scholarly journals Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Heart ◽  
2017 ◽  
Vol 104 (5) ◽  
pp. 407-415 ◽  
Author(s):  
Sean Lee Zheng ◽  
Fiona T Chan ◽  
Adam A Nabeebaccus ◽  
Ajay M Shah ◽  
Theresa McDonagh ◽  
...  

BackgroundClinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality.MethodsWe systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI.ResultsWe included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo.ConclusionThe efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Fu ◽  
A Uijl ◽  
F.W Dekker ◽  
L.H Lund ◽  
G Savarese ◽  
...  

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


2021 ◽  
Vol 12 ◽  
Author(s):  
Yaowang Lin ◽  
Meishan Wu ◽  
Bihong Liao ◽  
Xinli Pang ◽  
Qiuling Chen ◽  
...  

Beneficial effects of therapeutic drugs are controversial for heart failure with preserved ejection fraction (HFpEF). This meta-analysis aimed to evaluate and compare the interactive effects of different therapeutic drugs and placebo in patients with HFpEF. A comprehensive search was conducted using PubMed, Google Scholar, and Cochrane Central Register to identify related articles published before March 2021. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure (HF) hospitalization, and worsening HF events. A total of 14 randomized controlled trials, comprising 19,573 patients (intervention group, n = 9,954; control group, n = 9,619) were included in this network meta-analysis. All-cause mortality, cardiovascular mortality, and worsening HF events among therapeutic drugs and placebo with follow-up of 0.5–4 years were not found to be significantly correlated. The angiotensin receptor neprilysin inhibitor (ARNI) and angiotensin-converting enzyme inhibitor (ACEI) significantly reduced the HF hospitalizations compared with placebo (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.60–0.87 and HR 0.64, 95% CI 0.43–0.96, respectively), without heterogeneity among studies. The ARNI was superior to angiotensin receptor blocker (ARB) in reducing HF hospitalizations (HR 0.80, 95% CI 0.71–0.91), and vericiguat 10 mg ranked worse than beta-blockers for reducing all-cause mortality in patients with HFpEF (HR 3.76, 95% CI 1.06–13.32). No therapeutic drugs can significantly reduce mortality, but the ARNI or ACEI is associated with the low risk of HF hospitalizations for patients with HFpEF.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42021247034


2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Kentaro Kamiya ◽  
Yukihito Sato ◽  
Tetsuya Takahashi ◽  
Miyuki Tsuchihashi-Makaya ◽  
Norihiko Kotooka ◽  
...  

Background: Exercise-based cardiac rehabilitation (CR) improves health-related quality of life and exercise capacity in patients with heart failure (HF). However, CR efficacy in patients with HF who are elderly, frail, or have HF with preserved ejection fraction remains unclear. We examined whether participation in multidisciplinary outpatient CR is associated with long-term survival and rehospitalization in patients with HF, with subgroup analysis by age, sex, comorbidities, frailty, and HF with preserved ejection fraction. Methods: This multicenter retrospective cohort study was performed in patients hospitalized for acute HF at 15 hospitals in Japan, 2007 to 2016. The primary outcome (composite of all-cause mortality and HF rehospitalization after discharge) and secondary outcomes (all-cause mortality and HF rehospitalization) were analyzed in outpatient CR program participants versus nonparticipants. Results: Of the 3277 patients, 26% (862) participated in outpatient CR. After propensity matching for potential confounders, 1592 patients were included (n=796 pairs), of which 511 had composite outcomes (223 [14%] all-cause deaths and 392 [25%] HF rehospitalizations, median 2.4-year follow-up). Hazard ratios associated with CR participation were 0.77 (95% CI, 0.65–0.92) for composite outcome, 0.67 (95% CI, 0.51–0.87) for all-cause mortality, and 0.82 (95% CI, 0.67–0.99) for HF-related rehospitalization. CR participation was also associated with numerically lower rates of composite outcome in patients with HF with preserved ejection fraction or frail patients. Conclusions: Outpatient CR participation was associated with substantial prognostic benefit in a large HF cohort regardless of age, sex, comorbidities, frailty, and HF with preserved ejection fraction.


2018 ◽  
Vol 131 (12) ◽  
pp. 1473-1481 ◽  
Author(s):  
Phillip H. Lam ◽  
Neha Gupta ◽  
Daniel J. Dooley ◽  
Steven Singh ◽  
Prakash Deedwania ◽  
...  

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.


BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e044605
Author(s):  
Shiro Hoshida ◽  
Koichi Tachibana ◽  
Yukinori Shinoda ◽  
Tomoko Minamisaka ◽  
Takahisa Yamada ◽  
...  

ObjectivesThe severity of diastolic dysfunction is assessed using a combination of several indices of left atrial (LA) volume overload and LA pressure overload. We aimed to clarify which overload is more associated with the prognosis in patients with heart failure and preserved ejection fraction (HFpEF).SettingA prospective, multicenter observational registry of collaborating hospitals in Osaka, Japan.ParticipantsWe enrolled hospitalised patients with HFpEF showing sinus rhythm (men, 79; women, 113). Blood tests and transthoracic echocardiography were performed before discharge. The ratio of diastolic elastance (Ed) to arterial elastance (Ea) was used as a relative index of LA pressure overload.Primary outcome measuresAll-cause mortality and admission for heart failure were evaluated at >1 year after discharge.ResultsIn the multivariable Cox regression analysis, Ed/Ea, but not LA volume index, was significantly associated with all-cause mortality or admission for heart failure (HR 2.034, 95% CI 1.059 to 3.907, p=0.032), independent of age, sex, and the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level. In patients with a higher NT-proBNP level, the effect of higher Ed/Ea on prognosis was prominent (p=0.015).ConclusionsEd/Ea, an index of LA pressure overload, was significantly associated with the prognosis in elderly patients with HFpEF showing sinus rhythm.Trial registration numberUMIN000021831.


2021 ◽  
Vol 8 ◽  
Author(s):  
Sunying Wang ◽  
Yuwei Wang ◽  
Manqing Luo ◽  
Kaiyang Lin ◽  
Xiaoxu Xie ◽  
...  

Aim: Accumulating evidence suggests that MELD-XI score holds the ability to predict the prognosis of congestive heart failure. However, most of the evidence is based on the end-stage heart failure population; thus, we aim to explore the association between the MELD-XI score and the prognosis in heart failure with preserved ejection fraction (HFpEF).Methods: A total of 30,096 patients hospitalized for HFpEF in Fujian Provincial Hospital between January 1, 2014 and July 17, 2020 with available measures of creatinine and liver function were enrolled. The primary endpoint was 60-day in-hospital all-cause mortality. Secondary endpoints were 60-day in-hospital cardiovascular mortality and 30-day rehospitalization for heart failure.Results: A total of 222 patients died within 60 days after admission, among which 75 deaths were considered cardiogenic. And 73 patients were readmitted for heart failure within 30 days after discharge. Generally, patients with an elevated MELD-XI score tended to have more comorbidities, higher NYHA class, and higher inflammatory biomarkers levels. Meanwhile, the MELD-XI score was positively correlated with NT-pro BNP, left atrial diameter, E/e' and negatively correlated with LVEF. After adjusting for conventional risk factors, the MELD-XI score was independently associated with 60-day in-hospital all-cause mortality [hazard ratio(HR) = 1.052, 95% confidential interval (CI) 1.022–1.083, P = 0.001], 60-day in-hospital cardiovascular mortality (HR = 1.064, 95% CI 1.013–1.118, P = 0.014), and 30-day readmission for heart failure (HR = 1.061, 95% CI 1.015–1.108, P = 0.009). Furthermore, the MELD-XI score added an incremental discriminatory capacity to risk stratification models developed based on this cohort.Conclusion: The MELD-XI score was associated with short-term adverse events and provided additional discriminatory capacity to risk stratification models in patients hospitalized for HFpEF.


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