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AimsChronic obstructive pulmonary disease (COPD) and heart failure (HF) are prevalent comorbidities associated with significant morbidity/mortality. We assessed prevalence of, patient profiles and outcomes associated with COPD across the ejection fraction (EF) spectrum.MethodsHF patients enrolled in the Swedish HF registry between 2005 and 2021 were considered. Multivariable logistic regression models were fitted to assess patient characteristics independently associated with COPD and Cox regression models for investigating the associations between COPD and outcomes, that is, morbidity/mortality.ResultsAmong 97 904 HF patients, COPD prevalence was 13%, highest in HF with preserved EF [HFpEF: 16%, HF with mildly reduced EF (HFmrEF): 12%, HF with reduced EF (HFrEF): 11%]. Key patient characteristics independently associated with a diagnosis of COPD included higher EF, female sex, smoking, obstructive sleep disorder, peripheral artery disease, a lower educational level, more severe HF, more likely mineralocorticoid receptor antagonist and diuretic use but less likely use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin-receptor-neprilysin inhibitors (not in HFrEF), beta-blockers, HF device therapies, and follow-up in HF nurse-led clinics. COPD was independently associated with a 15% higher risk of cardiovascular (CV) death/HF hospitalization [hazard ratio: 1.15 (95% confidence interval: 1.11-1.18)], CV death, non-CV death, all-cause death and HF hospitalizations, regardless of EF.ConclusionsCOPD was present in every eight patient with HF, and more common with preserved EF. Patients with COPD had more severe HF, heavier comorbidity burden and worse morbidity/mortality regardless of EF. Our results call for improved diagnostic and management strategies in patients with HF and COPD., Funding Agencies|Swedish Heart and Lung Foundation

Aims We assessed eligibility for omecamtiv mecarbil (OM) in a real-world cohort with heart failure with reduced ejection fraction (HFrEF) according to the selection criteria of the GALACTIC-HF trial (trial scenario) and selected trials criteria more likely to impact real-world use (pragmatic scenario). Methods and results We included 31,015 patients with HFrEF lasting >= 3 months and registered in the Swedish HF registry between 2000-2021. Trial eligibility was calculated by applying all the GALACTIC-HF selection criteria. The pragmatic scenario considered only the New York Heart Association class, history of worsening HF, N-terminal pro-B-type natriuretic peptides (NT-proBNP), blood pressure and renal failure criteria defined as in the trial. Eligibility for OM in chronic HFrEF was 21% and 36% in the trial and pragmatic scenarios, respectively. Eligibility was higher in those with EF<30% (trial: 27%, pragmatic: 44%), in-patients (trial:30%, pragmatic:57%), severe HF (trial: 35%, pragmatic: 60%), NYHA class III-IV (trial: 26%, pragmatic: 45%), and NT-proBNP >= 5,000pg/mL (trial: 30%, pragmatic: 51%). The criteria that most limited eligibility were history of a recent worsening HF event (60% eligible in chronic HFrEF), elevated NT-proBNP (82% eligible), and deviating blood pressure (82% eligible). Overall, eligible patients were characterized by more severe HF and higher CV event-rates in both scenarios, and higher comorbidity burden in the pragmatic scenario. Conclusion Approximately 21% of real-world chronic HFrEF patients would be eligible for OM according to the GALACTIC-HF selection criteria, and 36% according to the criteria more likely to affect OM use in clinical practice. Criteria in both scenarios identified a patient-group with severe HF and high CV event-rates., Funding Agencies|Cytokinetics; Horizon Europe programme [101095479 -MoreEUROPA]; Swedish Heart and Lung Foundation [20220680]

Aims To assess the use and associations with outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in a real-world population with heart failure (HF) and type 2 diabetes mellitus (T2DM). Methods and results The Swedish HF Registry was linked with the National Diabetes Registry and other national registries. Independent predictors of GLP-1 RA use were assessed by multivariable logistic regressions and associations with outcomes were assessed by Cox regressions in a 1:1 propensity score-matched cohort. Of 8188 patients enrolled in 2017-21, 9% received a GLP-1 RA. Independent predictors of GLP-1 RA use were age <75 years, worse glycaemic control, impaired renal function, obesity, and reduced ejection fraction (EF). GLP-1 RA use was not significantly associated with a composite of HF hospitalization (HHF) or cardiovascular (CV) death regardless of EF, but was associated with a lower risk of major adverse CV events (CV death, non-fatal stroke/transient ischaemic attack, or myocardial infarction), and CV and all-cause death. In patients with body mass index >= 30 kg/m2, GLP-1 RA use was also associated with a lower risk of HHF/CV death and HHF alone. Conclusions In patients with HF and T2DM, GLP-1 RA use was independently associated with more severe T2DM, reduced EF, and obesity and was not associated with a higher risk of HHF/CV death but with longer survival and less major CV adverse events. An association with lower HHF/CV death and HHF was observed in obese patients. Our findings provide new insights into GLP-1 RA use and its safety in HF and T2DM., Funding Agencies|European Union's Horizon Europe Research and Innovation Actions [101095479]; Swedish Heart and Lung Foundation [20220680]

AimsThe aim of this analysis was to provide data on the overall comorbidity burden, both cardiovascular (CV) and non-CV, in a large real-world heart failure (HF) population across the ejection fraction (EF).Methods and resultsPatients with HF from the Swedish HF Registry between 2000 and 2021 were included. Of 91 463 patients (median age 76 years [interquartile range 67-82]), 98% had at least one among the 17 explored comorbidities (94% at least one CV and 85% at least one non-CV comorbidity). All comorbidities, except for coronary artery disease (CAD), were more frequent in HF with preserved EF (HFpEF). Patients with multiple comorbidities were older, more likely female, inpatients, with HFpEF, worse New York Heart Association class and higher N-terminal pro-B-type natriuretic peptide levels. In a multivariable Cox model, 12 comorbidities were independently associated with a higher risk of death from any cause. The highest risk was associated with dementia (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.45-1.65), chronic kidney disease (HR 1.37, 95% CI 1.34-1.41), chronic obstructive pulmonary disease (HR 1.32, 95% CI 1.28-1.35). Obesity was associated with a lower risk of all-cause death (HR 0.81, 95% CI 0.79-0.84). CAD and valvular heart disease were associated with a higher risk of all-cause and CV mortality, but not non-CV mortality, whereas cancer and musculo-skeletal disease increased the risk of non-CV mortality. A significant interaction with EF was observed for several comorbidities. Occurrence of CV and non-CV outcomes was related to the number of CV and non-CV comorbidities, respectively.ConclusionThe burden of both CV and non-CV comorbidities was high in HF regardless of EF, but overall higher in HFpEF. Multimorbidity was associated with a high risk of death with a different burden on CV or non-CV outcomes. Prevalence and outcome of cardiovascular and non-cardiovascular comorbidities and of multimorbidity among 91 463 patients from the Swedish H, Funding Agencies|Swedish Heart and Lung Foundation

AimsThe aim of this analysis was to provide data on the overall comorbidity burden, both cardiovascular (CV) and non-CV, in a large real-world heart failure (HF) population across the ejection fraction (EF).Methods and resultsPatients with HF from the Swedish HF Registry between 2000 and 2021 were included. Of 91 463 patients (median age 76 years [interquartile range 67-82]), 98% had at least one among the 17 explored comorbidities (94% at least one CV and 85% at least one non-CV comorbidity). All comorbidities, except for coronary artery disease (CAD), were more frequent in HF with preserved EF (HFpEF). Patients with multiple comorbidities were older, more likely female, inpatients, with HFpEF, worse New York Heart Association class and higher N-terminal pro-B-type natriuretic peptide levels. In a multivariable Cox model, 12 comorbidities were independently associated with a higher risk of death from any cause. The highest risk was associated with dementia (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.45-1.65), chronic kidney disease (HR 1.37, 95% CI 1.34-1.41), chronic obstructive pulmonary disease (HR 1.32, 95% CI 1.28-1.35). Obesity was associated with a lower risk of all-cause death (HR 0.81, 95% CI 0.79-0.84). CAD and valvular heart disease were associated with a higher risk of all-cause and CV mortality, but not non-CV mortality, whereas cancer and musculo-skeletal disease increased the risk of non-CV mortality. A significant interaction with EF was observed for several comorbidities. Occurrence of CV and non-CV outcomes was related to the number of CV and non-CV comorbidities, respectively.ConclusionThe burden of both CV and non-CV comorbidities was high in HF regardless of EF, but overall higher in HFpEF. Multimorbidity was associated with a high risk of death with a different burden on CV or non-CV outcomes. Prevalence and outcome of cardiovascular and non-cardiovascular comorbidities and of multimorbidity among 91 463 patients from the Swedish H, Funding Agencies|Swedish Heart and Lung Foundation

AimsThe aim of this analysis was to provide data on the overall comorbidity burden, both cardiovascular (CV) and non-CV, in a large real-world heart failure (HF) population across the ejection fraction (EF).Methods and resultsPatients with HF from the Swedish HF Registry between 2000 and 2021 were included. Of 91 463 patients (median age 76 years [interquartile range 67-82]), 98% had at least one among the 17 explored comorbidities (94% at least one CV and 85% at least one non-CV comorbidity). All comorbidities, except for coronary artery disease (CAD), were more frequent in HF with preserved EF (HFpEF). Patients with multiple comorbidities were older, more likely female, inpatients, with HFpEF, worse New York Heart Association class and higher N-terminal pro-B-type natriuretic peptide levels. In a multivariable Cox model, 12 comorbidities were independently associated with a higher risk of death from any cause. The highest risk was associated with dementia (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.45-1.65), chronic kidney disease (HR 1.37, 95% CI 1.34-1.41), chronic obstructive pulmonary disease (HR 1.32, 95% CI 1.28-1.35). Obesity was associated with a lower risk of all-cause death (HR 0.81, 95% CI 0.79-0.84). CAD and valvular heart disease were associated with a higher risk of all-cause and CV mortality, but not non-CV mortality, whereas cancer and musculo-skeletal disease increased the risk of non-CV mortality. A significant interaction with EF was observed for several comorbidities. Occurrence of CV and non-CV outcomes was related to the number of CV and non-CV comorbidities, respectively.ConclusionThe burden of both CV and non-CV comorbidities was high in HF regardless of EF, but overall higher in HFpEF. Multimorbidity was associated with a high risk of death with a different burden on CV or non-CV outcomes. Prevalence and outcome of cardiovascular and non-cardiovascular comorbidities and of multimorbidity among 91 463 patients from the Swedish H, Funding Agencies|Swedish Heart and Lung Foundation

Aim We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration >= 6months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

Aims To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline-directed medical HF therapy (GDMT) and consequent outcomes.Methods and results Among patients in the Swedish HF registry with an ejection fraction <50% enrolled in 2009-2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1-4.0 vs. 1.4-1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1-44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin-angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors or beta-blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists.Conclusions Following a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re-/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re-/initiation of GDMT following a HF hospitalization., Funding Agencies|Abbott; Swedish Heart and Lung Foundation; Abbott Vascular; Bayer; Pharmacosmos; [20220680]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient s profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles Methods and results Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30- 60 or =60 ml/min/1.73m(2), sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30- 60ml/min/1.73m(2) and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR < 30 ml/min/1.73m(2) and AF. The three profiles with eGFR 30- 60ml/min/1.73m(2) also showed sBP < 90 mmHg Conclusions In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up., Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline-directed medical HF therapy (GDMT) and consequent outcomes.Methods and results Among patients in the Swedish HF registry with an ejection fraction <50% enrolled in 2009-2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1-4.0 vs. 1.4-1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1-44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin-angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors or beta-blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists.Conclusions Following a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re-/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re-/initiation of GDMT following a HF hospitalization., Funding Agencies|Abbott; Swedish Heart and Lung Foundation; Abbott Vascular; Bayer; Pharmacosmos; [20220680]

Aim We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration >= 6months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient s profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles Methods and results Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30- 60 or =60 ml/min/1.73m(2), sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30- 60ml/min/1.73m(2) and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR < 30 ml/min/1.73m(2) and AF. The three profiles with eGFR 30- 60ml/min/1.73m(2) also showed sBP < 90 mmHg Conclusions In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up., Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline-directed medical HF therapy (GDMT) and consequent outcomes.Methods and results Among patients in the Swedish HF registry with an ejection fraction <50% enrolled in 2009-2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1-4.0 vs. 1.4-1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1-44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin-angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors or beta-blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists.Conclusions Following a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re-/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re-/initiation of GDMT following a HF hospitalization., Funding Agencies|Abbott; Swedish Heart and Lung Foundation; Abbott Vascular; Bayer; Pharmacosmos; [20220680]

Aim We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration >= 6months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

Aims Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD.Methods and results We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or >= 60 ml/min/1.73 m(2), respectively. An eGFR >= 60 ml/min/1.73 m(2) and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD.Conclusions The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum., Funding Agencies|We thank all staff members at all care units in Sweden for their contribution to the SwedeHF.

Aims Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD.Methods and results We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or >= 60 ml/min/1.73 m(2), respectively. An eGFR >= 60 ml/min/1.73 m(2) and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD.Conclusions The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum., Funding Agencies|We thank all staff members at all care units in Sweden for their contribution to the SwedeHF.

Aims Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD.Methods and results We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or >= 60 ml/min/1.73 m(2), respectively. An eGFR >= 60 ml/min/1.73 m(2) and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD.Conclusions The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum., Funding Agencies|We thank all staff members at all care units in Sweden for their contribution to the SwedeHF.

Aims To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index >= 30 kg/m(2)) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. Conclusion Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk., Funding Agencies|Horizon Europe programme [101095479-More-EUROPA]; Swedish Heart and Lung Foundation [20220680]

Aims To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index >= 30 kg/m(2)) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. Conclusion Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk., Funding Agencies|Horizon Europe programme [101095479-More-EUROPA]; Swedish Heart and Lung Foundation [20220680]

Aims To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index >= 30 kg/m(2)) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. Conclusion Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk., Funding Agencies|Horizon Europe programme [101095479-More-EUROPA]; Swedish Heart and Lung Foundation [20220680]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient s profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles Methods and results Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30- 60 or =60 ml/min/1.73m(2), sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30- 60ml/min/1.73m(2) and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR < 30 ml/min/1.73m(2) and AF. The three profiles with eGFR 30- 60ml/min/1.73m(2) also showed sBP < 90 mmHg Conclusions In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up., Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient s profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles Methods and results Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30- 60 or =60 ml/min/1.73m(2), sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30- 60ml/min/1.73m(2) and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR < 30 ml/min/1.73m(2) and AF. The three profiles with eGFR 30- 60ml/min/1.73m(2) also showed sBP < 90 mmHg Conclusions In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up., Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD.Methods and results We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or >= 60 ml/min/1.73 m(2), respectively. An eGFR >= 60 ml/min/1.73 m(2) and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD.Conclusions The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum., Funding Agencies|We thank all staff members at all care units in Sweden for their contribution to the SwedeHF.

Aim We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration >= 6months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

Aims To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline-directed medical HF therapy (GDMT) and consequent outcomes.Methods and results Among patients in the Swedish HF registry with an ejection fraction <50% enrolled in 2009-2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1-4.0 vs. 1.4-1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1-44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin-angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors or beta-blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists.Conclusions Following a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re-/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re-/initiation of GDMT following a HF hospitalization., Funding Agencies|Abbott; Swedish Heart and Lung Foundation; Abbott Vascular; Bayer; Pharmacosmos; [20220680]

Aims The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline-directed medical treatments according to patient s profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles Methods and results Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30- 60 or =60 ml/min/1.73m(2), sBP 90-140mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30- 60ml/min/1.73m(2) and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR < 30 ml/min/1.73m(2) and AF. The three profiles with eGFR 30- 60ml/min/1.73m(2) also showed sBP < 90 mmHg Conclusions In a real-world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile-tailored approaches to guide drug implementation and follow-up., Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF).Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m(2) and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus =60 ml/min/1.73 m(2), from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus =6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow-up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively.Conclusions: Use of SGLT2i increased three-fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient, Funding Agencies|Swedish Heart and Lung Foundation; [20220680]

Aims To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index >= 30 kg/m(2)) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. Conclusion Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk., Funding Agencies|Horizon Europe programme [101095479-More-EUROPA]; Swedish Heart and Lung Foundation [20220680]

Aims To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index >= 30 kg/m(2)) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. Conclusion Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk., Funding Agencies|Horizon Europe programme [101095479-More-EUROPA]; Swedish Heart and Lung Foundation [20220680]

Aims Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD.Methods and results We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or >= 60 ml/min/1.73 m(2), respectively. An eGFR >= 60 ml/min/1.73 m(2) and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD.Conclusions The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum., Funding Agencies|We thank all staff members at all care units in Sweden for their contribution to the SwedeHF.

Aims To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline-directed medical HF therapy (GDMT) and consequent outcomes.Methods and results Among patients in the Swedish HF registry with an ejection fraction <50% enrolled in 2009-2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1-4.0 vs. 1.4-1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1-44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin-angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors or beta-blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists.Conclusions Following a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re-/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re-/initiation of GDMT following a HF hospitalization., Funding Agencies|Abbott; Swedish Heart and Lung Foundation; Abbott Vascular; Bayer; Pharmacosmos; [20220680]

Aim We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration >= 6months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality. [GRAPHICS] ., Funding Agencies|Bayer; Horizon Europe programme [101095479]; Swedish Heart and Lung Foundation [20220680]

Aims Digoxin is included in some heart failure (HF) guidelines but controversy persists about the true role for and impact of treatment with this drug, particularly in the absence of atrial fibrillation (AF). The aim of this study was to assess the association between clinical characteristics and digoxin use and between digoxin use and mortality/morbidity in a large, contemporary cohort of patients with HF with reduced ejection fraction (HFrEF) stratified by history of AF. Methods and results Patients with HFrEF (EF < 40%) enrolled in the Swedish HF registry between 2005 and 2018 were analysed. The independent association between digoxin use and patient characteristics was assessed by logistic regression, and between digoxin use and outcomes [composite of all-cause mortality or HF hospitalization (HFH), all-cause mortality, and HFH] by Cox regressions in a 1:1 propensity score matched population. Digoxin use was analysed at baseline and as a time-dependent variable. Of 42 456 patients with HFrEF, 16% received digoxin, 29% in the AF group and 2.8% in the non-AF group. The main independent predictors of use were advanced HF, higher heart rate, history of AF, preserved renal function, and concomitant use of beta blockers. Digoxin use was associated with lower risk of all-cause death/HFH [hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.91-0.99] in AF, but with higher risk in non-AF (HR: 1.24; 95% CI: 1.09-1.43). Consistent results were observed when digoxin use was analysed as a time-dependent variable. Conclusion The great majority of digoxin users had a history of AF. Digoxin use was associated with lower mortality/morbidity in patients with AF, but with higher mortality/morbidity in patients without AF.

Aims Digoxin is included in some heart failure (HF) guidelines but controversy persists about the true role for and impact of treatment with this drug, particularly in the absence of atrial fibrillation (AF). The aim of this study was to assess the association between clinical characteristics and digoxin use and between digoxin use and mortality/morbidity in a large, contemporary cohort of patients with HF with reduced ejection fraction (HFrEF) stratified by history of AF. Methods and results Patients with HFrEF (EF < 40%) enrolled in the Swedish HF registry between 2005 and 2018 were analysed. The independent association between digoxin use and patient characteristics was assessed by logistic regression, and between digoxin use and outcomes [composite of all-cause mortality or HF hospitalization (HFH), all-cause mortality, and HFH] by Cox regressions in a 1:1 propensity score matched population. Digoxin use was analysed at baseline and as a time-dependent variable. Of 42 456 patients with HFrEF, 16% received digoxin, 29% in the AF group and 2.8% in the non-AF group. The main independent predictors of use were advanced HF, higher heart rate, history of AF, preserved renal function, and concomitant use of beta blockers. Digoxin use was associated with lower risk of all-cause death/HFH [hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.91-0.99] in AF, but with higher risk in non-AF (HR: 1.24; 95% CI: 1.09-1.43). Consistent results were observed when digoxin use was analysed as a time-dependent variable. Conclusion The great majority of digoxin users had a history of AF. Digoxin use was associated with lower mortality/morbidity in patients with AF, but with higher mortality/morbidity in patients without AF.

Aims Digoxin is included in some heart failure (HF) guidelines but controversy persists about the true role for and impact of treatment with this drug, particularly in the absence of atrial fibrillation (AF). The aim of this study was to assess the association between clinical characteristics and digoxin use and between digoxin use and mortality/morbidity in a large, contemporary cohort of patients with HF with reduced ejection fraction (HFrEF) stratified by history of AF. Methods and results Patients with HFrEF (EF < 40%) enrolled in the Swedish HF registry between 2005 and 2018 were analysed. The independent association between digoxin use and patient characteristics was assessed by logistic regression, and between digoxin use and outcomes [composite of all-cause mortality or HF hospitalization (HFH), all-cause mortality, and HFH] by Cox regressions in a 1:1 propensity score matched population. Digoxin use was analysed at baseline and as a time-dependent variable. Of 42 456 patients with HFrEF, 16% received digoxin, 29% in the AF group and 2.8% in the non-AF group. The main independent predictors of use were advanced HF, higher heart rate, history of AF, preserved renal function, and concomitant use of beta blockers. Digoxin use was associated with lower risk of all-cause death/HFH [hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.91-0.99] in AF, but with higher risk in non-AF (HR: 1.24; 95% CI: 1.09-1.43). Consistent results were observed when digoxin use was analysed as a time-dependent variable. Conclusion The great majority of digoxin users had a history of AF. Digoxin use was associated with lower mortality/morbidity in patients with AF, but with higher mortality/morbidity in patients without AF.

Aims To assess the association between combination, dose and use of current guideline-recommended target doses (TD) of renin-angiotensin system inhibitors (RASi), angiotensin receptor-neprilysin inhibitors (ARNi) and beta-blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction. Methods and results Overall, 17 809 outpatients registered in the Swedish Heart Failure Registry (SwedeHF) from May 2000 to December 2018, with ejection fraction <40% and duration of HF >= 90 days were selected. Primary outcome was a composite of time to cardiovascular death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.83 (0.76-0.91) with <50% of TD, 0.78 (0.71-0.86) with 50%-99%, and 0.73 (0.67-0.80) with >= 100% of TD. Compared with no use of beta-blockers, the adjusted HR (95% CI) was 0.86 (0.76-0.91), 0.81 (0.74-0.89) and 0.74 (0.68-0.82) with <50%, 50%-99% and >= 100% of TD, respectively. Patients receiving both an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/ARNi and a beta-blocker at 50%-99% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi/ARB/ARNi or beta-blocker, even if this was at >= 100% of TD. Conclusion Heart failure with reduced ejection fraction patients using higher doses of RASi or ARNi and beta-blockers had lower risk of cardiovascular death or HF hospitalization. Use of two drug classes at 50%-99% of TD dose was associated with lower risk than one drug class at 100% of TD., Funding Agencies|EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]

Aims To assess the association between combination, dose and use of current guideline-recommended target doses (TD) of renin-angiotensin system inhibitors (RASi), angiotensin receptor-neprilysin inhibitors (ARNi) and beta-blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction. Methods and results Overall, 17 809 outpatients registered in the Swedish Heart Failure Registry (SwedeHF) from May 2000 to December 2018, with ejection fraction <40% and duration of HF >= 90 days were selected. Primary outcome was a composite of time to cardiovascular death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.83 (0.76-0.91) with <50% of TD, 0.78 (0.71-0.86) with 50%-99%, and 0.73 (0.67-0.80) with >= 100% of TD. Compared with no use of beta-blockers, the adjusted HR (95% CI) was 0.86 (0.76-0.91), 0.81 (0.74-0.89) and 0.74 (0.68-0.82) with <50%, 50%-99% and >= 100% of TD, respectively. Patients receiving both an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/ARNi and a beta-blocker at 50%-99% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi/ARB/ARNi or beta-blocker, even if this was at >= 100% of TD. Conclusion Heart failure with reduced ejection fraction patients using higher doses of RASi or ARNi and beta-blockers had lower risk of cardiovascular death or HF hospitalization. Use of two drug classes at 50%-99% of TD dose was associated with lower risk than one drug class at 100% of TD., Funding Agencies|EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]

Aims Digoxin is included in some heart failure (HF) guidelines but controversy persists about the true role for and impact of treatment with this drug, particularly in the absence of atrial fibrillation (AF). The aim of this study was to assess the association between clinical characteristics and digoxin use and between digoxin use and mortality/morbidity in a large, contemporary cohort of patients with HF with reduced ejection fraction (HFrEF) stratified by history of AF. Methods and results Patients with HFrEF (EF < 40%) enrolled in the Swedish HF registry between 2005 and 2018 were analysed. The independent association between digoxin use and patient characteristics was assessed by logistic regression, and between digoxin use and outcomes [composite of all-cause mortality or HF hospitalization (HFH), all-cause mortality, and HFH] by Cox regressions in a 1:1 propensity score matched population. Digoxin use was analysed at baseline and as a time-dependent variable. Of 42 456 patients with HFrEF, 16% received digoxin, 29% in the AF group and 2.8% in the non-AF group. The main independent predictors of use were advanced HF, higher heart rate, history of AF, preserved renal function, and concomitant use of beta blockers. Digoxin use was associated with lower risk of all-cause death/HFH [hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.91-0.99] in AF, but with higher risk in non-AF (HR: 1.24; 95% CI: 1.09-1.43). Consistent results were observed when digoxin use was analysed as a time-dependent variable. Conclusion The great majority of digoxin users had a history of AF. Digoxin use was associated with lower mortality/morbidity in patients with AF, but with higher mortality/morbidity in patients without AF.

Aims To assess the association between combination, dose and use of current guideline-recommended target doses (TD) of renin-angiotensin system inhibitors (RASi), angiotensin receptor-neprilysin inhibitors (ARNi) and beta-blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction. Methods and results Overall, 17 809 outpatients registered in the Swedish Heart Failure Registry (SwedeHF) from May 2000 to December 2018, with ejection fraction <40% and duration of HF >= 90 days were selected. Primary outcome was a composite of time to cardiovascular death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.83 (0.76-0.91) with <50% of TD, 0.78 (0.71-0.86) with 50%-99%, and 0.73 (0.67-0.80) with >= 100% of TD. Compared with no use of beta-blockers, the adjusted HR (95% CI) was 0.86 (0.76-0.91), 0.81 (0.74-0.89) and 0.74 (0.68-0.82) with <50%, 50%-99% and >= 100% of TD, respectively. Patients receiving both an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/ARNi and a beta-blocker at 50%-99% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi/ARB/ARNi or beta-blocker, even if this was at >= 100% of TD. Conclusion Heart failure with reduced ejection fraction patients using higher doses of RASi or ARNi and beta-blockers had lower risk of cardiovascular death or HF hospitalization. Use of two drug classes at 50%-99% of TD dose was associated with lower risk than one drug class at 100% of TD., Funding Agencies|EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]

Aims Digoxin is included in some heart failure (HF) guidelines but controversy persists about the true role for and impact of treatment with this drug, particularly in the absence of atrial fibrillation (AF). The aim of this study was to assess the association between clinical characteristics and digoxin use and between digoxin use and mortality/morbidity in a large, contemporary cohort of patients with HF with reduced ejection fraction (HFrEF) stratified by history of AF. Methods and results Patients with HFrEF (EF < 40%) enrolled in the Swedish HF registry between 2005 and 2018 were analysed. The independent association between digoxin use and patient characteristics was assessed by logistic regression, and between digoxin use and outcomes [composite of all-cause mortality or HF hospitalization (HFH), all-cause mortality, and HFH] by Cox regressions in a 1:1 propensity score matched population. Digoxin use was analysed at baseline and as a time-dependent variable. Of 42 456 patients with HFrEF, 16% received digoxin, 29% in the AF group and 2.8% in the non-AF group. The main independent predictors of use were advanced HF, higher heart rate, history of AF, preserved renal function, and concomitant use of beta blockers. Digoxin use was associated with lower risk of all-cause death/HFH [hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.91-0.99] in AF, but with higher risk in non-AF (HR: 1.24; 95% CI: 1.09-1.43). Consistent results were observed when digoxin use was analysed as a time-dependent variable. Conclusion The great majority of digoxin users had a history of AF. Digoxin use was associated with lower mortality/morbidity in patients with AF, but with higher mortality/morbidity in patients without AF.

Aims Digoxin is included in some heart failure (HF) guidelines but controversy persists about the true role for and impact of treatment with this drug, particularly in the absence of atrial fibrillation (AF). The aim of this study was to assess the association between clinical characteristics and digoxin use and between digoxin use and mortality/morbidity in a large, contemporary cohort of patients with HF with reduced ejection fraction (HFrEF) stratified by history of AF. Methods and results Patients with HFrEF (EF < 40%) enrolled in the Swedish HF registry between 2005 and 2018 were analysed. The independent association between digoxin use and patient characteristics was assessed by logistic regression, and between digoxin use and outcomes [composite of all-cause mortality or HF hospitalization (HFH), all-cause mortality, and HFH] by Cox regressions in a 1:1 propensity score matched population. Digoxin use was analysed at baseline and as a time-dependent variable. Of 42 456 patients with HFrEF, 16% received digoxin, 29% in the AF group and 2.8% in the non-AF group. The main independent predictors of use were advanced HF, higher heart rate, history of AF, preserved renal function, and concomitant use of beta blockers. Digoxin use was associated with lower risk of all-cause death/HFH [hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.91-0.99] in AF, but with higher risk in non-AF (HR: 1.24; 95% CI: 1.09-1.43). Consistent results were observed when digoxin use was analysed as a time-dependent variable. Conclusion The great majority of digoxin users had a history of AF. Digoxin use was associated with lower mortality/morbidity in patients with AF, but with higher mortality/morbidity in patients without AF.

Aims To assess the association between combination, dose and use of current guideline-recommended target doses (TD) of renin-angiotensin system inhibitors (RASi), angiotensin receptor-neprilysin inhibitors (ARNi) and beta-blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction. Methods and results Overall, 17 809 outpatients registered in the Swedish Heart Failure Registry (SwedeHF) from May 2000 to December 2018, with ejection fraction <40% and duration of HF >= 90 days were selected. Primary outcome was a composite of time to cardiovascular death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.83 (0.76-0.91) with <50% of TD, 0.78 (0.71-0.86) with 50%-99%, and 0.73 (0.67-0.80) with >= 100% of TD. Compared with no use of beta-blockers, the adjusted HR (95% CI) was 0.86 (0.76-0.91), 0.81 (0.74-0.89) and 0.74 (0.68-0.82) with <50%, 50%-99% and >= 100% of TD, respectively. Patients receiving both an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/ARNi and a beta-blocker at 50%-99% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi/ARB/ARNi or beta-blocker, even if this was at >= 100% of TD. Conclusion Heart failure with reduced ejection fraction patients using higher doses of RASi or ARNi and beta-blockers had lower risk of cardiovascular death or HF hospitalization. Use of two drug classes at 50%-99% of TD dose was associated with lower risk than one drug class at 100% of TD., Funding Agencies|EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]

Aims To assess the association between combination, dose and use of current guideline-recommended target doses (TD) of renin-angiotensin system inhibitors (RASi), angiotensin receptor-neprilysin inhibitors (ARNi) and beta-blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction. Methods and results Overall, 17 809 outpatients registered in the Swedish Heart Failure Registry (SwedeHF) from May 2000 to December 2018, with ejection fraction <40% and duration of HF >= 90 days were selected. Primary outcome was a composite of time to cardiovascular death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.83 (0.76-0.91) with <50% of TD, 0.78 (0.71-0.86) with 50%-99%, and 0.73 (0.67-0.80) with >= 100% of TD. Compared with no use of beta-blockers, the adjusted HR (95% CI) was 0.86 (0.76-0.91), 0.81 (0.74-0.89) and 0.74 (0.68-0.82) with <50%, 50%-99% and >= 100% of TD, respectively. Patients receiving both an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/ARNi and a beta-blocker at 50%-99% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi/ARB/ARNi or beta-blocker, even if this was at >= 100% of TD. Conclusion Heart failure with reduced ejection fraction patients using higher doses of RASi or ARNi and beta-blockers had lower risk of cardiovascular death or HF hospitalization. Use of two drug classes at 50%-99% of TD dose was associated with lower risk than one drug class at 100% of TD., Funding Agencies|EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]

Aims Iron deficiency (ID) is associated with poor prognosis regardless of anaemia. Intravenous iron improves quality of life and outcomes in patients with ID and heart failure (HF) with reduced ejection fraction (HFrEF). In the Swedish HF registry, we assessed (i) frequency and predictors of ID testing; (ii) prevalence and outcomes of ID with/without anaemia; (iii) use of ferric carboxymaltose (FCM) and its predictors in patients with ID. Methods and results We used multivariable logistic regressions to assess patient characteristics independently associated with ID testing/FCM use, and Cox regressions to assess risk of outcomes associated with ID. Of 21 496 patients with HF and any ejection fraction enrolled in 2017-2018, ID testing was performed in 27%. Of these, 49% had ID and more specifically 36% had ID-/anaemia-, 15% ID-/anaemia+, 29% ID+/anaemia-, and 20% ID+/anaemia+ (48%, 39%, 13%, 30% and 18% in HFrEF, respectively). Risk of recurrent all-cause hospitalizations was higher in patients with ID regardless of anaemia. Of 1959 patients with ID, 19% received FCM (24% in HFrEF). Important independent predictors of ID testing and FCM use were anaemia, higher New York Heart Association class, having HFrEF, and referral to HF specialty care. Conclusion In this nationwide HF registry, ID testing occurred in only about a quarter of the patients. Among tested patients, ID was present in one half, but only one in five patients received FCM indicating low adherence to current guidelines on screening and treatment., Funding Agencies|Vifor Pharma

Aims Iron deficiency (ID) is associated with poor prognosis regardless of anaemia. Intravenous iron improves quality of life and outcomes in patients with ID and heart failure (HF) with reduced ejection fraction (HFrEF). In the Swedish HF registry, we assessed (i) frequency and predictors of ID testing; (ii) prevalence and outcomes of ID with/without anaemia; (iii) use of ferric carboxymaltose (FCM) and its predictors in patients with ID. Methods and results We used multivariable logistic regressions to assess patient characteristics independently associated with ID testing/FCM use, and Cox regressions to assess risk of outcomes associated with ID. Of 21 496 patients with HF and any ejection fraction enrolled in 2017-2018, ID testing was performed in 27%. Of these, 49% had ID and more specifically 36% had ID-/anaemia-, 15% ID-/anaemia+, 29% ID+/anaemia-, and 20% ID+/anaemia+ (48%, 39%, 13%, 30% and 18% in HFrEF, respectively). Risk of recurrent all-cause hospitalizations was higher in patients with ID regardless of anaemia. Of 1959 patients with ID, 19% received FCM (24% in HFrEF). Important independent predictors of ID testing and FCM use were anaemia, higher New York Heart Association class, having HFrEF, and referral to HF specialty care. Conclusion In this nationwide HF registry, ID testing occurred in only about a quarter of the patients. Among tested patients, ID was present in one half, but only one in five patients received FCM indicating low adherence to current guidelines on screening and treatment., Funding Agencies|Vifor Pharma

Aims Use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in real-world heart failure (HF) is poorly characterised. In contemporary patients with HF and type 2 diabetes mellitus (T2DM) we assessed over time SGLT2i use, clinical characteristics and outcomes associated with SGLT2i use. Methods and results Type 2 diabetes patients enrolled in the Swedish HF Registry between 2016-2018 were considered. We performed multivariable logistic regression models to assess the independent predictors of SGLT2i use and Cox regression models in a 1:3 propensity score-matched cohort and relevant subgroups to investigate the association between SGLT2i use and outcomes. Of 6805 eligible HF patients with T2DM, 376 (5.5%) received SGLT2i, whose use increased over time with 12% of patients on treatment at the end of 2018. Independent predictors of SGLT2i use were younger age, HF specialty care, ischaemic heart disease, preserved kidney function, and absence of anaemia. Over a median follow-up of 256 days, SGLT2i use was associated with a 30% lower risk of cardiovascular (CV) death/first HF hospitalisation (hazard ratio 0.70, 95% confidence interval 0.52-0.95), which was consistent regardless of ejection fraction, background metformin treatment and kidney function. SGLT2i use was also associated with a lower risk of all-cause and CV death, HF and CV hospitalisation, and CV death/myocardial infarction/stroke. Conclusion In a contemporary HF cohort with T2DM, SGLT2i use increased over time, was more common with specialist care, younger age, ischaemic heart disease, and preserved renal function, and was associated with lower mortality and morbidity., Funding Agencies|AstraZenecaAstraZeneca; EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2019-01059]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation