Comparison of Pharmacological Treatment Effects on Long-Time Outcomes in Heart Failure With Preserved Ejection Fraction: A Network Meta-analysis of Randomized Controlled Trials

Lin, Yaowang; Wu, Minna; Liao, Bihong; Pang, Xinli; Chen, Qiuling; Yuan, Jie; Dong, Shaohong

doi:10.3389/fphar.2021.707777

Cited by 8 publications

(13 citation statements)

References 31 publications

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“…A previous network meta-analysis demonstrated that, for patients with HF and an LVEF of 40% or more, ARNIs and ACE inhibitors were associated with a significant decrease in the risk of hospital admission for HF, but MRAs were not. 14 These results are partly inconsistent with the results of our analysis. In the previous analysis, a positive result of an ACE inhibitor trial during the first year, rather than a negative result during the entire follow-up, was extracted, 15 and a result of cardiac hospitalization in an MRA trial was extracted as a result of HF hospitalization.…”

Section: Discussioncontrasting

confidence: 82%

Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction

Xiang

Zhang

et al. 2022

JAMA Netw Open

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ImportanceIn recent years, significant progress has been made in the pharmacologic treatment of heart failure (HF) with reduced ejection fraction (HFrEF), but there is still insufficient evidence for drug therapy for HF with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF).ObjectiveTo compare the outcomes associated with different drug combinations for the treatment of HFpEF and HFmrEF.Data SourcesA search of the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was conducted for studies published from inception to October 9, 2021.Study SelectionRandomized clinical trials on the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), β-blockers, and sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with HFpEF or HFmrEF.Data Extraction and SynthesisData extraction and bias assessment were independently performed by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. All data for 3 outcomes were pooled with a fixed-effect model.Main Outcomes and MeasuresThe main outcomes were first hospitalization for HF, all-cause mortality, and cardiovascular mortality. Hazard ratios (HRs) and 95% credible intervals (CrIs) were evaluated using a bayesian network meta-analysis model.ResultsIn this analysis, 19 randomized clinical trials, including 20 633 patients with HF and an ejection fraction of 40% or more, without a remarkable risk of bias were included. Compared with placebo, no treatments were associated with a significant reduction in the risk of all-cause death or cardiovascular death. SGLT2 inhibitors, ARNIs, and MRAs were associated with a significant decrease in the risk of HF hospitalization compared with placebo (SGLT2 inhibitors: HR, 0.71 [95% CrI, 0.60-0.83]; ARNIs: HR, 0.76 [95% CrI, 0.61-0.95]; MRAs: HR, 0.83 [95% CrI, 0.69-0.99]), and SGLT2 inhibitors were the optimal drug class in terms of reducing the risk for HF admission. Sensitivity analysis results demonstrated a progressive decrease in the risk of HF admission and an advance in mean rank associated with the increasing use of drug classes.Conclusions and RelevanceThe findings of this study suggest that SGLT2 inhibitors were the optimal drug class for HFpEF and HFmrEF, consistent with the most recent guideline recommendation. The incremental use of combinations of SGLT2 inhibitors, ACE inhibitors or ARBs, and β-blockers may be associated with accumulative benefits in HF hospitalization rather than all-cause death among patients with HFpEF and HFmrEF.

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Section: Discussioncontrasting

confidence: 82%

Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction

Xiang

Zhang

et al. 2022

JAMA Netw Open

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“…In a meta-analysis (Khan et al, 2017) higher doses of ACEi or ARB significantly though modestly improved the composite end point of all-cause mortality or HF associated hospitalizations. This finding is supported by recent metaanalysis comparing the impact of ACEi, ARB, beta-blockers and the sGC stimulator vericiguat on all-cause mortality and HF associated need for hospitalization in HFpEF patients (Lin et al, 2021). The meta-analysis included 14 randomized trials.…”

Section: Therapeutic Options In Hfpef Between Facts and Beliefmentioning

confidence: 67%

Current Understanding of Molecular Pathophysiology of Heart Failure With Preserved Ejection Fraction

et al. 2022

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Heart Failure (HF) is the most common cause of hospitalization in the Western societies. HF is a heterogeneous and complex syndrome that may result from any dysfunction of systolic or diastolic capacity. Abnormal diastolic left ventricular function with impaired relaxation and increased diastolic stiffness is characteristic of heart failure with preserved ejection fraction (HFpEF). HFpEF accounts for more than 50% of all cases of HF. The prevalence increases with age: from around 1% for those aged <55 years to >10% in those aged 70 years or over. Nearly 50% of HF patients have HFrEF and the other 50% have HFpEF/HFmrEF, mainly based on studies in hospitalized patients. The ESC Long-Term Registry, in the outpatient setting, reports that 60% have HFrEF, 24% have HFmrEF, and 16% have HFpEF. To some extent, more than 50% of HF patients are female. HFpEF is closely associated with co-morbidities, age, and gender. Epidemiological evidence suggests that HFpEF is highly represented in older obese women and proposed as ‘obese female HFpEF phenotype’. While HFrEF phenotype is more a male phenotype. In addition, metabolic abnormalities and hemodynamic perturbations in obese HFpEF patients appear to have a greater impact in women then in men (Sorimachi et al., European J of Heart Fail, 2022, 22). To date, numerous clinical trials of HFpEF treatments have produced disappointing results. This outcome suggests that a “one size fits all” approach to HFpEF may be inappropriate and supports the use of tailored, personalized therapeutic strategies with specific treatments for distinct HFpEF phenotypes. The most important mediators of diastolic stiffness are the cardiomyocytes, endothelial cells, and extracellular matrix (ECM). The complex physiological signal transduction networks that respond to the dual challenges of inflammatory and oxidative stress are major factors that promote the development of HFpEF pathologies. These signalling networks contribute to the development of the diseases. Inhibition and/or attenuation of these signalling networks also delays the onset of disease. In this review, we discuss the molecular mechanisms associated with the physiological responses to inflammation and oxidative stress and emphasize the nature of the contribution of most important cells to the development of HFpEF via increased inflammation and oxidative stress.

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“…Hence, medications focused on this pathway will not improve mortality as RAAS activity is lower in HFpEF. Instead, the pathophysiology of HFpEF is primarily driven by tissue congestion brought on by elevated heart-filling pressures [ 29 ].…”

Section: Reviewmentioning

confidence: 99%

The Efficacy of Various Pharmacological Agents on Long-Term Outcomes in Patients With Heart Failure With Preserved Ejection Fraction: A Meta-Analysis of Randomized Control Trials

Faisal¹,

Ganaie²,

Batool³

et al. 2022

Cureus

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The beneficial impacts of various drugs on long-term outcomes in patients with heart failure with preserved ejection fraction (HFpEF) have been a matter of controversy. The aim of this meta-analysis was to systematically review randomized control trials (RCTs) involving patients with heart failure with preserved left ventricular ejection fraction (LVEF) and identify the effects of various treatment options [angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, angiotensin receptor blockers, and aldosterone receptor blockers] on all-cause mortality, cardiovascular mortality, and hospitalization due to cardiovascular reasons. The current meta-analysis has been conducted as per the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed without any restrictions on language by using the electronic databases Cochrane Library, EMBASE, and PubMed up to July 20, 2022. The outcomes assessed in this meta-analysis included all-cause mortality, cardiovascular mortality, and hospitalization due to cardiovascular reasons. Overall, 10 articles were included in the current meta-analysis with a pooled sample size of 13,336 patients with HFpEF. In comparison to the placebo, among all four pharmacological agents, beta-blockers were the only agent that decreased the risk of all-cause mortality and cardiovascular outcomes. On the other hand, a significant reduction in hospitalization due to cardiac-related reasons was reported in patients on ACE inhibitors as compared to placebo. No other pharmacological agent had an impact on hospitalization due to cardiacrelated reasons. The current meta-analysis indicates the possible benefits of beta-blockers in HFpEF in terms of reducing cardiovascular death and all-cause mortality.

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Comparison of Pharmacological Treatment Effects on Long-Time Outcomes in Heart Failure With Preserved Ejection Fraction: A Network Meta-analysis of Randomized Controlled Trials

Cited by 8 publications

References 31 publications

Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction

Optimal Pharmacologic Treatment of Heart Failure With Preserved and Mildly Reduced Ejection Fraction

Current Understanding of Molecular Pathophysiology of Heart Failure With Preserved Ejection Fraction

The Efficacy of Various Pharmacological Agents on Long-Term Outcomes in Patients With Heart Failure With Preserved Ejection Fraction: A Meta-Analysis of Randomized Control Trials

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