scholarly journals 633 Efficacy of additional medical therapies in patients with heart failure, reduced ejection fraction, and chronic kidney disease already receiving neurohormonal inhibitors: a network meta-analysis

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Vincenzo De Marzo ◽  
Lucia Tricarico ◽  
Giuseppe Biondi Zoccai ◽  
Michele Correale ◽  
Natale Daniele Brunetti ◽  
...  

Abstract Aims We assessed the efficacy of add-on drugs in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant chronic kidney disease (CKD) already receiving neurohormonal inhibition (NEUi). Methods and results The literature was systematically searched for phase 3 randomized controlled trials (RCTs) involving ≥90% patients with left ventricular ejection fraction <45%, of whom <30% were acutely decompensated, and with published information about the subgroup of estimated glomerular filtration rate <60 ml/min/1.73 m2. Six RCTs were included in a study-level network meta-analysis evaluating the effect of NEUi, ivabradine, angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil (OM) on a composite outcome of cardiovascular death or hospitalization for heart failure. In a fixed-effects model, SGLT2i (HR: 0.78, 95% CrI: 0.69–0.89), ARNI (HR: 0.79, 95% CrI: 0.69–0.90), and ivabradine (HR: 0.82, 95% CrI: 0.69–0.98) decreased the risk of the composite outcome vs. NEUi, whereas OM did not (HR: 0.98, 95% CrI: 0.89–1.10). A trend for improved outcome was also found for vericiguat (HR: 0.90, 95% CrI: 0.80–1.00). In indirect comparisons, both SLGT2i (HR: 0.80, 95% CrI: 0.68–0.94) and ARNI (HR: 0.80, 95% CrI: 0.68–0.95) reduced the risk vs. OM; furthermore, there was a trend for a greater benefit of SGLT2i vs. vericiguat (HR: 0.88, 95% CrI: 0.73–1.00) and ivabradine vs. OM (HR: 0.84, 95% CrI: 0.68–1.00). Results were comparable in a random-effects model and in sensitivity analyses. SUCRA scores were 81.8%, 80.8%, 68.9%, 44.2%, 16.6%, and 7.8% for SGLT2i, ARNI, ivabradine, vericiguat, OM, and NEUi, respectively. Conclusions Expanding pharmacotherapy beyond NEUi improves outcomes in HFrEF with CKD. 633 Figure

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Edouard L Fu ◽  
Alicia Uijl ◽  
Friedo W Dekker ◽  
Lars H Lund ◽  
Gianluigi Savarese ◽  
...  

Abstract Background and Aims Beta-blockers reduce mortality and morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, patients with advanced chronic kidney disease (CKD) were underrepresented in landmark trials. We evaluated if beta-blockers are associated with improved survival in patients with HFrEF and advanced CKD. Method We identified 3906 persons with an ejection fraction <40% and advanced CKD (eGFR <30 mL/min/1.73m2) enrolled in the Swedish Heart Failure Registry during 2001-2016. The associations between beta-blocker use, 5-year all-cause mortality, and the composite of time to cardiovascular (CV) mortality/first HF hospitalization were assessed by multivariable Cox regression. Analyses were adjusted for 36 variables, including demographics, laboratory measures, comorbidities, medication use, medical procedures, and socioeconomic status. To assess consistency, the same analyses were performed in a positive control cohort of 12,673 patients with moderate CKD (eGFR <60-30 mL/min/1.73m2). Results The majority (89%) of individuals with HFrEF and advanced CKD received treatment with beta-blockers. Median (IQR) age was 81 (74-86) years, 36% were women and median eGFR was 26 (20-28) mL/min/173m2. During 5 years of follow-up, 2086 (53.4%) individuals had a subsequent HF hospitalization, and 2954 (75.6%) individuals died, of which 2089 (70.1%) due to cardiovascular causes. Beta-blocker use was associated with a significant reduction in 5-year all-cause mortality [adjusted hazard ratio (HR) 0.86; 95% confidence interval (CI) 0.76-0.96)] and CV mortality/HF hospitalization (HR 0.87; 95% CI 0.77-0.98). The magnitude of the associations between beta-blocker use and outcomes was similar to that observed for HFrEF patients with mild/moderate CKD, with adjusted HRs for all-cause mortality and CV mortality/HF hospitalization of 0.85 (95% CI 0.78-0.91) and 0.88 (95% CI 0.82-0.96), respectively. Conclusion Despite lack of trial evidence, the use of beta-blockers in patients with HFrEF and advanced CKD was high in routine Swedish care, and was independently associated with reduced mortality to the same degree as HFrEF with moderate CKD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyue Mee Kim ◽  
In-Chang Hwang ◽  
Wonsuk Choi ◽  
Yeonyee E. Yoon ◽  
Goo-Yeong Cho

AbstractAngiotensin receptor-neprilysin inhibitor (ARNI) and sodium–glucose co-transporter-2 inhibitor (SGLT2i) have shown benefits in diabetic patients with heart failure with reduced ejection fraction (HFrEF). However, their combined effect has not been revealed. We retrospectively identified diabetic patients with HFrEF who were prescribed an ARNI and/or SGLT2i. The patients were divided into groups treated with both ARNI and SGLT2i (group 1), ARNI but not SGLT2i (group 2), SGLT2i but not ARNI (group 3), and neither ARNI nor SGLT2i (group 4). After propensity score-matching, the occurrence of hospitalization for heart failure (HHF), cardiovascular mortality, and changes in echocardiographic parameters were analyzed. Of the 206 matched patients, 92 (44.7%) had to undergo HHF and 43 (20.9%) died of cardiovascular causes during a median 27.6 months of follow-up. Patients in group 1 exhibited a lower risk of HHF and cardiovascular mortality compared to those in the other groups. Improvements in the left ventricular ejection fraction and E/e′ were more pronounced in group 1 than in groups 2, 3 and 4. These echocardiographic improvements were more prominent after the initiation of ARNI, compare to the initiation of SGLT2i. In diabetic patients with HFrEF, combination of ARNI and SGT2i showed significant improvement in cardiac function and prognosis. ARNI-SGLT2i combination therapy may improve the clinical course of HFrEF in diabetic patients.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
O Obertynska

Abstract Purpose Mineralocorticoid receptor antagonists (MRAs) remain underused in cases of heart failure with a reduced left ventricular ejection fraction (HFrEF) and chronic kidney disease (CKD), largely due to the fear of inducing worsening of renal function (RF) and hyperkalemia (HK), particularly in combination with renin angiotensin inhibitors. The aim was to investigate the safety use of spironolactone (SP) in patients with HFrEF (ejection fraction <40%) and CKD and determine predictors of worsening of RF and developing HK. Methods 208 patients with HFrEF (on top of standard therapy including ACE-I or an ARB) and CKD (baseline eGFR between 30 and 60 ml/min) were included in the study. The potassium (K) and creatinine (C) levels, plasma aldosterone (AS) and NT-proBNP were estimated at baseline and at week 12. After biochemical evaluation, 101 patients started on SP treatment with a median dose of 23 mg daily (titrated). K and RF were checked at weeks 1, 2, 4, 6, 8, 12. Results K and C levels increased significantly after start of SP: mean K levels increased from 4.47±0.59 to 5.23±0.57 mEq/l, (P<0.01) and was dose dependent. After 12 weeks of treatment the incidence of severe HK (K+ ≥6.0 mmol/L) was <5%, K 5.5–5.9 mmol/L occurred in 13 patients (13%) and it was predicted by baseline eGFR≤35 ml/min/1.73 m2. and K ≥5.0 mmol/L/. Subsequently, these patients required a prescription of K binders. Mean eGFR on SP decreased from 48.34±2.23 to 42.19±2.65 ml/min/1.73 m2 (P<0.01) and a significant decrease in GFR was observed only during the first month (P <0.01) with not significant increasing to 6 and 12 weeks after the start of SP. Five patients (5%) on SP experienced significant decline of RF result in withdrew SP. Age, NT-proBNP concentration >1550 ng/L and eGFR ≤35 ml/min/1.73 m2 at baseline had modest discriminative powers for predicting decline of RF (0.456, P<0.01; 0.542, P<0.001; 0.712, P<0.001; respectively). At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.298, p<0.001). The SP treatment resulted in significantly reduced NT-proBNP and AS (P<0.01; P<0.05 respectively). By linear regression analysis in SP group the eGFR was associated with NT-proBNP change (0.362, P<0.05). Conclusion In patient with HFrEF and CKD the risk-benefit ratio of spironolactone with respect to renal failure appears favourable due to improvement of the neurohumoral profile. Although the renal disfunction and hyperkalemia on spironolactone are common: approximately 18% patients required the prescription of K binders and 5% required the withdrew SP duo to decline RF, the occurrence of hyperkalemia was predicted by baseline potassium level and eGFR. Age, higher level of NT-proBNP and eGFR were identified as potential predictors of worsening of RF. So, caution should be advised when using spironolactone in HFrEF with CKD and potassium of ≥5.0 mmol/L and eGFR ≤35 ml/min/1.73 m2 and NT-proBNP concentration >1550 ng/L for safety reasons. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Medical University


2020 ◽  
Vol 13 (7) ◽  
Author(s):  
Adam D. DeVore ◽  
Anne S. Hellkamp ◽  
Laine Thomas ◽  
Nancy M. Albert ◽  
Javed Butler ◽  
...  

Background: Among patients with heart failure (HF) with reduced ejection fraction (EF), improvements in left ventricular EF (LVEF) are associated with better outcomes and remain an important treatment goal. Patient factors associated with LVEF improvement in routine clinical practice have not been clearly defined. Methods: CHAMP-HF (Change the Management of Patients with Heart Failure) is a prospective registry of outpatients with HF with reduced EF. Assessments of LVEF are recorded when performed for routine care. We analyzed patients with both baseline and ≥1 follow-up LVEF assessments to describe factors associated with LVEF improvement. Results: In CHAMP-HF, 2623 patients had a baseline and follow-up LVEF assessment. The median age was 67 (interquartile range, 58–75) years, 40% had an ischemic cardiomyopathy, and median HF duration was 2.8 years (0.7–6.8). Median LVEF was 30% (23–35), and median change on follow-up was 4% (−2 to −13); 19% of patients had a decrease in LVEF, 31% had no change, 49% had a ≥5% increase, and 34% had a ≥10% increase. In a multivariable model, the following factors were associated with ≥5% LVEF increase: shorter HF duration (odds ratio [OR], 1.21 [95% CI, 1.17–1.25]), no implantable cardioverter defibrillator (OR, 1.46 [95% CI, 1.34–1.55]), lower LVEF (OR, 1.15 [95% CI, 1.10–1.19]), nonischemic cardiomyopathy (OR, 1.24 [95% CI, 1.09–1.36]), and no coronary disease (OR, 1.20 [95% CI, 1.03–1.35]). Conclusions: In a large cohort of outpatients with chronic HF with reduced EF, improvements in LVEF were common. Common baseline cardiac characteristics identified a population that was more likely to respond over time. These data may inform clinical decision making and should be the basis for future research on myocardial recovery.


Angiology ◽  
2020 ◽  
Vol 71 (5) ◽  
pp. 431-437
Author(s):  
Mohammad Zubaid ◽  
Wafa Rashed ◽  
Mustafa Ridha ◽  
Nooshin Bazargani ◽  
Adel Hamad ◽  
...  

We describe the characteristics of ambulatory patients with heart failure with reduced ejection fraction (HFrEF) in the Gulf region (Middle East) and the implementation of guideline-recommended treatments. We included 2427 HFrEF outpatients (mean age 59 ± 13 years, 75% males and median left ventricular ejection fraction [LVEF] of 30%). A high proportion of patients received guideline-recommended medications (angiotensin-converting enzyme inhibitor [ACEI]/angiotensin receptor blocker [ARB]/angiotensin receptor-neprilysin inhibitor [ARNI] 87%, β-blocker 91%, mineralocorticoid antagonist [MRA] 64%). However, only a minority of patients received guideline-recommended target doses (ACEI/ARB/ARNI 13%, β-blocker 27%, and MRA 4.4%). Old age was a significant independent predictor for not prescribing treatment ( P < .001 for ACEI/ARB/ARNI and MRA; and P = .002 for β-blockers). Other independent predictors were chronic kidney disease (for both ACEI/ARB/ARNI and MRA, P < .001) and higher LVEF ( P = .014 for β-blockers and P < .001 for MRA). Patients with HFrEF managed by heart failure specialists more often received recommended target doses of ACEI/ARB/ARNI (40% vs 11%, P < .001) and β-blockers (56% vs 26%, P < .001) compared to those treated by general cardiologists. Although the majority of our patients with HFrEF received guideline-recommended medications, the doses they were prescribed were suboptimal. Understanding the reasons behind this is important for improved practice.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Masuda ◽  
T Kanda ◽  
M Asai ◽  
T Mano ◽  
T Yamada ◽  
...  

Abstract Background The presence of atrial fibrillation (AF) has been demonstrated to be associated with poor clinical outcomes in heart failure patients with reduced ejection fraction. Objective This study aimed to elucidate the impact of the presence of atrial fibrillation (AF) on the clinical characteristics, therapeutics, and outcomes in patients with heart failure and preserved ejection fraction (HFpEF). Methods PURSUIT-HFpEF is a multicenter prospective observational study including patients hospitalized for acute heart failure with left ventricular ejection fraction of >50%. Patients with acute coronary syndrome or severe valvular disease were excluded. Results Of 486 HFpEF patients (age, 80.8±9.0 years old; male, 47%) from 24 cardiovascular centers, 199 (41%) had AF on admission. Patients with AF had lower systolic blood pressures (142±27 vs. 155±35mmHg, p<0.0001) and higher heart rates (91±29 vs. 82±26bpm, p<0.0001) than those without. There was no difference in the usage of inotropes or mechanical ventilation between the 2 groups. A higher quality of life score (EQ5D, 0.72±0.27 vs. 0.63±0.30, p=0.002) was observed at discharge in patients with than without AF. In addition, AF patients tended to demonstrate lower in-hospital mortality rates (0.5% vs. 2.4%, p=0.09) and shorter hospital stays (20.3±12.1 vs. 22.6±18.4 days, p=0.09) than those without. During a mean follow up of 360±111 days, mortality (14.1% vs. 15.3) and heart failure re-hospitalization rates (13.1% vs. 13.9%) were comparable between the 2 groups. Conclusion In contrast to heart failure patients with reduced ejection fraction, AF on admission was not associated with poor long-term clinical outcomes among HFpEF patients. Several in-hospital outcomes were better in patients with AF than in those without. Acknowledgement/Funding None


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