Effects of Ivabradine on Cardiac Remodeling in Patients With Stable Symptomatic Heart Failure: A Systematic Review and Meta-analysis

Wan, Hongbing; Huang, Tieqiu; Zhang, Hongzhou; Wu, Qinghua

doi:10.1016/j.clinthera.2020.10.005

Cited by 5 publications

(6 citation statements)

References 40 publications

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“…However, our meta‐analysis included two RCTs and one subgroup analysis favors adding Ivabradine for reverse remodeling in chronic HFrEF patients 21,24,26 . This finding was in accordance with Wan H, et al's study, 35 which demonstrated Ivabradine had a positive association with reverse cardiac remodeling (LVESVI; MD = −7.30; 95%CI ‐12.94, −1.66; LVEDVI; MD = −7.27; 95%CI ‐14.04, −0.50). Several studies hypothesized the potential mechanisms associated with Ivabradine improving cardiac remodeling were the modification in cardiac myocyte function, optimization of energy consumption, improvement of endothelial function, a reversal in electrophysiological changes, to the extent of reduction of RAAS stimulation and sympathetic drive etc 40 .…”

Section: Discussionsupporting

confidence: 89%

“…Second, we reconfirmed the neutral effect of Ivabradine on cardiovascular mortality in chronic HFrEF patients, although it could improve LVEF. Moreover, we systematically evaluated the safety and efficiency with clinical events, echocardiographic parameters, exercise tolerance and QoL scores while other meta‐analyses mainly focused on some specific issues such as HR changes, 31,32 cardiac remodeling, 35 diastolic dysfunction 30 or the safety of Ivabradine 29,31 …”

Section: Discussionmentioning

confidence: 99%

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Impact of ivabradine on the cardiac function of chronic heart failure reduced ejection fraction: Meta‐analysis of randomized controlled trials

Sasmita

Huang

Liu

et al. 2021

Clinical Cardiology

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Elevated resting heart rate in chronic heart failure (HF) patients has been associated with higher mortality and poor prognosis. Ivabradine is a new pure bradycardic agent that has been used to treat angina or heart failure reduced ejection fraction (HFrEF) with sinus heart rate above 70 beats per minute. However, the effect of ivabradine for chronic HF patients on rehospitalization and cardiac function is still inconsistent. Thus, this meta‐analysis aimed to elucidate the effect of Ivabradine in chronic HFrEF patients. We systematically searched PubMed, Medline, Clinical http://trials.gov, and The Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) of ivabradine with search terms Ivabradine (MeSH Terms), chronic heart failure and beta‐blocker. The primary endpoints of the study include the impact of Ivabradine on heart rate, left ventricle ejection fraction (LVEF), left ventricular remodeling, exercise capacity, and quality of life (QoL) in patients with chronic HFrEF. Secondary endpoints were safety analysis of Ivabradine including cardiovascular mortality, worsening HF readmission, visual disturbances, and asymptomatic bradycardia. The analysis was done by Review Manager 5.4 Analyzer, to analyze the mean differences (MD) for continuous data and risks ratio (RR) for dichotomous data. A total of six RCTs and one subgroup analysis showed add of Ivabradine to standard HF therapy was associated with greater resting heart rate reduction (MD = −9.57; 95% CI ‐11.15, −8.00), improved LVEF (MD = 3.89; 95% CI 2.61, 5.17), left ventricular reverse remodeling improvement (MD = −3.73; 95% CI ‐4.25, −3.21, LVESV; MD = −17.00, 95%CI ‐29.65, −4.35, LVEDD; MD = −1.43, 95%CI ‐2.78, −0.08, LVEDV; MD = −14.75, 95%CI ‐34.36, 4.87), increased exercise capacity (exercise duration; MD = 8.52; 95%CI 0.09, 16.94), and significant reduction on rehospitalization due to worsening HF (RR = 0.76, 95%CI 0.69, 0.84). However, Ivabradine has no significant effect on the quality of life (MD = 0.65; 95%CI ‐10.52, 11.82), and cardiovascular mortality (RR = 0.92; 95%CI 0.82, 1.03). Moreover, there were some events of visual disturbances and asymptomatic bradycardia observed in the Ivabradine group compared to the placebo group (RR = 4.76; 95%CI 3.03, 7.48; RR = 3.78; 95%CI 2.77, 5.15, respectively). Addition of Ivabradine to standard HF therapy is associated with cardiac function improvement, reduction on worsening HF readmission, greater HR reduction, and better exercise capacity in chronic HFrEF patients, although it cannot reduce cardiovascular mortality or improve the quality of life.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Impact of ivabradine on the cardiac function of chronic heart failure reduced ejection fraction: Meta‐analysis of randomized controlled trials

Sasmita

Huang

Liu

et al. 2021

Clinical Cardiology

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“…Ivabradine is not considered the first option in the case of acute HF, cardiogenic shock or acute myocardial infarction. However, its use in other contexts (chronic HF and chronic ischemic heart disease) determines an improvement in cardiac oxygenation and wall stress of the myocardium, due to a dose-dependent reduction in HR at rest and during exercise, 18,19 with no effects on left ventricle contraction. 15 These properties suggest that ivabradine may play a role also in the treatment of acute HF.…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic effects of heart rate lowering in patients admitted for acute heart failure: the RedRate-HF Study (Reduction of heart Rate in Heart Failure)

Mortara¹,

Rossi²,

Mazzetti³

et al. 2023

Journal of Cardiovascular Medicine

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Background In patients admitted for acute heart failure (HF) indication for drugs which reduce the heart rate (HR) is debated. The multicentre prospective study Reduction of heart Rate in Heart Failure (RedRate-HF) was designed to analyse the hemodynamic effects of an early reduction of HR in acute HF. Methods Hemodynamic parameters were recorded by using the bioimpedance technique, which was shown to be accurate, highly reproducible and sensitive to intra-observer changes. Lowering HR was obtained by ivabradine 5 mg bd, given 48–72 h after admission on the top of optimized treatment. Patients were followed at 24, 48, 72 h after drug assumption and at hospital discharge. Results Twenty patients of a mean age of 67 ± 15 years, BNP at entry 1348 ± 1198 pg/ml were enrolled. Despite a clinical stabilization, after 48–72 h from admission, HR was persistently >70 bpm. Ivabradine was well tolerated in all patients with a significant increase in RR interval from 747 ± 69 ms at baseline to 948 ± 121 ms at discharge, P < 0.0001. Change in HR was associated with a significant increase in stroke volume (baseline 73 ± 22 vs. 84 ± 19 ml at discharge, P = 0.03), and reduction in left cardiac work index (baseline 3.6 ± 1.2 vs. 3.1 ± 1.1 kg/m2 at discharge, P = 0.04). Other measures of heart work were also significantly affected while cardiac output remained unchanged Conclusion The strategy of an early lowering of HR in patients admitted for acute HF on top of usual care is feasible and safe. The HR reduction causes a positive increase in stroke volume and may contribute to saving energy without affecting cardiac output.

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“…11 Subsequent studies showed significant improvement in the New York Heart Association functional class, quality of life, and left ventricular remodeling with ivabradine. 12,13 Based on these results, ivabradine has been included in the current guidelines for chronic HFrEF management. 5,6 According to the health insurance system regulation, ivabradine's use is confined to HFrEF patients who either have contraindications to or exhibit intolerance toward β-blockers.…”

Section: Introductionmentioning

confidence: 99%

“…The SHIFT trial (Systolic Heart Failure Treatment with the I(f) Inhibitor Ivabradine Trial) demonstrated an 18% relative risk reduction in the primary endpoint of cardiovascular death or hospitalization for worsening HF with ivabradine compared with placebo 11 . Subsequent studies showed significant improvement in the New York Heart Association functional class, quality of life, and left ventricular remodeling with ivabradine 12,13 . Based on these results, ivabradine has been included in the current guidelines for chronic HFrEF management 5,6 …”

Section: Introductionmentioning

confidence: 99%

Evaluating the applicability of ivabradine in acute heart failure

Tsai,

Chen

et al. 2023

Clinical Cardiology

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BackgroundWhile ivabradine has demonstrated benefits in heart rate control and prognosis for chronic heart failure patients, its application in acute decompensated heart failure remains underexplored.HypothesisFor patients with acute decompensated heart failure with reduced ejection fraction (HFrEF) who are intolerant to β‐blockers or unable to further titrate their dosage, the use of ivabradine is hypothesized to be effective and safe is improving outcomes.MethodsThis retrospective, multicenter database analysis included patients with hospitalized decompensated heart failure with a left ventricular ejection fraction of ≤40% from June 1, 2015 to December 31, 2020. The exclusion criteria were a baseline heart rate of <70 bpm, previous use of ivabradine, mortality during admission, existing atrial fibrillation, or atrial flutter. The primary outcome was the composite of cardiovascular death and hospitalization for heart failure.ResultsOf the 4163 HFrEF patients analyzed, 684 (16.4%) were administered ivabradine during their index admission. After matching, there were 617 patients in either group. The results indicated that ivabradine use was not significantly associated with the risk of the primary composite outcome (hazard ratio: 1.10; 95% confidence interval: 0.94−1.29). Similarly, the risk of secondary outcomes and adverse renal events did not significantly differ between the ivabradine and non‐ivabradine cohorts (all p > .05).ConclusionFor hospitalized acute decompensated heart failure patients who are intolerant to β‐blockers or cannot further titrate them, ivabradine offers a consistent therapeutic effect. No significant disparities were noted between the ivabradine and non‐ivabradine groups in heart failure hospitalization and cardiovascular death.

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Effects of Ivabradine on Cardiac Remodeling in Patients With Stable Symptomatic Heart Failure: A Systematic Review and Meta-analysis

Cited by 5 publications

References 40 publications

Impact of ivabradine on the cardiac function of chronic heart failure reduced ejection fraction: Meta‐analysis of randomized controlled trials

Impact of ivabradine on the cardiac function of chronic heart failure reduced ejection fraction: Meta‐analysis of randomized controlled trials

Hemodynamic effects of heart rate lowering in patients admitted for acute heart failure: the RedRate-HF Study (Reduction of heart Rate in Heart Failure)

Evaluating the applicability of ivabradine in acute heart failure

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