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1.
Artigo em Inglês | MEDLINE | ID: mdl-36639130

RESUMO

AIMS: Finerenone reduces the risk of cardiovascular events in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). We investigated the causes of mortality in the FIDELITY population. METHODS AND RESULTS: The FIDELITY prespecified pooled data analysis from FIDELIO-DKD and FIGARO-DKD excluded patients with heart failure and reduced ejection fraction. Outcomes included intention-to-treat and prespecified on-treatment analyses of the risk of all-cause and cardiovascular mortality. Of 13 026 patients (mean age, 64.8 years; mean estimated glomerular filtration rate [eGFR], 57.6 mL/min/1.73 m2), 99.8% were on renin-angiotensin system inhibitors. Finerenone reduced the incidence of all-cause and cardiovascular mortality vs. placebo (8.5% vs. 9.4% and 4.9% vs. 5.6%, respectively) and demonstrated significant on-treatment reductions (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.70-0.96; P = 0.014 and HR, 0.82; 95% CI, 0.67-0.99; P = 0.040, respectively). Cardiovascular-related mortality was most common, and finerenone lowered the incidence of sudden cardiac death vs. placebo (1.3% [incidence rate 0.44/100 patient-years] vs. 1.8% [0.58/100 patient-years], respectively; HR, 0.75; 95% CI, 0.57-0.996; P = 0.046). The effects of finerenone on mortality were similar across all Kidney Disease: Improving Global Outcomes risk groups. Event probability with finerenone at 4 years was consistent irrespective of baseline urine albumin-to-creatinine ratio, but seemingly more pronounced in patients with higher baseline eGFR. CONCLUSION: In FIDELITY, finerenone significantly reduced the risk of all-cause and cardiovascular mortality vs. placebo in patients with T2D across a broad spectrum of CKD stages while on treatment, as well as sudden cardiac death in the intention-to-treat population.

2.
J Am Heart Assoc ; 12(1): e027652, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36565199

RESUMO

Background Outcomes and treatment effects of therapy may vary according to the cause of heart failure (HF). Methods and Results In this post hoc analysis of the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial, the effect of empagliflozin on cardiovascular and renal outcomes was assessed according to the cause of HF. The cause of HF was investigator reported and stratified as ischemic or nonischemic. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs. Of the 3730 patients enrolled, 1929 (51.7%) had ischemic cause. In the placebo arm, patients with ischemic cause of HF did not have a significantly higher risk of cardiovascular mortality (HR, 1.21 [95% CI, 0.90-1.63]) and hospitalization for HF (HR, 0.90 [95% CI, 0.72-1.12]) compared with nonischemic cause. Empagliflozin compared with placebo significantly reduced the risk of cardiovascular death or hospitalization for HF in patients with ischemic and nonischemic cause (HR, 0.82 [95% CI, 0.68-0.99] for ischemic and HR, 0.67 [95% CI, 0.55-0.82] for nonischemic cause; P interaction=0.15). The benefit of empagliflozin on HF hospitalization, the renal composite end point, estimated glomerular filtration slope changes, and health status scores were also consistent in both groups without treatment by cause modification. Conclusions Empagliflozin offers cardiovascular and renal benefits in patients with heart failure with reduced ejection fraction regardless of the cause of HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Compostos Benzidrílicos/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/induzido quimicamente , Volume Sistólico , Disfunção Ventricular Esquerda/induzido quimicamente
3.
J Hypertens ; 41(2): 295-302, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36583355

RESUMO

OBJECTIVE: Finerenone is a selective nonsteroidal mineralocorticoid receptor antagonist with a short half-life. Its effects on cardiorenal outcomes were thought to be mediated primarily via nonhemodynamic pathways, but office blood pressure (BP) measurements were insufficient to fully assess hemodynamic effects. This analysis assessed the effects of finerenone on 24-h ambulatory BP in patients with chronic kidney disease and type 2 diabetes. METHODS: ARTS-DN (NCT01874431) was a phase 2b trial that randomized 823 patients with type 2 diabetes and chronic kidney disease, with urine albumin-to-creatinine ratio ≥30 mg/g and estimated glomerular filtration rate of 30-90 ml/min per 1.73 m2 to placebo or finerenone (1.25-20 mg once daily in the morning) administered over 90 days. Ambulatory BP monitoring (ABPM) over 24 h was performed in a subset of 240 patients at screening, Day 60, and Day 90. RESULTS: Placebo-adjusted change in 24-h ABPM systolic BP (SBP) at Day 90 was -8.3 mmHg (95% confidence interval [CI], -16.6 to 0.1) for finerenone 10 mg (n = 27), -11.2 mmHg (95% CI, -18.8 to -3.6) for finerenone 15 mg (n = 34), and -9.9 mmHg (95% CI, -17.7 to -2.0) for finerenone 20 mg (n = 31). Mean daytime and night-time SBP recordings were similarly reduced and finerenone did not increase the incidence of SBP dipping. Finerenone produced a persistent reduction in SBP over the entire 24-h interval. CONCLUSIONS: Finerenone reduced 24-h, daytime, and night-time SBP. Despite a short half-life, changes in BP were persistent over 24 h with once-daily dosing in the morning.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico
4.
Nat Med ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36471037

RESUMO

The EMPEROR-Preserved trial showed that the sodium-glucose co-transporter 2 inhibitor empagliflozin significantly reduces the risk of cardiovascular death or hospitalization for heart failure (HHF) in heart failure patients with left ventricular ejection fraction (LVEF) > 40%. Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (≥ 50%) (n = 4,005; 66.9%) or mid-range (41-49%). In patients with LVEF ≥ 50%, empagliflozin reduced the risk of cardiovascular death or HHF (the primary endpoint) by 17% versus placebo (hazard ratio (HR) 0.83; 95% confidence interval (CI): 0.71-0.98, P = 0.024). For the key secondary endpoint, the HR for total HHF was 0.83 (95%CI: 0.66-1.04, P = 0.11). For patients with an LVEF of 41-49%, the HR for empagliflozin versus placebo was 0.71 (95%CI: 0.57-0.88, P = 0.002) for the primary outcome (Pinteraction = 0.27), and 0.57 (95%CI: 0.42-0.79, P < 0.001) for total HHF (Pinteraction = 0.06). These results, together with those from the EMPEROR-Reduced trial in patients with LVEF < 40%, support the use of empagliflozin across the full spectrum of LVEF in heart failure.

5.
JACC Heart Fail ; 10(12): 889-901, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36456063

RESUMO

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and the Academic Research Consortium (ARC) composed of patients, academic investigators from the United States and Europe, the U.S. Food and Drug Administration, the National Institutes of Health, payers, and industry. Members discussed the measure, remote capture, and clinical utility of functional and quality-of-life endpoints for use in clinical trials of heart failure and cardiovascular therapeutics, with the goal of improving the efficiency of heart failure and cardiovascular clinical research, evidence generation, and thereby patient quality of life, functional status, and survival. Assessments of patient-reported outcomes and maximal and submaximal exercise tolerance are standardized and validated, but actigraphy remains inconsistent as a potential endpoint. This paper details those discussions and consensus recommendations.


Assuntos
Insuficiência Cardíaca , Estados Unidos , Humanos , Insuficiência Cardíaca/terapia , Qualidade de Vida , Tolerância ao Exercício , Pesquisadores , National Institutes of Health (U.S.)
6.
Artigo em Inglês | MEDLINE | ID: mdl-36510826

RESUMO

AIMS: Psychoeducational interventions focusing on self-management of heart failure (HF) patients may improve patient health knowledge and reduce hospitalizations, but data regarding the effects on caregiver outcomes are inconclusive. METHODS AND RESULTS: We conducted a single-center, randomized controlled study to evaluate the effect of a nurse-led educational intervention in dyads of recently hospitalized HF patients and their caregivers on caregiver burden, feelings of guilt and health-related quality of life (HR-QoL). Dyads were randomized to usual care plus intervention group 1 (IG-1) or 2 (IG-2) or usual care only (control group, CG). Educational sessions in IG-1 and IG-2 were initiated before hospital discharge and continued with combination of home visits and telephone sessions in IG-1, or telephone sessions only in IG-2, delivered on regular intervals for 6 months. Caregiver burden was assessed by Heart Failure Caregiver Questionnaire (HF-CQ v5.0), guilt by Caregiver Guilt Questionnaire (CGQ) and QOL by EuroQol EQ-5D. Fifty-seven patient/caregiver dyads were included: 12 in IG-1, 18 in IG-2 and 27 in CG, of whom 11, 16, and 20, respectively, completed the study. All domains of HF-CQ and CGQ improved in IG-1 and IG-2 at 6 months, whereas deteriorated in CG (all p < 0.01). EQ-5D improved in IG-1 and IG-2 only in visual analogue scale part (p = 0.002), but not in the descriptive part. CONCLUSIONS: A nurse-led, 6-month educational intervention on recently hospitalized HF patients/caregiver dyads, delivered through either combined home visits and telephone sessions or telephone sessions only, reduced caregiver burden and feelings of guilt, with lesser effect on HR-QoL.

7.
Eur Heart J ; 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36478225

RESUMO

AIMS: Empagliflozin reduces the risk of cardiovascular death or heart failure (HF) hospitalization in patients with HF and preserved ejection fraction. This study aims to evaluate if systolic blood pressure (SBP) moderates these effects. METHODS AND RESULTS: The association of SBP and the treatment effects of empagliflozin in EMPEROR-Preserved (empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction) was evaluated. Randomized patients (n = 5988) were grouped according to SBP at baseline (<110 mmHg, n = 455; 110-130 mmHg, n = 2415; > 130 mmHg, n = 3118). The effect of empagliflozin on blood pressure, cardiovascular death or HF hospitalization (primary outcome), total HF hospitalizations, and rate of decline in estimated glomerular filtration rate was studied. Over a median of 26.2 months, the placebo-corrected decline was small and not significantly different across baseline SBP. On placebo, the risk of cardiovascular death or hospitalization for HF was 8.58 at >130 mmHg, 8.26 at 110-130 mmHg, and 11.59 events per 100 patient-years at <110 mmHg (P = 0.12 vs. > 130 mmHg, P = 0.08 vs. 110-130 mmHg). There was no evidence for baseline SBP moderating the effect of empagliflozin on risk of HF events (primary endpoint interaction P = 0.69, recurrent HF hospitalizations interaction P = 0.55). When comparing empagliflozin with placebo, SBP did not meaningfully associate with adverse events such as hypotension, volume depletion, and acute renal failure. CONCLUSION: In EMPEROR-Preserved, empagliflozin was effective and safe without SBP meaningfully moderating empagliflozin's treatment effects. This analysis of EMPEROR-Preserved shows that empagliflozin can be used safely and effectively without blood pressure being a meaningful moderator of the drug benefit. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov Unique identifier: NCT03057951.

8.
Lancet ; 400(10367): 1938-1952, 2022 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-36356631

RESUMO

BACKGROUND: There is a paucity of evidence for dose and pace of up-titration of guideline-directed medical therapies after admission to hospital for acute heart failure. METHODS: In this multinational, open-label, randomised, parallel-group trial (STRONG-HF), patients aged 18-85 years admitted to hospital with acute heart failure, not treated with full doses of guideline-directed drug treatment, were recruited from 87 hospitals in 14 countries. Before discharge, eligible patients were randomly assigned (1:1), stratified by left ventricular ejection fraction (≤40% vs >40%) and country, with blocks of size 30 within strata and randomly ordered sub-blocks of 2, 4, and 6, to either usual care or high-intensity care. Usual care followed usual local practice, and high-intensity care involved the up-titration of treatments to 100% of recommended doses within 2 weeks of discharge and four scheduled outpatient visits over the 2 months after discharge that closely monitored clinical status, laboratory values, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations. The primary endpoint was 180-day readmission to hospital due to heart failure or all-cause death. Efficacy and safety were assessed in the intention-to-treat (ITT) population (ie, all patients validly randomly assigned to treatment). The primary endpoint was assessed in all patients enrolled at hospitals that followed up patients to day 180. Because of a protocol amendment to the primary endpoint, the results of patients enrolled on or before this amendment were down-weighted. This study is registered with ClinicalTrials.gov, NCT03412201, and is now complete. FINDINGS: Between May 10, 2018, and Sept 23, 2022, 1641 patients were screened and 1078 were successfully randomly assigned to high-intensity care (n=542) or usual care (n=536; ITT population). Mean age was 63·0 years (SD 13·6), 416 (39%) of 1078 patients were female, 662 (61%) were male, 832 (77%) were White or Caucasian, 230 (21%) were Black, 12 (1%) were other races, one (<1%) was Native American, and one (<1%) was Pacific Islander (two [<1%] had missing data on race). The study was stopped early per the data and safety monitoring board's recommendation because of greater than expected between-group differences. As of data cutoff (Oct 13, 2022), by day 90, a higher proportion of patients in the high-intensity care group had been up-titrated to full doses of prescribed drugs (renin-angiotensin blockers 278 [55%] of 505 vs 11 [2%] of 497; ß blockers 249 [49%] vs 20 [4%]; and mineralocorticoid receptor antagonists 423 [84%] vs 231 [46%]). By day 90, blood pressure, pulse, New York Heart Association class, bodyweight, and NT-proBNP concentration had decreased more in the high-intensity care group than in the usual care group. Heart failure readmission or all-cause death up to day 180 occurred in 74 (15·2% down-weighted adjusted Kaplan-Meier estimate) of 506 patients in the high-intensity care group and 109 (23·3%) of 502 patients in the usual care group (adjusted risk difference 8·1% [95% CI 2·9-13·2]; p=0·0021; risk ratio 0·66 [95% CI 0·50-0·86]). More adverse events by 90 days occurred in the high-intensity care group (223 [41%] of 542) than in the usual care group (158 [29%] of 536) but similar incidences of serious adverse events (88 [16%] vs 92 [17%]) and fatal adverse events (25 [5%] vs 32 [6%]) were reported in each group. INTERPRETATION: An intensive treatment strategy of rapid up-titration of guideline-directed medication and close follow-up after an acute heart failure admission was readily accepted by patients because it reduced symptoms, improved quality of life, and reduced the risk of 180-day all-cause death or heart failure readmission compared with usual care. FUNDING: Roche Diagnostics.


Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular Esquerda , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Resultado do Tratamento
9.
JACC Heart Fail ; 10(11): 860-870, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36328655

RESUMO

BACKGROUND: In patients with type 2 diabetes (T2D), risks of cardiovascular mortality and heart failure (HF) increase with decreasing kidney function (estimated glomerular filtration rate [eGFR]) and increasing albuminuria (urine albumin-to-creatinine ratio [UACR]). Finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and T2D in FIDELITY (Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis). OBJECTIVES: This study sought to evaluate the effects of finerenone on HF outcomes by eGFR and/or UACR categories. METHODS: FIDELITY included 13,026 patients with T2D and CKD (UACR 30-5,000 mg/g and eGFR ≥25 mL/min/1.73 m2) randomized to finerenone or placebo. Time-to-event outcomes were first hospitalization for heart failure (HHF), cardiovascular death or first HHF, recurrent HHF, and cardiovascular death or recurrent HHF, analyzed in subgroups by baseline eGFR (<60 and ≥60 mL/min/1.73 m2) and/or UACR (<300 and ≥300 mg/g). RESULTS: Compared with placebo, finerenone significantly reduced risk of first HHF (HR: 0.78 [95% CI: 0.66-0.92]; P = 0.003), cardiovascular death or first HHF (HR: 0.83 [95% CI: 0.74-0.93]; P = 0.002), recurrent HHF (HR: 0.79 [95% CI: 0.64-0.96]; P = 0.021), and cardiovascular death or recurrent HHF (HR: 0.82 [95% CI: 0.72-0.95]; P = 0.006). The risk of outcomes increased across baseline eGFR and UACR categories; lowest incidences were seen in patients with an eGFR ≥60 mL/min/1.73 m2 and a UACR <300 mg/g. Finerenone improved HF outcomes irrespective of baseline eGFR and/or UACR categories (all P interaction values >0.10). CONCLUSIONS: Compared with placebo, finerenone improved HF-related outcomes in patients with CKD and T2D, with consistent benefits across eGFR and/or UACR categories. (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD], NCT02540993; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Chronic Kidney Disease [FIGARO-DKD], NCT02545049).


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Insuficiência Renal Crônica , Humanos , Albuminúria/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Resultado do Tratamento
11.
J Card Fail ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332897

RESUMO

BACKGROUND: The six-minute walk test (6MWT) is widely used to measure exercise capacity; however, the magnitude of change that is clinically meaningful for individuals is not well established in heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: To calculate the minimal clinically important difference (MCID) for change in exercise capacity on the 6MWT in iron-deficient HFrEF populations. METHODS: In this pooled secondary analysis of FAIR-HF and CONFIRM-HF trials, mean changes in 6MWT from baseline to weeks 12 and 24 were calculated and calibrated against the Patient Global Assessment (PGA) tool [clinical anchor] to derive MCIDs for improvement and deterioration. RESULTS: Of 760 patients included in the two trials, 6MWT and PGA data were available for 680 (89%) and 656 (86%) patients at weeks 12 and 24, respectively. The mean 6MWT distance at baseline was 281±103m. There was a modest correlation between changes in 6MWT and PGA from baseline to week 12 (r=0.31, p<0.0001) and week 24 (r=0.43, p<0.0001). Respective estimates (95% confidence intervals) for MCID in 6MWT at weeks 12 and 24 were 14m (5;23) and 15m (3;27) for a "little improvement" (vs no change), 20m (10;30) and 24m (12;36) for "moderate improvement" vs a "little improvement", -11m (-32;9.2) and -31m (-53;-8) for a "little deterioration" (vs no change), and -84m (-144;-24) and -69m (-118;-20) for "moderate deterioration" vs a "little deterioration". CONCLUSIONS: The MCID for improvement in exercise capacity on the 6MWT was 14-15m in patients with HFrEF and iron deficiency. These MCIDs can aid clinical interpretation of study data.

12.
J Card Fail ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332898

RESUMO

BACKGROUND: Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF). METHODS AND RESULTS: We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death. CONCLUSIONS: In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes.

14.
Kidney Int ; 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36367466

RESUMO

In FIDELITY, a prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD studies, finerenone was found to improve cardiorenal outcomes in patients with type 2 diabetes, a urine albumin-to-creatinine ratio of 30-5000 mg/g, an estimated glomerular filtration rate (eGFR) of 25 ml/min per 1.73 m2 or more and also receiving optimized renin-angiotensin system blockade treatment. This present analysis focused on the efficacy and safety of finerenone on kidney outcomes. Among 13,026 patients with a median follow-up of three years, finerenone significantly reduced the hazard of a kidney composite outcome (time to kidney failure, sustained 57% or more decrease in eGFR from baseline, or kidney death) by 23% versus placebo (hazard ratio, 0.77; 95% confidence interval, 0.67-0.88), with a three-year absolute between-group difference of 1.7% (95% confidence interval, 0.7-2.6). Hazard ratios were directionally consistent for a prespecified baseline eGFR and urine albumin-to-creatinine ratio categories (Pinteraction = 0.62 and Pinteraction = 0.67, respectively), although there was a high degree of uncertainty in the 30-300 mg/g subgroup. Finerenone significantly reduced the hazard of end-stage kidney disease (ESKD) by 20% versus placebo (0.80; 0.64-0.99). Adverse events were similar between treatment arms, although hyperkalemia leading to treatment discontinuation occurred significantly more frequently with finerenone versus placebo (2.4% vs 0.8% and 0.6% vs 0.3% in patients with eGFR less than 60 vs. greater than or equal to 60 ml/min per 1.73 m2, respectively). Thus, finerenone improved kidney outcomes, reduced the hazard of ESKD, and is well tolerated in patients with chronic kidney disease and type 2 diabetes.

15.
Circulation ; 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36335479

RESUMO

BACKGROUND: Acetazolamide inhibits proximal tubular sodium reabsorption and improved decongestion in the Acetazolamide in Decompensated heart failure with Volume OveRload (ADVOR) trial. It remains unclear whether the decongestive effects of acetazolamide differ across the spectrum of left ventricular ejection fraction (LVEF). METHODS: This is a pre-specified analysis of the randomized, double blind, placebo-controlled ADVOR trial that enrolled 519 patients with acute heart failure, clinical signs of volume overload (edema, pleural effusion or ascites), NTproBNP >1,000 ng/L or BNP >250 ng/ml, to receive intravenous acetazolamide (500 mg once daily) or placebo on top of standardized intravenous loop diuretics (twice oral home maintenance dose). Randomization was stratified according to LVEF (≤40% or >40%). The primary endpoint was successful decongestion, defined as the absence of signs of volume overload within three days from randomization without the need for mandatory escalation of decongestive therapy because of poor urine output. RESULTS: Median LVEF was 45% (25-75th percentile: 30-55%) and 43% had a LVEF ≤40%. Patients with lower LVEF were younger, more likely to be male, with a higher prevalence of ischemic heart disease, a higher NTproBNP, less atrial fibrillation, and lower estimated glomerular filtration rate. No interaction on the overall beneficial treatment effect of acetazolamide on the primary endpoint of Successful decongestion (OR=1.77, 95% CI=[1.18-2.63], p=0.005, all p-values for interaction >0.401) was found when LVEF was assessed per randomization stratum (≤/ >40%), or as HFrEF, HFmrEF and HFpEF, or on a continuous scale. Acetazolamide resulted in improved diuretic response measured by higher cumulative diuresis and natriuresis and shortened length of stay without treatment effect modification by baseline LVEF (all p-values for interaction >0.160). CONCLUSIONS: Acetazolamide when added to treatment with loop diuretics in patients with AHF improves the incidence of successful decongestion, improves diuretic response and shortens length of stay, without treatment effect modification by baseline LVEF.

16.
Eur J Heart Fail ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36325584

RESUMO

AIMS: Baseline body mass index (BMI) and weight loss promoted by sodium-glucose cotransporter 2 inhibitors may impact outcomes in patients with heart failure with reduced ejection fraction (HFrEF). We assessed in the EMPEROR-Reduced population treated with empagliflozin versus placebo the relationship between baseline BMI, weight loss and effects on the primary (time to first hospitalization for heart failure [HHF] or cardiovascular death) and key secondary outcomes. METHODS AND RESULTS: We categorized patients according to their baseline BMI: <20 kg/m2 (n = 180); 20 to <25 kg/m2 (n = 1038); 25 to <30 kg/m2 (n = 1345); 30 to <35 kg/m2 (n = 774) and ≥35 kg/m2 (n = 393). The treatment effect of empagliflozin on the primary outcome was consistent across all BMI categories (hazard ratios in subgroups 0.66-0.88, interaction trend p = 0.32), as was the effect on total (first plus recurrent) HHF (interaction trend p = 0.31). Empagliflozin reduced the rate of estimated glomerular filtration rate decline consistently across the BMI categories (interaction trend p = 0.67). Overall, incidence rates of any or serious adverse events were comparable between the treatment groups across all BMI categories. A total of 313 (17.4%) patients treated with empagliflozin experienced a weight loss of more than 5% at week 52 versus 230 (12.8%) in placebo. When analysed separately within each treatment group, presence of weight loss was similarly associated with an increased risk of all-cause mortality. CONCLUSION: The benefits of empagliflozin versus placebo were consistently present across all BMI categories in HFrEF patients. Weight loss was associated with higher risk of all-cause mortality, regardless of treatment group.

17.
ESC Heart Fail ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36325747

RESUMO

AIMS: Kidney function changes dynamically during AHF treatment, but risk factors for and consequences of worsening renal function (WRF) at hospital admission are uncertain. We aimed to determine the significance of WRF at admission for acute heart failure (AHF). METHODS AND RESULTS: We evaluated a subgroup of 406 patients from The Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic heart failure Study (AKINESIS) who had serum creatinine measurements available within 3 months before and at the time of admission. Admission WRF was primarily defined as a 0.3 mg/dL or 50% creatinine increase from preadmission. Alternative definitions evaluated were a ≥0.5 mg/dL creatinine increase, ≥25% glomerular filtration rate decrease, and an overall change in creatinine. Predictors of admission WRF were evaluated. Outcomes evaluated were length of hospitalization, a composite of adverse in-hospital events, and the composite of death or HF readmission at 30, 90, and 365 days. Biomarkers' prognostic ability for these outcomes were evaluated in patients with admission WRF. One-hundred six patients (26%) had admission WRF. These patients had features of more severe AHF with lower blood pressure, higher BUN, and lower serum sodium concentrations at admission. Higher BNP (odds ratio [OR] per doubling 1.16-1.28, 95% confidence interval [CI] 1.00-1.55) and lower diastolic blood pressure (OR 0.97-0.98, 95% CI 0.96-0.99) were associated with a higher odds for the three definitions of admission WRF. The primary WRF definition was not associated with a longer hospitalization, but alternative WRF definitions were (1.3 to 1.6 days longer, 95% CI 1.0-2.2). WRF across definitions was not associated with a higher odds of adverse in-hospital events or a higher risk of death or HF readmission. In the subset of patients with WRF, biomarkers were not prognostic for any outcome. CONCLUSIONS: Admission WRF is common in AHF patients and is associated with an increased length of hospitalization, but not adverse in-hospital events, death, or HF readmission. Among those with admission WRF, biomarkers did not risk stratify for adverse events.

18.
Eur J Heart Fail ; 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36196060

RESUMO

AIM: Acute heart failure can be a life-threatening medical condition. Delaying administration of intravenous furosemide (time-to-diuretics) has been postulated to increase mortality, but prior reports have been inconclusive. We aimed to evaluate the association between time-to-diuretics and mortality in the international REPORT-HF registry. METHODS AND RESULTS: We assessed the association of time-to-diuretics within the first 24 h with in-hospital and 30-day post-discharge mortality in 15 078 patients from seven world regions in the REPORT-HF registry. We further tested for effect modification by baseline mortality risk (ADHERE risk score), left ventricular ejection fraction (LVEF) and region. The median time-to-diuretics was 67 (25th-75th percentiles 17-190) min. Women, patients with more signs and symptoms of heart failure, and patients from Eastern Europe or Southeast Asia had shorter time-to-diuretics. There was no significant association between time-to-diuretics and in-hospital mortality (p > 0.1). The 30-day mortality risk increased linearly with longer time-to-diuretics (administered between hospital arrival and 8 h post-hospital arrival) (p = 0.016). This increase was more significant in patients with a higher ADHERE risk score (pinteraction  = 0.008), and not modified by LVEF or geographic region (pinteraction > 0.1 for both). CONCLUSION: In REPORT-HF, longer time-to-diuretics was not associated with higher in-hospital mortality. However, we did found an association with increased 30-day mortality, particularly in high-risk patients, and irrespective of LVEF or geographic region. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02595814.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36251465

RESUMO

AIMS: Finerenone, a selective, non-steroidal mineralocorticoid receptor antagonist, improves cardiovascular (CV) and kidney outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). This subgroup analysis of FIDELITY, a pre-specified, pooled, individual patient-data analysis of FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049), compared finerenone vs. placebo in patients with and without baseline history of atherosclerotic CV disease (ASCVD). METHODS AND RESULTS: Outcomes included a composite CV outcome (CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure [HHF]); CV death or HHF; a composite kidney outcome (kidney failure, sustained estimated glomerular filtration rate decrease ≥ 57%, or kidney-related death); all-cause mortality; and safety by baseline history of ASCVD.Of 13 026 patients, 5935 (45.6%) had a history of ASCVD. The incidence of the composite CV outcome, CV death or HHF, and all-cause mortality was higher in patients with ASCVD vs. those without, with no difference between groups in the composite kidney outcome. Finerenone consistently reduced outcomes vs. placebo in patients with and without ASCVD (P-interaction for the composite CV outcome, CV death or HHF, the composite kidney outcome, and all-cause mortality 0.38, 0.68, 0.33, and 0.38, respectively). Investigator-reported treatment-emergent adverse events were consistent between treatment arms across ASCVD subgroups. CONCLUSION: Finerenone reduced the risk of CV and kidney outcomes consistently across the spectrum of CKD in patients with T2D, irrespective of prevalent ASCVD.

20.
Hypertension ; 79(12): 2685-2695, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36252131

RESUMO

BACKGROUND: Chronic kidney disease is frequently associated with hypertension and poorly controlled blood pressure can lead to chronic kidney disease progression. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, significantly improves cardiorenal outcomes in patients with chronic kidney disease and type 2 diabetes. This analysis explored the relationship between office systolic blood pressure (SBP) and cardiorenal outcomes with finerenone in FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease). METHODS: Patients with type 2 diabetes, urine albumin-to-creatinine ratio 30 to 5000 mg/g, and estimated glomerular filtration rate of 25 to <75 mL/min per 1.73 m2 receiving optimized renin-angiotensin system blockade, were randomized to finerenone or placebo. For this analysis, patients (N=5669) were grouped by baseline office SBP quartiles. RESULTS: Finerenone reduced office SBP across the baseline office SBP quartiles, including patients with baseline office SBP of >148 mm Hg. Overall, patients with lower baseline office SBP quartile and greater declines from baseline in SBP were associated with better cardiorenal outcomes. The risk of primary kidney and key secondary cardiovascular composite outcomes was consistently reduced with finerenone versus placebo irrespective of baseline office SBP quartiles (P for interaction 0.87 and 0.78, respectively). A time-varying analysis revealed that 13.8% and 12.6% of the treatment effect with finerenone was attributed to the change in office SBP for the primary kidney composite outcome and the key secondary cardiovascular outcome, respectively. CONCLUSIONS: In FIDELIO-DKD, cardiorenal outcomes improved with finerenone irrespective of baseline office SBP. Reductions in office SBP accounted for a small proportion of the treatment effect on cardiorenal outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02540993.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Albuminúria/tratamento farmacológico , Pressão Sanguínea , Método Duplo-Cego , Naftiridinas/uso terapêutico , Naftiridinas/farmacologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/farmacologia
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