inadequate nutrient intake was estimated according to Dietary Reference Intakes (DRIs). Multivariable-adjusted logistic regression was used to assess the relationship between geographical area (North, Central, East and South areas) and inadequate nutrient intake. People in the North area consumed significantly lower amounts of vegetables and fish but more sugar and alcohol (p < 0.001) than other areas. Dietary fibre, vitamin A, E, calcium and magnesium intakes were all lower among men of North area than in the other areas (p < 0.001). Sex (women), non-smoker and physical activity were also associated to adequate nutrient intake. Geographical area influences nutrient intakes. Its effect on dietary quality should be taken into account when planning food policies.