Search

Aims Elevated serum uric acid concentration (SUA) has been associated with an increased risk of cardiovascular disease, but this may be due to unmeasured confounders. We examined the association between SUA and outcomes as well as the effect of sacubitril/valsartan on SUA in patients with heart failure with reduced ejection fraction (HFrEF) in PARADIGM-HF. ..................................................................................................................................................................... Methods and results The association between SUA and the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 8213 patients using quintiles (Q1–Q5) of SUA adjusted for baseline prognostic variables including estimated glomerular filtration rate (eGFR), diuretic dose, and log N-terminal pro-brain natriuretic peptide. Change in SUA from baseline over 12 months was also evaluated in each treatment group. Patients in Q5 (SUA ≥8.6 mg/dL) compared with Q1 ( < 5.4 mg/dL) were younger (62.8 vs. 64.2 years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123 mmHg), lower eGFR (57.4 vs. 76.6 mL/min/1.73 m2), and greater diuretic use. Higher SUA was associated with a higher risk of the primary outcome (adjusted hazard ratios) Q5 vs. Q1=1.28 [95% confidence intervals (1.09–1.50), P =0.003], cardiovascular death [1.44 (1.11–1.77), P =0.001], HF hospitalization [1.37 (1.11–1.70), P =0.004], and all-cause mortality [1.36 (1.13–1.64), P =0.001]. Compared with enalapril, sacubitril/valsartan reduced SUA by 0.24 (0.17–0.32) mg/dL over 12 months (P < 0.0001). Sacubitril/valsartan improved outcomes, irrespective of SUA concentration. ..................................................................................................................................................................... Conclusion Serum uric acid concentration was an independent predictor of worse outcomes after multivariable adjustment in patients with HFrEF. Compared with enalapril, sacubitril/valsartan reduced SUA and improved outcomes irrespective of SUA.

Objectives: This study sought to assess safety and effectiveness of low-dose aspirin in heart failure (HF) not complicated by atrial fibrillation. Background: Despite lack of evidence, low-dose aspirin is widely used in patients with HF and sinus rhythm with and without prior ischemic heart disease. Methods: The study included 12,277 patients with new-onset HF during 2007 to 2012 who had no history of atrial fibrillation. Of 5,450 patients using low-dose aspirin at baseline, 3,840 were propensity matched to non-aspirin users in a 1:1 ratio. Propensity-matched Cox models were calculated with respect to the primary composite outcome of all-cause mortality, myocardial infarction, and stroke and the secondary outcomes of bleeding and HF readmission. Results: The composite outcome occurred in 1,554 (40.5%) patients in the aspirin group and 1,604 (41.8%) patients in the non-aspirin group. Aspirin use was not associated with an altered risk of composite outcome (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.91 to 1.05), but it was associated with an increased risk of myocardial infarction (HR: 1.34; 95% CI: 1.08 to 1.67), whereas no differences were observed in all-cause mortality and stroke. An increased risk of HF readmission was observed in the aspirin group (HR: 1.25; 95% CI: 1.17 to 1.33). No difference in bleeding was observed. In subgroup analyses on the basis of a history of ischemic heart disease, the results were similar to the main result. Conclusions: No association was detected between low-dose aspirin use and the composite outcome of all-cause mortality, admission for myocardial infarction, and admission for stroke in patients with HF with no history of atrial fibrillation. Aspirin use was associated with an increased risk of readmission for HF.

Background: Employment status at time of first heart failure (HF) hospitalization may be an indicator of both self-perceived and objective health status. In this study, we examined the association between employment status and the risk of all-cause mortality and recurrent HF hospitalization in a nationwide cohort of patients with HF. \ud Methods and Results: We identified all patients of working age (18-60 years) with a first HF hospitalisation in the period 1997-2015 in Denmark, categorized according to whether or not they were part of the workforce at time of the index admission. The primary outcome was death from any cause and the secondary outcome was readmission for HF. Cumulative incidence curves, binomial regression and Cox regression models were used to assess outcomes. Of 25571 patients with a first hospitalization for HF, 15428 (60%) were part of the workforce at baseline. Patients in the workforce were significantly younger (53 vs. 55 years) more likely to be male (75% vs 64%) and less likely to have diabetes (13% vs 22%) and chronic obstructive pulmonary disease (5% vs 10%), all p-values

Aims: Because of concerns about the safety of aliskiren in patients with diabetes, study treatment was stopped prematurely in the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE). We examined outcomes and treatment effect in these patients compared with those without diabetes. Methods and results: ATMOSPHERE included 7016 patients with heart failure and a reduced ejection fraction (HFrEF) randomly assigned to enalapril plus aliskiren, aliskiren alone, or enalapril. At baseline, 1944 (27.7%) patients had diabetes. Median follow-up was shorter in patients with diabetes compared with those without (24 months vs. 46 months). Among patients with diabetes, the primary endpoint of cardiovascular death or hospitalization for heart failure occurred in 216 patients (33.1%) in the enalapril group (reference), 172 (27.4%) in the aliskiren group [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.67–1.00; P = 0.053], and 196 (29.5%) in the combination group (HR 0.86, 95% CI 0.71–1.04; P = 0.13). The effects of the treatments studied did not differ significantly compared with patients without diabetes. In patients with diabetes, aliskiren monotherapy was associated with a lower risk of symptomatic hypotension compared to enalapril [42 (6.7%) vs. 65 (10.0%); P = 0.04], whereas other adverse events were generally balanced between the three groups. Conclusion: In patients with HFrEF and diabetes, there was no signal of harm and a trend towards benefit when direct renin inhibition monotherapy was compared with an angiotensin-converting enzyme inhibitor, whereas combined aliskiren and enalapril treatment led to more adverse events with no improvement in outcomes. Treatment effects did not differ in patients with diabetes compared with those without.

Background: Heart failure (HF) has a major impact on a patient’s quality of life and functional\ud status. This impact may be sufficiently profound to prevent independent living although how\ud often this is the case is unknown. We examined the need for domiciliary assistance and admission\ud to a nursing home following first HF hospitalization.\ud Methods: In nationwide Danish registries, we identified a cohort of patients discharged alive\ud after a first-time HF hospitalization in the period 2008–2014 who were matched 1:5 with comparison\ud subjects based on age and sex and followed for 5 years.\ud Results: We included 37,547 patients (69% men) discharged after a first-time HF-hospitalization\ud and 187,735 comparison subjects. The 5-year incidence of initiation of domiciliary care was\ud 24.1% [23.7%–24.6%] among HF patients and 9.2% [9.1%–9.4%] among the comparison\ud cohort and yielded a corresponding adjusted HR of 2.02 [1.96–2.09]. Covariates associated with\ud initiation of domiciliary support included older age (HR 1.08 [1.07–1.08] per 1 year increase\ud in age), living alone (HR 2.09 [2.04–2.15]) and comorbidities. The 5-year incidence of nursing\ud home admission was 3.9% [3.7%–4.0%] among HF patients and 1.7% [1.7%–1.8%] among the\ud comparison cohort and this resulted in an adjusted HR of 1.91 [1.77–2.06]. Covariates associated\ud with nursing home admission included older age (HR 1.10 [1.10–1.11]), living alone (HR\ud 2.15 [2.02–2.28]) and history of stroke (HR 2.71 [2.53–2.90]).\ud Conclusion: Hospitalization for HF is associated with increased need for domiciliary support\ud and nursing home admissions. Older age, living alone, and comorbidities were associated with\ud higher risk of both outcomes.

Objectives:\ud This study investigated the association between the use of evidence-based medicine (EBM) for heart failure (HF) and risk of workforce detachment.\ud \ud Background:\ud The ability to work can be a marker of functional capacity and quality of life.\ud \ud Methods:\ud We examined a nationwide cohort of patients in the workforce 1 year after first hospitalization for HF. EBM was defined as treatment with β-blockers and renin angiotensin system inhibitors. The fraction of target dose (0-1) for each drug was calculated. The sum of the fractions gave each patient a score between 0 and 2. Patients were stratified into 4 groups according to this score: group 4 score = 2 (target dose of both drugs); group 3 score 1; group 2 score ≤1 to >0.5; and group 1 score ≤0.5. The risk of subsequent workforce detachment was estimated in cause specific Cox regression models.\ud \ud Results:\ud One year after first HF hospitalization, 10,185 patients were part of the workforce, and 7,561 (74%) were in treatment with at least 1 of the components of EBM. During a median follow-up of 727 days, 2,698 individuals (36%) became detached from the workforce. Patients receiving more EBM had a significantly lower risk of workforce detachment compared with those receiving less EBM (group 4 hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; group 3 HR: 0.85; 95% CI: 0.77 to 0.94; and group 2 HR 0.92; 95% CI: 0.83 to 1.02), all compared to group 1.\ud \ud Conclusions:\ud Patients in the workforce 1 year after first HF hospitalization and treated with target or near-target doses of EBM were associated with a significantly lower risk of subsequent workforce detachment.

OBJECTIVES: This study sought to assess safety and effectiveness of low-dose aspirin in heart failure (HF) not complicated by atrial fibrillation.BACKGROUND: Despite lack of evidence, low-dose aspirin is widely used in patients with HF and sinus rhythm with and without prior ischemic heart disease.METHODS: The study included 12,277 patients with new-onset HF during 2007 to 2012 who had no history of atrial fibrillation. Of 5,450 patients using low-dose aspirin at baseline, 3,840 were propensity matched to non-aspirin users in a 1:1 ratio. Propensity-matched Cox models were calculated with respect to the primary composite outcome of all-cause mortality, myocardial infarction, and stroke and the secondary outcomes of bleeding and HF readmission.RESULTS: The composite outcome occurred in 1,554 (40.5%) patients in the aspirin group and 1,604 (41.8%) patients in the non-aspirin group. Aspirin use was not associated with an altered risk of composite outcome (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.91 to 1.05), but it was associated with an increased risk of myocardial infarction (HR: 1.34; 95% CI: 1.08 to 1.67), whereas no differences were observed in all-cause mortality and stroke. An increased risk of HF readmission was observed in the aspirin group (HR: 1.25; 95% CI: 1.17 to 1.33). No difference in bleeding was observed. In subgroup analyses on the basis of a history of ischemic heart disease, the results were similar to the main result.CONCLUSIONS: No association was detected between low-dose aspirin use and the composite outcome of all-cause mortality, admission for myocardial infarction, and admission for stroke in patients with HF with no history of atrial fibrillation. Aspirin use was associated with an increased risk of readmission for HF.

Background—In patients with HF and preserved ejection fraction (HFpEF), little is known about the characteristics of and outcomes in those with and without diabetes. Methods—We examined clinical and echocardiographic characteristics and outcomes in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), according to history of diabetes. Cox regression models were used to estimate hazard ratios (HR) for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses. Results—Overall, 1134 of 4128 patients (27%) had diabetes. Compared to those without diabetes, they were more likely to have a history of myocardial infarction (28% vs. 22%), higher BMI (31kg/m2 vs. 29kg/m2), worse Minnesota living with HF score (48 vs. 40), higher median NT-proBNP concentration (403 vs 320 pg/ml; all pConclusions—In HFpEF, patients with diabetes have more signs of congestion, worse quality of life, higher NT-proBNP levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes on outcomes in HFPEF, and whether they are modifiable.

Background: Return to work is important financially, as a marker of functional status and for self-esteem in patients developing chronic illness. We examined return to work after first heart failure (HF) hospitalization.\ud Methods: By individual-level linkage of nationwide Danish registries, we identified 21455 patients of working age (18-60 years) with a first HF hospitalization in the period of 1997-2012. Of these 11880 (55%) were in the workforce prior to HF hospitalization and comprised the study population. We applied logistic regression to estimate odds ratios (OR) for associations between age, sex, length of hospital stay, level of education, income, comorbidity and return to work. \ud Results: One year after first HF hospitalization, 8040 (67.7%) returned to the workforce, 2981 (25.1%) did not, 805 (6.7%) died and 54 (0.5%) emigrated. Predictors of return to work included younger age (18-30 vs. 51-60 years, OR 3.12; 95% CI 2.42-4.03), male sex (OR 1.22 [1.18-1.34]) and level of education (long-higher vs. basic school OR 2.06 [1.63-2.60]). Conversely, hospital stay >7 days (OR 0.56 [0.51-0.62]) and comorbidity including history of stroke (OR 0.55 [0.45-0.69]), chronic kidney disease (OR 0.46 [0.36-0.59]), chronic obstructive pulmonary disease (OR 0.62 [0.52-0.75]), diabetes (OR 0.76 [0.68-0.85]) and cancer (OR 0.49 [0.40-0.61]) were all significantly associated with lower chance of return to work.\ud Conclusions: Patients in the workforce prior to HF hospitalization had low mortality but high risk of detachment from the workforce one year later. Young age, male sex, and higher level of education were predictors of return to work.

Aims: To investigate the prognostic significance of hospitalization for worsening heart failure (WHF), myocardial infarction (MI), and stroke in patients with chronic heart failure (HF). Methods and results: We studied 5011 patients with HF and reduced EF (HF-REF) in the CORONA trial and 4128 patients with HF and preserved EF (HF-PEF) in the I-Preserve trial. Adjusted hazard ratios (HRs) for death were estimated for 0–30 days and ≥31 days after first post-randomization WHF, MI, or stroke used as a time-dependent variable, compared with patients with none of these events. In CORONA, 1616 patients (32%) had post-randomization first events (1223 WHF, 216 MI, 177 stroke), and the adjusted HR for mortality ≤30 days after an event was: WHF 7.21 [95% confidence interval (CI) 2.05–25.40], MI 23.08 (95% CI 6.44–82.71), and stroke 32.15 (95% CI 8.93–115.83). The HR for mortality at > 30 days was: WHF 3.62 (95% CI 3.11–4.21), MI 4.41 (95% CI 3.23–6.02), and stroke 3.19 (95% CI 2.21–4.61). In I-Preserve, 896 patients (22%) experienced a post-randomization event (638 WHF, 111 MI, 147 stroke). The HR for mortality ≤30 days was WHF 31.77 (95% CI 7.60–132.81), MI 154.77 (95% CI 34.21–700.17), and stroke 223.30 (95% CI 51.42–969.78); for > 30 days it was WHF 3.36 (95% CI 2.79–4.05), MI 3.29 (95% CI 2.14–5.06), and stroke 5.13 (95% CI 3.61–7.29). Conclusions: In patients with both HF-REF and HF-PEF, hospitalization for WHF was associated with high early and late mortality. The early relative risk of death was not as great as following MI or stroke, but the longer term relative risk of death was similar following all three types of event. Numerically, more deaths occurred following WHF because it was a much more common event.

OBJECTIVES: The aim of this study was to investigate the impact of atrial fibrillation (AF) and antithrombotic treatment on the prognosis in patients with heart failure (HF) as well as vascular disease.BACKGROUND: HF, vascular disease, and AF are pathophysiologically related, and understanding antithrombotic treatment for these conditions is crucial.METHODS: In hospitalized patients with HF and coexisting vascular disease (coronary artery disease or peripheral arterial disease) followed from 1997 to 2009, AF status was categorized as prevalent AF, incident AF, or no AF. Risk of thromboembolism (TE), myocardial infarction (MI), and serious bleeding was assessed by Cox regression models (hazard ratio [HR] with 95% confidence interval [CI]) with antithrombotic therapy and AF as time-dependent variables.RESULTS: A total of 37,464 patients were included (age, 74.5 ± 10.7 years; 36.3% females) with a mean follow-up of 3 years during which 20.7% were categorized as prevalent AF and 17.2% as incident AF. Compared with vitamin K antagonist (VKA) in prevalent AF, VKA plus antiplatelet was not associated with a decreased risk of TE (HR: 0.91; 95% CI: 0.73 to 1.12) or MI (HR: 1.11; 95% CI: 0.96 to 1.28), whereas bleeding risk was significantly increased (HR: 1.31; 95% CI: 1.09 to 1.57). Corresponding estimates for incident AF were HRs of 0.77 (95% CI: 0.56 to 1.06), 1.07 (95% CI: 0.89 to 1.28), and 2.71 (95% CI: 1.33 to 2.21) for TE, MI, and bleeding, respectively. In no AF patients, no statistical differences were seen between antithrombotic therapies in TE or MI risk, whereas bleeding risk was significantly increased for VKA with and without single-antiplatelet therapy.CONCLUSIONS: In AF patients with coexisting HF and vascular disease, adding single-antiplatelet therapy to VKA therapy is not associated with additional benefit in thromboembolic or coronary risk, but notably increased bleeding risk.