Association Between β-Blocker Use and Mortality/Morbidity in Patients With Heart Failure With Reduced, Midrange, and Preserved Ejection Fraction and Advanced Chronic Kidney Disease

Background: It is unknown if β-blockers reduce mortality/morbidity in patients with heart failure (HF) and advanced chronic kidney disease (CKD), a population underrepresented in HF trials. Methods: Observational cohort of HF patients with advanced CKD (estimated glomerular filtration rate <30 mL/min per 1.73 m 2 ) from the Swedish Heart Failure Registry between 2001 and 2016. We first explored associations between β-blocker use, 5-year death, and the composite of cardiovascular death/HF hospitalization among 3775 patients with HF with reduced ejection fraction (HFrEF) and advanced CKD. We compared observed hazards with those from a control cohort of 15 346 patients with HFrEF and moderate CKD (estimated glomerular filtration rate <60–30 mL/min per 1.73 m 2 ), for whom β-blocker trials demonstrate benefit. Second, we explored outcomes associated to β-blocker among advanced CKD participants with preserved (HFpEF; N=2009) and midrange ejection fraction (HFmrEF; N=1514). Results: During a median follow-up of 1.3 years, 2012 patients had a subsequent HF hospitalization, and 2849 died in the HFrEF cohort, of which 2016 died due to cardiovascular causes. Among patients with HFrEF, β-blocker use was associated with lower risk of death (adjusted hazard ratio 0.85 [95% CI, 0.75–0.96]) and cardiovascular mortality/HF hospitalization (0.87 [0.77–0.98]) compared with nonuse. The magnitude of the associations was similar to that observed for HFrEF patients with moderate CKD. Conversely, no significant association was observed for β-blocker users in advanced CKD with HFpEF (death: 0.88 [0.77–1.02], cardiovascular mortality/HF hospitalization: 1.05 [0.90–1.23]) or HFmrEF (death: 0.95 [0.79–1.14], cardiovascular mortality/HF hospitalization: 1.09 [0.90–1.31]). Conclusions: In HFrEF patients with advanced CKD, the use of β-blockers was associated with lower morbidity and mortality. Although inconclusive due to limited power, these benefits were not observed in similar patients with HFpEF or HFmrEF.

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SO057BETA-BLOCKERS ARE ASSOCIATED WITH REDUCED MORTALITY IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION AND ADVANCED CHRONIC KIDNEY DISEASE: COHORT STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa139.so057 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Edouard L Fu ◽

Alicia Uijl ◽

Friedo W Dekker ◽

Lars H Lund ◽

Gianluigi Savarese ◽

...

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Ejection Fraction ◽

Beta Blocker ◽

Beta Blockers ◽

Advanced Chronic Kidney Disease ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

All Cause Mortality

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.

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Acute declines in estimated glomerular filtration rate on enalapril and mortality and cardiovascular outcomes in patients with heart failure with reduced ejection fraction

Kidney International ◽

10.1016/j.kint.2019.05.019 ◽

2019 ◽

Vol 96 (5) ◽

pp. 1185-1194 ◽

Cited By ~ 6

Author(s):

Wendy McCallum ◽

Hocine Tighiouart ◽

Elaine Ku ◽

Deeb Salem ◽

Mark J. Sarnak

Keyword(s):

Heart Failure ◽

Glomerular Filtration Rate ◽

Ejection Fraction ◽

Glomerular Filtration ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Cardiovascular Outcomes ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure

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Implementation of Guideline-Recommended Therapies for Patients With Heart Failure and Reduced Ejection Fraction: A Regional Arab Middle East Experience

Angiology ◽

10.1177/0003319720905742 ◽

2020 ◽

Vol 71 (5) ◽

pp. 431-437

Author(s):

Mohammad Zubaid ◽

Wafa Rashed ◽

Mustafa Ridha ◽

Nooshin Bazargani ◽

Adel Hamad ◽

...

Keyword(s):

Heart Failure ◽

Middle East ◽

Ejection Fraction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Angiotensin Receptor ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

Β Blocker ◽

Β Blockers

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.

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The association of beta-blocker use with mortality in elderly patients with congestive heart failure and advanced chronic kidney disease

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz167 ◽

2019 ◽

Vol 35 (5) ◽

pp. 782-789 ◽

Cited By ~ 6

Author(s):

Amber O Molnar ◽

William Petrcich ◽

Matthew A Weir ◽

Amit X Garg ◽

Michael Walsh ◽

...

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Congestive Heart Failure ◽

Kidney Disease ◽

Elderly Patients ◽

Randomized Trials ◽

Advanced Chronic Kidney Disease ◽

All Cause Mortality ◽

Β Blocker ◽

Β Blockers

Abstract Background Whether the survival benefit of β-blockers in congestive heart failure (CHF) from randomized trials extends to patients with advanced chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 but not receiving dialysis] is uncertain. Methods This was a retrospective cohort study using administrative datasets. Older adults from Ontario, Canada, with incident CHF (median age 79 years) from April 2002 to March 2014 were included. We matched new users of β-blockers to nonusers on age, sex, eGFR categories (>60, 30–60, <30), CHF diagnosis date and a high-dimensional propensity score. Using Cox proportional hazards models, we examined the association of β-blocker use versus nonuse with all-cause mortality. Results We matched 5862 incident β-blocker users (eGFR >60, n = 3136; eGFR 30–60, n = 2368; eGFR <30, n = 358). There were 2361 mortality events during follow-up. β-Blocker use was associated with reduced all-cause mortality [adjusted hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.54–0.64]. This result was consistent across all eGFR categories (>60: adjusted HR 0.55, 95% CI 0.49–0.62; 30–60: adjusted HR 0.63, 95% CI 0.55–0.71; <30: adjusted HR 0.55, 95% CI 0.41–0.73; interaction term, P = 0.30). The results were consistent in an intention-to-treat analysis and with β-blocker use treated as a time-varying exposure. Conclusions β-Blocker use is associated with reduced all-cause mortality in elderly patients with CHF and CKD, including those with an eGFR <30. Randomized trials that examine β-blockers in patients with CHF and advanced CKD are needed.

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Association between use of beta-blockers and mortality/morbidity in patients with heart failure with reduced, midrange or preserved ejection fraction and advanced chronic kidney disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.1045 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

E Fu ◽

A Uijl ◽

F.W Dekker ◽

L.H Lund ◽

G Savarese ◽

...

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Ejection Fraction ◽

Beta Blocker ◽

Beta Blockers ◽

Preserved Ejection Fraction ◽

Advanced Chronic Kidney Disease ◽

Patients With Heart Failure ◽

All Cause Mortality

Abstract Background 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. Purpose We evaluated if beta-blockers are associated with improved survival and cardiovascular outcomes in patients with HFrEF and advanced CKD, and if potential benefits of beta-blockers would extend also to HFpEF and HFmrEF with advanced CKD. Methods 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. We did not exclude patients with atrial fibrillation. 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). Analyses were repeated in individuals with HF with preserved ejection fraction (HFpEF; EF ≥50%) or midrange ejection fraction (HFmrEF; EF 40–49%). Results In HFrEF and advanced CKD, 89% received beta-blockers. Overall, median (IQR) age was 81 (74–86) years, 36% were women and median eGFR was 26 (20–28) ml/min/1.73m2. During a median of 1.3 years 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 [all-cause mortality: 0.85 (95% CI 0.78–0.91); CV mortality/HF hospitalization: 0.88 (95% CI 0.82–0.96)]. Adjusted HRs were 0.88 (95% CI 0.77–1.02) and 1.07 (95% CI 0.92–1.24) for individuals with HFpEF and advanced CKD and 0.95 (95% CI 0.80–1.13) and 1.13 (95% CI 0.94–1.36) for individuals with HFmrEF and advanced CKD, for all-cause mortality and CV mortality/HF hospitalization, 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. However, these benefits were not observed in patients with HFpEF or HFmrEF with severe CKD. Funding Acknowledgement Type of funding source: None

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Estimated Glomerular Filtration Rate Is Associated With an Increased Risk of Death in Heart Failure Patients With Preserved Ejection Fraction

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.643358 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhuo Chen ◽

Qian Lin ◽

Jingen Li ◽

Xinyi Wang ◽

Jianqing Ju ◽

...

Keyword(s):

Heart Failure ◽

Glomerular Filtration Rate ◽

Ejection Fraction ◽

Glomerular Filtration ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Cardiovascular Death ◽

Preserved Ejection Fraction ◽

Increased Risk ◽

Patients With Heart Failure

Background: Renal dysfunction is associated with adverse cardiovascular outcomes in patients with heart failure (HF), but its impact on patients with heart failure with preserved ejection fraction (HFpEF) remains unclear.Methods: 3,392 subjects of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial were assigned to two groups by estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 or 30–59 ml/min/1.73 m2. The outcomes, including all-cause death, cardiovascular death and HF hospitalization, were examined by multivariable cox models.Results: Over a median follow-up of 3.4 ± 1.7 years, a total of 524 all-cause deaths, 334 cardiovascular deaths and 440 HF hospitalizations occurred. Compared with patients with eGFR ≥ 60 ml/min/1.73 m2, those with eGFR 30–59 ml/min/1.73 m2 were associated with an increased risk of the all-cause death [adjusted hazard ratio (HR), 1.47; 95% confidence interval (CI), 1.24–1.76; P < 0.001], cardiovascular death (adjusted HR, 1.53; 95% CI: 1.23–1.91; p < 0.001), and HF hospitalization (adjusted HR: 1.21; 95% CI: 1.00–1.47; p = 0.049) after multivariable adjustment for potential confounders.Conclusions: eGFR 30–59 ml/min/1.73 m2 was related to an increased risk of all-cause death, cardiovascular death and HF hospitalization in HFpEF patients.

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