Initiation of medical therapy for heart failure patients according to kidney function: a Danish nationwide study

Background: Use of medical therapies for heart failure (HF) patients with moderate kidney dysfunction is low. We hypothesized that lack of initiation of HF therapy reflects the clinicians’ reluctance in very elderly and frail patients more than kidney dysfunction itself. Methods: HF patients were identified from nationwide registers between 2014 and 2021. Information was obtained on eGFR, frailty status, and prescription of HF therapy. Patients were divided into three groups: normal kidney function (eGFR ≥ 60); moderate kidney dysfunction (GFR between 30 and 59); and severe kidney dysfunction (GFR < 30). Multivariate Cox models were used to study the association of eGFR, age, and frailty with use of HF therapy. Results: Of the 42,320 HF patients included those with lower eGFR were significantly older and frailer (median age 74.3 years and 37.8% frail). The crude initiation rate of all three drug classes decreased with decreasing eGFR in a stepwise fashion. After adjusting for age and frailty status, initiation of MRA decreased with decreasing kidney function (moderate kidney function HR 0.80(95% CI 0.77–0.84) and severe kidney function HR 0.24(0.21–0.27)). After adjusting for age and frailty status, initiation of RAS inhibitor and BB was not significantly lower for moderate kidney dysfunction (HR 0.97(0.93–1.02), and HR 1.06(0.97–1.16, respectively)). Initiation of RAS inhibitor was significantly lower for patients with severe kidney dysfunction, HR 0.45(0.41–0.50), but not for BB initiation HR 1.09(1.05–1.14). Conclusion: In a real-world HF cohort, patients with moderate and severe kidney dysfunction were associated with reduced use of MRA irrespective of age and frailty. Reduced use of RASi was associated with severe kidney dysfunction, whereas for patients with moderate kidney dysfunction, reduced use was mainly driven by aging and frailty. Reduced use of BB seemed to be primarily explained by aging and frailty

Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with type 2 diabetes and cardiovascular disease in Denmark: a cross-sectional, nationwide study

Background: Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease. Methods: For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist. Findings: Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7–6·1) and median age across the three frailty groups was 71 years (64–79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88–0·94, p<0·0001; severely frail 0·75, 0·70–0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity. Interpretation: In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority. Funding: Department of Cardiology, Herlev and Gentofte University Hospital. Translation: For the Danish translation of the abstract see Supplementary Materials section

Adherence and discontinuation of optimal heart failure therapies according to age: a Danish nationwide study

Background: Guideline‐recommended disease‐modifying pharmacological therapies for heart failure (HF) with reduced ejection fraction are underutilized, particularly among elderly patients. We studied the association of age in adherence and discontinuation of angiotensin‐converting enzyme inhibitors/angiotensin‐II receptor blockers (ACEi/ARB), β‐blockers (BB), and mineralocorticoid receptor antagonists. Methods and Results: Patients with a first heart failure diagnosis who had initiated ACEi/ARB and BB within 120 days of presentation were included from nationwide registries and divided into 3 age groups: <65 years (reference), 65 to 79, and ≥80. One‐year median proportions of daily target doses were calculated. Adherence was estimated by the proportion of days covered. The 5‐year risk of discontinuation was assessed with the Aalen‐Johansen estimator. Discontinuation rates were evaluated using Multivariable Cox regression. Twenty‐nine thousand four hundred eighty‐two patients were included. Advancing age was associated with lower median proportions of daily target doses and adherence (ACEi/ARB 79.1%, 77.5%, and 69.4%; BB 79.1%, 78.6%, and 73.8%), in the <65, 65 to 79, and ≥80 age groups, respectively. Age ≥80 was associated with higher discontinuation rates (cumulative incidence, ACEi/ARB 41%, 44%, and 51%; BB 38%, 35%, and 39%; hazard ratio, ACEi/ARB 1.60 [95% CI, 1.51–1.69]; BB 1.33 [95% CI, 1.25–1.41]). The risk of mineralocorticoid receptor antagonists discontinuation differed little with age (50%, 54%, and 56%), although mineralocorticoid receptor antagonists initiation in the most elderly was less frequent (33%, 33%, and 22%). Conclusions: In a nationwide cohort of patients with heart failure, advanced age was associated with lower proportions of daily target doses, lower adherence, and higher discontinuation rates of ACEi/ARB and BBs. Focus on treatment adherence and optimal dosages among elderly patients with heart failure could improve outcomes

Importance of diagnostic setting in determining mortality in patients with new-onset heart failure: temporal trends in Denmark 1997–2017

Aim: To investigate temporal trends in inpatient vs. outpatient diagnosis of new-onset heart failure (HF) and the subsequent risk of death and hospitalization. Methods and results: Using nationwide registers, 192 581 patients with a first diagnosis of HF (1997–2017) were included. We computed incidences of HF, age-standardized mortality rates, and absolute risks (ARs) of death and hospitalization (accounting for competing risk of death) to understand the importance of the diagnosis setting in relation to subsequent mortality and hospitalization. The overall incidence of HF was approximately the same (170/100 000 persons) every year during 1997–2017. However, in 1997, 77% of all first diagnoses of HF were made during a hospitalization, whereas the proportion was 39% in 2017. As inpatient diagnoses decreased, outpatient diagnoses increased from 23% to 61%. Outpatients had lower mortality and hospitalization rates than inpatients throughout the study period, although the 1-year age-standardized mortality rate decreased for each inpatient (24 to 14/100-person) and outpatient (11 to 7/100-person). One-year and five-year AR of death decreased by 11.1% and 17.0%, respectively, for all HF patients, while the risk of hospitalization for HF did not decrease significantly (1.13% and 0.96%, respectively). Conclusion: Between 1997 and 2017, HF changed from being primarily diagnosed during hospitalization to being mostly diagnosed in the outpatient setting. Outpatients had much lower mortality rates than inpatients throughout the study period. Despite a significant decrease in mortality risk for all HF patients, neither inpatients nor outpatients experienced a reduction in the risk of an HF hospitalization

Temporal trends in the initiation of dialysis among patients with heart failure with or without diabetes: a nationwide study from 2002 to 2016

Background The incidence and distribution of acute and chronic dialysis among patients with heart failure (HF), stratified by diabetes, remain uncertain. We hypothesized that with improved survival and rising comorbidities, the demand for dialysis would increase over time. Methods and Results Patients with incident HF, aged 18 to 100 years, between 2002 and 2016, were identified using Danish nationwide registers. Primary outcomes included acute and chronic dialysis initiation, HF‐related hospitalization, and all‐cause mortality. These outcomes were assessed in 2002 to 2006, 2007 to 2011, and 2012 to 2016, stratified by diabetes. We calculated incidence rates (IRs) per 1000 person‐years and hazard ratios (HR) using multivariable Cox regression. Of 115 533 patients with HF, 2734 patients received acute dialysis and 1193 patients received chronic dialysis. The IR was 8.0 per 1000 and 3.5 per 1000 person‐years for acute and chronic dialysis, respectively. Acute dialysis rates increased significantly among patients with diabetes over time, while no significant changes occurred in those without diabetes, chronic dialysis, HF‐related hospitalization, or overall mortality. Diabetes was associated with significantly higher HRs of acute and chronic dialysis, respectively, compared with patients without diabetes (HR, 2.07 [95% CI, 1.80–2.39] and 2.93 [95% CI, 2.40–3.58] in 2002 to 2006; HR, 2.45 [95% CI, 2.14–2.80] and 2.86 [95% CI, 2.32–3.52] in 2007 to 2011; and 2.69 [95% CI, 2.33–3.10] and 3.30 [95% CI, 2.69–4.06] in 2012 to 2016). Conclusions The IR of acute and chronic dialysis remained low compared with HF‐related hospitalizations and mortality. Acute dialysis rates increased significantly over time, contrasting no significant trends in other outcomes. Diabetes exhibited over 2‐fold increased rates of the outcomes. These findings emphasize the importance of continued monitoring and renal care in patients with HF, especially with diabetes, to optimize outcomes and prevent adverse events

Association between early detected heart failure stages and future cardiovascular and non-cardiovascular events in the elderly (Copenhagen Heart Failure Risk Study)

BACKGROUND: Early stages of heart failure (HF) are associated with an increased risk of hospitalization and increased mortality, however the course of progression and the impact of non-cardiovascular comorbidities on adverse events in elderly high-risk patients are unknown. AIM: To examine the risk of future cardiovascular (CV) and non-CV events in early stages of HF in a cohort of elderly patients (age ≥ 60 with ≥ 1 risk factor for HF and without known or clinically suspected HF). METHODS: A total of 400 patients (American Heart Association HF stage A: N = 177; stage B: N = 150; stage C: N = 73) from the Copenhagen Heart Failure Risk Study were identified and followed for the main composite outcome of a HF hospitalization (HFH), ischemic heart disease (IHD), stroke, and all-cause death, recorded within the Danish nationwide registries. Non-CV hospitalization was a secondary outcome. Absolute risk was calculated by the Aalen-Johansen estimator. RESULTS: The median follow-up time was 3.3 years, total number of events were 83, and the 3-year risk (95% confidence interval) of the main outcome was 12.8% (7.8–17.9), 22.8% (16.1–29.6) and 31.8% (21.0–42.6) for patients with stage A, B, and C, respectively. 1.1% (0.0–2.7), 3.4% (1.0–6.3) and 10.0% (2.8–16.3) experienced HFH as their first event, whereas 37.3% (30.2–44.4), 49.7% (41.6–57.8) and 54.8% (43.4–66.2) were admitted for non-CV causes as their first event. CONCLUSION: The risk of HFH, IHD, stroke and all-cause death increased with severity of HF stage, and 10% of patients with undiagnosed HF stage C were admitted for HF within 3 years. However, the risk of non-CV hospitalizations was greater compared to the risk of experiencing HFH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-022-02875-1

Temporal trends in initiation of mineralocorticoid receptor antagonists and risk of subsequent withdrawal in patients with heart failure: a nationwide study in Denmark from 2003–2017

Aims: Despite landmark heart failure (HF) with reduced ejection fraction (HFrEF) trials showing effect of mineralocorticoid receptor antagonists (MRA) on the risk of death and HF hospitalization, it has been suggested that MRAs are underutilized or frequently withdrawn. This study sought to identify temporal trends in the initiation of MRAs and the subsequent risk of withdrawal and adherence of MRAs in HF patients treated with a renin–angiotensin system inhibitor and a beta-blocker in Denmark from 2003–2017. Methods and results: From nationwide registries, we identified patients receiving a diagnosis of HF. Use of MRA was identified by at least one prescription within 6 months after the diagnosis. The absolute risk of withdrawal with treatment was assessed with cumulative incidence, accounting for the competing risk of death. To estimate adherence, we calculated the proportion of days covered. We included 51 512 patients with incident HF. During the study period, 20 779 (40.3%) patients initiated MRA therapy. The incidence of withdrawal of MRA was 49.2% throughout the study period; 48.0% of the HF patients were adherent to the treatment. Among patients withdrawing treatment with MRA, the cumulative incidence of reinitiating was 36.6%. Conclusions: In a nationwide cohort of patients with HF, approximately half of the patients received MRA as third-line therapy within the first 6 months after diagnosis and approximately half of these withdrew MRA within 5 years. These findings warrant an increasing focus on retention to MRA treatment in a real-life setting