Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 625
Filtrar
1.
Kidney Int Rep ; 7(1): 36-45, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35005312

RESUMO

Introduction: FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) investigated the nonsteroidal, selective mineralocorticoid receptor (MR) antagonist finerenone in patients with CKD and type 2 diabetes (T2D). This analysis explores the impact of use of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on the treatment effect of finerenone. Methods: Patients (N = 5674) with T2D, urine albumin-to-creatinine ratio (UACR) of 30 to 5000 mg/g and estimated glomerular filtration rate (eGFR) of 25 to <75 ml/min per 1.73 m2 receiving optimized renin-angiotensin system (RAS) blockade were randomized to finerenone or placebo. Endpoints were change in UACR and a composite kidney outcome (time to kidney failure, sustained decrease in eGFR ≥40% from baseline, or renal death) and key secondary cardiovascular outcomes (time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) (ClinicalTrials.gov, NCT02540993). Results: Of 5674 patients, 259 (4.6%) received an SGLT-2i at baseline. Reduction in UACR with finerenone was found with or without use of SGLT-2i at baseline, with ratio of least-squares means of 0.69 (95% CI = 0.66-0.71) and 0.75 (95% CI -= 0.62-0.90), respectively (P interaction = 0.31). Finerenone also significantly reduced the kidney and key secondary cardiovascular outcomes versus placebo; there was no clear difference in the results by SGLT-2i use at baseline (P interaction = 0.21 and 0.46, respectively) or at any time during the trial. Safety was balanced with or without SGLT-2i use at baseline, with fewer hyperkalemia events with finerenone in the SGLT-2i group (8.1% vs. 18.7% without). Conclusion: UACR improvement was observed with finerenone in patients with CKD and T2D already receiving SGLT-2is at baseline, and benefits on kidney and cardiovascular outcomes appear consistent irrespective of use of SGLT-2i.

2.
Eur J Heart Fail ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014132

RESUMO

In order to ensure that the next generation of heart failure specialists will receive high-quality training, this document outlines the new European training and certification requirements for physicians with an interest in heart failure and for those working in certified heart failure centres, required by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

3.
Diabetes Care ; 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35061867

RESUMO

OBJECTIVE: Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS: Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30-5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin-angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS: Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS: Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

4.
Eur J Heart Fail ; 2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35064730

RESUMO

BACKGROUND: Few prior studies have investigated differences in precipitants leading to hospitalisations for acute heart failure (AHF) in a cohort with global representation. METHODS: We analysed the prevalence of precipitants and their association with outcomes in 18,553 patients hospitalised for AHF in REPORT-HF (prospective international REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) according to left ventricular ejection fraction (LVEF) subtype (reduced [HFrEF] and preserved ejection fraction [HFpEF]) and presentation (new-onset vs. decompensated chronic HF [DCHF]). Patients were enrolled from 358 centres in 44 countries stratified according to Latin America, North America, western Europe, Eastern Europe, Eastern Mediterranean and Africa, Southeast Asia, and Western Pacific. Precipitants were pre-defined as mutually exclusive categories and selected according to the local investigators discretion. Outcomes included in-hospital and 1-year mortality. RESULTS: The median age was 67 (IQR 57-77) years, and 39% were women. Acute coronary syndrome (ACS) was the most common precipitant in patients with new-onset HF in all regions except for North America and Western Europe, where uncontrolled hypertension and arrhythmia were the most common precipitants, independent of HF subtype and other confounders. In patients with DCHF, non-adherence to diet/medication was the most common precipitant regardless of region. Uncontrolled hypertension was a more likely precipitant in HFpEF, non-adherence to diet/medication, and ACS were more likely precipitants in HFrEF. Patients admitted due to worsening renal function had the worst in-hospital (4%) and 1-year post-discharge (30%) mortality rates, regardless of region, HF subtype and admission type (Pinteraction >0.05 for all). CONCLUSION: Data on global differences in precipitants for AHF highlight potential regional differences in targets for preventing hospitalisation for AHF and identifying those at highest risk for early mortality.

6.
ESC Heart Fail ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35029056

RESUMO

AIMS: Recent trials have evaluated sodium-glucose co-transporter 2 inhibitors in patients with heart failure (HF). We sought to assess the robustness of findings from these trials using the fragility index (FI). METHODS AND RESULTS: Fragility index is defined as the minimum number of patients that must be moved from the 'non-event' to the 'event' group to turn a statistically significant result to non-significant. In addition to FI, fragility quotient [(FQ); FI divided by the sample size] was calculated to assess the proportion of events that must be moved to change the significance. For statistically non-significant outcomes, reverse fragility index (RFI) and reverse fragility quotient (RFQ) were calculated. Robustness of findings after pooling data from all three trials was also assessed. A robust reduction in first HF hospitalization or cardiovascular mortality was seen with dapagliflozin (FI = 62 and FQ = 0.013), empagliflozin (FI = 50 and FQ = 0.013), and sotagliflozin (FI = 60 and FQ = 0.049). Dapagliflozin nominally improved all-cause and cardiovascular mortality, with modest FI (n = 8 and 5) and FQ (0.002 and 0.001). Empagliflozin and sotagliflozin did not demonstrate statistically significant reductions in all-cause mortality, with modest RFI (empagliflozin: RFI = 26 and RFQ = 0.007; sotagliflozin: RFI = 6 and RFQ = 0.005). A similar trend was seen with cardiovascular mortality (empagliflozin: RFI = 24 and RFQ = 0.006; sotagliflozin: RFI = 7 and RFQ = 0.006). Upon meta-analysis, the result for first HF hospitalization or cardiovascular mortality was robust (FI = 95 and FQ = 0.010). The reductions in all-cause (FI = 12 and FQ = 0.001) and cardiovascular mortality (FI = 9 and FQ = 0.001), while statistically significant, were fragile. CONCLUSION: Improvement in the composite outcome of first HF hospitalization or cardiovascular death was highly concordant and robust across sodium-glucose co-transporter 2 inhibitor trials. In contrast, secondary endpoints of all-cause and cardiovascular mortality were statistically fragile, underscoring the need to power trials for mortality to fully understand the benefit of therapies on fatal events.

7.
Am Heart J ; 243: 11-14, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34516969

RESUMO

Important racial differences in characteristics, treatment, and outcomes of patients with acute heart failure (AHF) have been described. The objective of this analysis of the International Registry to assess medical Practice with longitudinal observation for Treatment of Heart Failure (REPORT-HF) registry was to investigate racial differences in patients with AHF according to country income level.

8.
Diabetes Obes Metab ; 24(1): 125-134, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34580995

RESUMO

AIMS: Finerenone significantly reduced the risk of kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease and type 2 diabetes in the FIDELIO-DKD trial (NCT02540993). This exploratory subgroup analysis investigates the effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) use on the treatment effect of finerenone. MATERIALS AND METHODS: Patients with type 2 diabetes, urine albumin-to-creatinine ratio (UACR) 30-5000 mg/g and estimated glomerular filtration rate 25-<75 ml/min per 1.73 m2 receiving optimized renin-angiotensin system blockade were randomized to finerenone or placebo. RESULTS: Of the 5674 patients analysed, overall, 394 (6.9%) received GLP-1RAs at baseline. A reduction in UACR with finerenone was observed with or without baseline GLP-1RA use; ratio of least-squares means 0.63 (95% confidence interval 0.56, 0.70) with GLP-1RA use and 0.69 (95% confidence interval 0.67, 0.72) without GLP-1RA use (p value for interaction .20). Finerenone also significantly reduced the primary kidney (time to kidney failure, sustained decrease in estimated glomerular filtration rate ≥40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) versus placebo, with no clear difference because of GLP-1RA use at baseline (p value for interaction .15 and .51 respectively) or any time during the trial. The safety profile of finerenone was similar between subgroups. CONCLUSIONS: This exploratory subgroup analysis suggests that finerenone reduces UACR in patients with or without GLP-1RA use at baseline, and the effects on kidney and CV outcomes are consistent irrespective of GLP-1RA use.

9.
Eur Heart J ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34878502

RESUMO

AIMS : No therapy has shown to reduce the risk of hospitalization for heart failure across the entire range of ejection fractions seen in clinical practice. We assessed the influence of ejection fraction on the effect of the sodium-glucose cotransporter 2 inhibitor empagliflozin on heart failure outcomes. METHODS AND RESULTS : A pooled analysis was performed on both the EMPEROR-Reduced and EMPEROR-Preserved trials (9718 patients; 4860 empagliflozin and 4858 placebo), and patients were grouped based on ejection fraction: <25% (n = 999), 25-34% (n = 2230), 35-44% (n = 1272), 45-54% (n = 2260), 55-64% (n = 2092), and ≥65% (n = 865). Outcomes assessed included (i) time to first hospitalization for heart failure or cardiovascular mortality, (ii) time to first heart failure hospitalization, (iii) total (first and recurrent) hospitalizations for heart failure, and (iv) health status assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). The risk of cardiovascular death and hospitalization for heart failure declined progressively as ejection fraction increased from <25% to ≥65%. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalization, mainly by reducing heart failure hospitalizations. Empagliflozin reduced the risk of heart failure hospitalization by ≈30% in all ejection fraction subgroups, with an attenuated effect in patients with an ejection fraction ≥65%. Hazard ratios and 95% confidence intervals were: ejection fraction <25%: 0.73 (0.55-0.96); ejection fraction 25-34%: 0.63 (0.50-0.78); ejection fraction 35-44%: 0.72 (0.52-0.98); ejection fraction 45-54%: 0.66 (0.50-0.86); ejection fraction 55-64%: 0.70 (0.53-0.92); and ejection fraction ≥65%: 1.05 (0.70-1.58). Other heart failure outcomes and measures, including KCCQ, showed a similar response pattern. Sex did not influence the responses to empagliflozin. CONCLUSION : The magnitude of the effect of empagliflozin on heart failure outcomes was clinically meaningful and similar in patients with ejection fractions <25% to <65%, but was attenuated in patients with an ejection fraction ≥65%. KEY QUESTION: How does ejection fraction influence the effects of empagliflozin in patients with heart failure and either a reduced or a preserved ejection fraction? KEY FINDING: The magnitude of the effect of empagliflozin on heart failure outcomes and health status was similar in patients with ejection fractions <25% to <65%, but it was attenuated in patients with an ejection fraction ≥65%. TAKE HOME MESSAGE: The consistency of the response in patients with ejection fractions of <25% to <65% distinguishes the effects of empagliflozin from other drugs that have been evaluated across the full spectrum of ejection fractions in patients with heart failure.

10.
Eur J Heart Fail ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34894038

RESUMO

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been recently recommended as a foundational therapy for patients with heart failure (HF) and reduced ejection fraction (HFrEF) because of their favourable effects on mortality, clinical events and quality of life. While clinical practice guidelines have recommended the use of dapagliflozin and empagliflozin regardless of diabetes history in patients with HFrEF, or sotagliflozin in those with HFrEF and concomitant type 2 diabetes mellitus (T2DM), the timing and practical integration of this class of therapies in practice is less well defined. We propose that these drugs are candidates for early, upfront administration to patients with newly diagnosed HFrEF and for patients hospitalized with HF. Growing evidence has established early benefits, with clinically meaningful reductions in clinical events that reach statistical significance within days to weeks, following dapagliflozin, empagliflozin or, in diabetic patients, sotagliflozin initiation. Secondly, although major clinical trials have tested these drugs in patients already receiving background HF therapy, secondary analyses showed that their efficacy is independent of that. Third, SGLT2 inhibitors are generally safe and well tolerated, with clinical trial data reporting minimal effects on blood pressure, glycaemia-related adverse events, and no excess in acute kidney injury. Rather, they exert renal protective effects and reduce risk of hyperkalaemia, properties that favour initiation, tolerance and persistence of renin-angiotensin-system inhibitors and mineralocorticoid receptor antagonists. This review, therefore, supports the early initiation of dapagliflozin and empagliflozin (or sotagliflozin limited to patients with T2DM) to rapidly improve clinical outcome and quality of life of HFrEF patients.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34861154

RESUMO

BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as ß blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; pinteraction=0·18). A similar result was seen for ß blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; pinteraction=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus ß blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; pinteraction=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34850173

RESUMO

BACKGROUND: The nonsteroidal mineralocorticoid receptor antagonist finerenone and the sodium-glucose co-transporter-2 inhibitor canagliflozin reduce cardiorenal risk in albuminuric patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). At first glance, the results of FIDELIO-DKD (ClinicalTrials.gov, NCT02540993) and CREDENCE appear disparate. In FIDELIO-DKD, the primary end-point had a 18% (95% CI 7% to 27%) relative risk reduction; in CREDENCE the primary end-point had a 30% (95% CI 18% to 41%) relative risk reduction. Unlike CREDENCE, FIDELIO-DKD trial included patients with high albuminuria but excluded patients with symptomatic heart failure with reduced ejection fraction. The primary end-point in the FIDELIO-DKD trial was kidney specific and included a sustained decline in eGFR of ≥40% from baseline. In contrast, the primary end-point in the CREDENCE trial was included a sustained decline in eGFR of ≥57% from baseline and cardiovascular death. This post-hoc exploratory analysis investigated how differences in trial design-inclusion/exclusion criteria and definition of primary outcomes- influenced observed treatment effects. METHODS: Patients from FIDELIO-DKD who met the CKD inclusion criteria of the CREDENCE study (urine albumin-to-creatinine ratio >300-5000 mg/g and an estimated glomerular filtration rate of 30-<90 ml/min/1.73 m2 at screening) were included in this analysis. The primary end point was a cardiorenal composite (cardiovascular death, kidney failure, estimated glomerular filtration rate decrease of ≥57% sustained for ≥4 weeks or renal death). Patients with symptomatic heart failure with reduced ejection fraction were excluded from FIDELIO-DKD. Therefore, in a sensitivity analysis, we further adjusted for the baseline prevalence of heart failure. RESULTS: Of 4619/5674 (81.4%) patients who met the subgroup inclusion criteria, 49.6% were treated with finerenone and 50.4% received placebo. The rate of the cardiorenal composite end point was 43.9/1000 patient years with finerenone compared to 59.5/1000 patient years with placebo. The relative risk was significantly reduced by 26% with finerenone versus placebo (hazard ratio 0.74, 95% CI 0.63-0.87).In CREDENCE, the rate of the cardiorenal composite end point was 43.2/1000 patient years with canagliflozin compared to 61.2/1000 patient years with placebo; a 30% risk reduction was observed with canagliflozin (hazard ratio 0.70, 95% CI 0.59-0.82). CONCLUSIONS: This analysis highlights the pitfalls of direct comparisons between trials. When key differences in trial design are considered, FIDELIO-DKD and CREDENCE demonstrate cardiorenal benefits of a similar magnitude.

14.
Eur J Heart Fail ; 2021 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-34957660

RESUMO

AIMS: Anaemia is frequent among patients with heart failure (HF) and reduced ejection fraction (HFrEF) and is associated with poor outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) increase haematocrit and may correct anaemia. This study aims to investigate the impact of empagliflozin on haematocrit and anaemia, and whether anaemia influenced the effect of empagliflozin in EMPEROR-Reduced. METHODS AND RESULTS: Mixed-effects models and survival analysis. A total of 3726 patients (out of 3730) had baseline haematocrit values, 3013 (81%) had no anaemia and 713 (19%) had anaemia. Patients with anaemia were older (70.4 vs. 66.0 years), had lower body mass index (26.6 vs. 28.2 kg/m2 ), lower estimated glomerular filtration rate (54.2 vs. 63.9 ml/min/1.73 m2 ), and higher N-terminal pro-B-type natriuretic peptide (2362 vs. 1800 pg/ml). Compared to patients without anaemia, those with anaemia had 1.5 to 2.5-fold higher rates of cardiovascular and all-cause mortality, total HF hospitalizations, and kidney composite outcomes. The effect of empagliflozin to reduce the primary composite outcome of cardiovascular death or HF hospitalizations, total HF hospitalizations, and kidney composite outcome was not modified by baseline anaemia status (interaction p > 0.1 for all). Compared to placebo, empagliflozin rapidly (as early as week 4) increased haematocrit and haemoglobin and reduced the rates of new-onset anaemia throughout the follow-up (22.6% in placebo vs. 12.3% in empagliflozin; hazard ratio 0.49, 95% confidence interval 0.41-0.59; p < 0.001). CONCLUSIONS: Anaemia was associated with poor outcomes. Empagliflozin reduced new-onset anaemia throughout the follow-up and improved HF and kidney outcomes irrespective of anaemia status at baseline.

15.
Eur J Heart Fail ; 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34969177

RESUMO

Genetic cardiomyopathies are disorders of the cardiac muscle, most often explained by pathogenic mutations in genes encoding sarcomere, cytoskeleton, or ion channel proteins. Clinical phenotypes such as heart failure and arrhythmia are classically treated with generic drugs, but aetiology-specific and targeted treatments are lacking. As a result, cardiomyopathies still present a major burden to society, and affect many young and older patients. The Translational Committee of the Heart Failure Association (HFA) and the Working Group of Myocardial Function of the European Society of Cardiology (ESC) organized a workshop to discuss recent advances in molecular and physiological studies of various forms of cardiomyopathies. The study of cardiomyopathies has intensified after several new study setups became available, such as induced pluripotent stem cells, three-dimensional printing of cells, use of scaffolds and engineered heart tissue, with convincing human validation studies. Furthermore, our knowledge on the consequences of mutated proteins has deepened, with relevance for cellular homeostasis, protein quality control and toxicity, often specific to particular cardiomyopathies, with precise effects explaining the aberrations. This has opened up new avenues to treat cardiomyopathies, using contemporary techniques from the molecular toolbox, such as gene editing and repair using CRISPR-Cas9 techniques, antisense therapies, novel designer drugs, and RNA therapies. In this article, we discuss the connection between biology and diverse clinical presentation, as well as promising new medications and therapeutic avenues, which may be instrumental to come to precision medicine of genetic cardiomyopathies.

16.
Eur J Heart Fail ; 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34962044

RESUMO

AIMS: To perform a comprehensive characterization of acute heart failure (AHF) with preserved (HFpEF), versus mildly reduced (HFmrEF) versus reduced ejection fraction (HFrEF). METHODS AND RESULTS: Of 5951 participants in the ESC HF Long-Term Registry hospitalized for AHF (acute coronary syndromes excluded), 29% had HFpEF, 18% HFmrEF, and 53% HFrEF. Hospitalization reasons were most commonly atrial fibrillation (more in HFmrEF and HFpEF), followed by ischaemia (HFmrEF), infection (HFmrEF and HFpEF), worsening renal function (HFrEF), and uncontrolled hypertension (HFmrEF and HFpEF). Hospitalization characteristics included lower blood pressure, more oedema and higher natriuretic peptides with lower ejection fraction, similar pulmonary congestion, more mitral regurgitation in HFrEF and HFmrEF and more tricuspid regurgitation in HFrEF. In-hospital mortality was 3.4% in HFrEF, 2.1% in HFmrEF and 2.2% in HFpEF. Intravenous diuretic (∼80%) and nitrate (∼15%) use was similar but inotrope use greater in HFrEF (16%, vs. HFmrEF 7.4% vs. HFpEF 5.3%). Weight loss and estimated glomerular filtration rate improvement were greater in HFrEF, whereas reduction in natriuretic peptides was similar. Over 1 year post-discharge, events per 100 patient-years (95% confidence interval) in HFrEF versus HFmrEF versus HFpEF were: all-cause death 22 (20-24) versus 17 (14-20) versus 17 (15-20); cardiovascular (CV) death 12 (10-13) versus 8.6 (6.6-11) versus 8.4 (6.9-10); non-CV death 2.4 (1.8-3.1) versus 3.3 (2.1-4.8) versus 4.5 (3.5-5.9); all-cause hospitalization 48 (45-51) versus 35 (31-40) versus 42 (39-46); HF hospitalization 29 (27-32) versus 19 (16-22) versus 17 (15-20); and non-CV hospitalization 7.7 (6.6-8.9) versus 9.6 (7.5-12) versus 15 (13-17). CONCLUSION: In AHF, HFrEF is more severe and has greater in-hospital mortality. Post-discharge, HFrEF has greater CV risk, HFpEF greater non-CV risk, and HFmrEF lower overall risk.

17.
J Am Soc Nephrol ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732509

RESUMO

Background: Finerenone reduced risk of cardiorenal outcomes in patients with CKD and type 2 diabetes in the FIDELIO-DKD trial. We report incidences and risk factors for hyperkalemia with finerenone and placebo in FIDELIO-DKD. Methods: This post hoc safety analysis defined hyperkalemia as ≥mild or ≥moderate based on serum potassium concentrations of >5.5 or >6.0 mmol/L, respectively, assessed at all regular visits. Cumulative incidences of hyperkalemia were based on the Aalen-Johansen estimator using death as competing risk. A multivariate Cox proportional hazards model identified significant independent predictors of hyperkalemia. Restricted cubic splines assessed relationships between short-term post-baseline changes in serum potassium or eGFR and subsequent hyperkalemia risk. During the study, serum potassium levels guided drug dosing. Patients in either group who experienced ≥mild hyperkalemia had the study drug withheld until serum potassium was ≤5.0 mmol/L; then the drug was restarted at the 10 mg daily dose. Placebo-treated patients underwent sham treatment interruption and downtitration. Results: Over 2.6 years' median follow-up, 597/2785 (21.4%) and 256/2775 (9.2%) of patients treated with finerenone and placebo, respectively, experienced treatment-emergent ≥mild hyperkalemia; 126/2802 (4.5%) and 38/2796 (1.4%) patients, respectively, experienced moderate hyperkalemia. Independent risk factors for ≥mild hyperkalemia were higher serum potassium, lower eGFR, increased urine albumin-to-creatinine ratio, younger age, female sex, beta-blocker use, and finerenone assignment. Diuretic or sodium-glucose co-transporter-2 inhibitor use reduced risk. In both groups, short-term increases in serum potassium and decreases in eGFR were associated with subsequent hyperkalemia. At month 4, the magnitude of increased hyperkalemia risk for any change from baseline was smaller with finerenone than with placebo Conclusions: Finerenone was independently associated with hyperkalemia. However, routine potassium monitoring and hyperkalemia management strategies employed in FIDELIO-DKD minimized the impact of hyperkalemia, providing a basis for clinical use of finerenone.

19.
Eur J Heart Fail ; 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34800079

RESUMO

AIMS: In patients with current or a history of hyperkalaemia, treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) is often compromised. Patiromer, a novel potassium (K+ ) binder, may improve serum K+ levels and adherence to RAASi. METHODS: The DIAMOND trial will enroll ∼820 patients with heart failure with reduced ejection fraction (HFrEF; ejection fraction ≤40%). Patients meeting the screening criteria will enter a single-blinded run-in phase where they will be started or continued on a mineralocorticoid receptor antagonist (MRA) titrated to 50 mg/day and other RAASi therapy to ≥50% target dose, and patiromer. Patiromer will be titrated up to a maximum three packs/day (8.4 g/pack) to achieve optimal doses of RAASi without hyperkalaemia. The run-in phase will last up to 12 weeks, following which patients will undergo double-blind randomization in a 1:1 ratio to receive either continued patiromer or placebo (patiromer withdrawal). The primary endpoint is the mean difference in serum K+ from randomization between patiromer and placebo arms. Secondary endpoints will include hyperkalaemia events with K+ value >5.5 mEq/L, durable enablement of MRA at target dose, investigator-reported adverse events of hyperkalaemia, hyperkalaemia-related clinical endpoints and an overall RAASi use score (using a 0-8-point scale) comprising all-cause death, occurrence of cardiovascular hospitalization or usage of comprehensive heart failure medication. CONCLUSION: The DIAMOND trial is designed to determine if patiromer can favourably impact K+ control in patients with HFrEF with hyperkalaemia or a history of hyperkalaemia leading to RAASi therapy compromise, and in turn improve RAASi use.

20.
Circulation ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34775784

RESUMO

Background: Chronic kidney disease (CKD) and type 2 diabetes (T2D) are independently associated with heart failure (HF), a leading cause of morbidity and mortality. In the FIDELIO-DKD and FIGARO DKD trials, finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) improved cardiovascular outcomes in patients with albuminuric CKD and T2D. These prespecified analyses from FIGARO-DKD assessed the impact of finerenone on clinically important HF outcomes. Methods: Patients with T2D and albuminuric CKD (urine albumin-to-creatinine ratio [UACR] ≥30 to <300 mg/g and estimated glomerular filtration rate [eGFR] ≥25 to ≤90 ml/min/1.73 m2, or UACR ≥300 to ≤5000 mg/g and eGFR ≥60 ml/min/1.73 m2,), without symptomatic HF with reduced ejection fraction, were randomized to finerenone or placebo. Time-to-first event outcomes included: new-onset HF (first hospitalization for HF [HHF] in patients without a history of HF at baseline); cardiovascular death or first HHF; HF-related death or first HHF; first HHF; cardiovascular death or total (first or recurrent) HHF; HF-related death or total HHF; and total HHF. Outcomes were evaluated in the overall population and in prespecified subgroups categorized by baseline HF history (as reported by the investigators). Results: Overall, 7352 patients were included in these analyses; 571 (7.8%) had a history of HF at baseline. New-onset HF was significantly reduced with finerenone versus placebo (1.9% versus 2.8%; hazard ratio [HR], 0.68 [95% CI 0.50-0.93]; P=0.0162). In the overall population, the incidences of all HF outcomes analyzed were significantly lower with finerenone than placebo, including a 18% lower risk of cardiovascular death or first HHF (HR, 0.82 [95% CI 0.70-0.95]; P=0.011), a 29% lower risk of first HHF (HR, 0.71 [95% CI 0.56-0.90]; P=0.0043) and a 30% lower rate of total HHF (rate ratio, 0.70 [95% CI, 0.52- 0.94]). The effects of finerenone on improving HF outcomes were not modified by a history of HF. The incidence of treatment-emergent adverse events was balanced between treatment groups. Conclusions: The results from these FIGARO-DKD analyses demonstrate that finerenone reduces new-onset HF and improves other HF outcomes in patients with CKD and T2D, irrespective of a history of HF.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...