Successful treatment with ivabradine in a β‐blocker‐refractory patient with acute decompensated heart failure with reduced ejection fraction

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Abstract

Ivabradine is an established treatment for chronic heart failure with reduced ejection fraction (HFrEF); however, it is not used for acute heart failure treatment. Negative inotropic effects (NIE) often limit the up‐titration of β‐blockers. Contrarily, ivabradine has no NIE, and enables β‐blockers usage for treating patients with acute decompensated HFrEF.

Abstract

Inappropriate tachycardia is a symptom of acute heart failure and is often dealt with β‐blockers. However, β‐blocker up‐titration is challenging because of its negative inotropic effects. Thus, ivabradine is preferable over β‐blockers in such cases.

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Most cited references 19

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2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Paul A Heidenreich, Biykem Bozkurt, David Aguilar … (2022)

The “2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure” replaces the “2013 ACCF/AHA Guideline for the Management of Heart Failure” and the “2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.” The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure. A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients’ interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.

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Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study.

Karl Swedberg, Michel Komajda, Michael Christian Böhm … (2010)

Chronic heart failure is associated with high mortality and morbidity. Raised resting heart rate is a risk factor for adverse outcomes. We aimed to assess the effect of heart-rate reduction by the selective sinus-node inhibitor ivabradine on outcomes in heart failure. Patients were eligible for participation in this randomised, double-blind, placebo-controlled, parallel-group study if they had symptomatic heart failure and a left-ventricular ejection fraction of 35% or lower, were in sinus rhythm with heart rate 70 beats per min or higher, had been admitted to hospital for heart failure within the previous year, and were on stable background treatment including a β blocker if tolerated. Patients were randomly assigned by computer-generated allocation schedule to ivabradine titrated to a maximum of 7.5 mg twice daily or matching placebo. Patients and investigators were masked to treatment allocation. The primary endpoint was the composite of cardiovascular death or hospital admission for worsening heart failure. Analysis was by intention to treat. This trial is registered, number ISRCTN70429960. 6558 patients were randomly assigned to treatment groups (3268 ivabradine, 3290 placebo). Data were available for analysis for 3241 patients in the ivabradine group and 3264 patients allocated placebo. Median follow-up was 22.9 (IQR 18-28) months. 793 (24%) patients in the ivabradine group and 937 (29%) of those taking placebo had a primary endpoint event (HR 0.82, 95% CI 0.75-0.90, p<0.0001). The effects were driven mainly by hospital admissions for worsening heart failure (672 [21%] placebo vs 514 [16%] ivabradine; HR 0.74, 0.66-0.83; p<0.0001) and deaths due to heart failure (151 [5%] vs 113 [3%]; HR 0.74, 0.58-0.94, p=0.014). Fewer serious adverse events occurred in the ivabradine group (3388 events) than in the placebo group (3847; p=0.025). 150 (5%) of ivabradine patients had symptomatic bradycardia compared with 32 (1%) of the placebo group (p<0.0001). Visual side-effects (phosphenes) were reported by 89 (3%) of patients on ivabradine and 17 (1%) on placebo (p<0.0001). Our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure and confirm the important role of heart rate in the pathophysiology of this disorder. Servier, France. Copyright 2010 Elsevier Ltd. All rights reserved.

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Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.

Kim Fox, Ian Ford, P Gabriel Steg … (2008)

Ivabradine specifically inhibits the I(f) current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction. Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507. Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016). Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.

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Author and article information

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Keiji Matsunaga: matsunaga.keiji@kagawa-u.ac.jp

Journal

Journal ID (nlm-ta): Clin Case Rep

Journal ID (iso-abbrev): Clin Case Rep

Journal ID (doi): 10.1002/(ISSN)2050-0904

Journal ID (publisher-id): CCR3

Title: Clinical Case Reports

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2050-0904

Publication date (Electronic): 04 March 2023

Publication date Collection: March 2023

Volume: 11

Issue: 3 ( doiID: 10.1002/ccr3.v11.3 )

Electronic Location Identifier: e6890

Affiliations

[ ¹ ] Department of Cardiorenal and Cerebrovascular Medicine Faculty of Medicine Kagawa University Kagawa Japan

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[*] [* ] Correspondence

Keiji Matsunaga, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750‐1 Ikenobe, Mikicho, Kita‐gun, Kagawa 761‐0793, Japan.

Email: matsunaga.keiji@ 123456kagawa-u.ac.jp

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Tomoko Inoue https://orcid.org/0000-0001-5504-9352

Article

Publisher ID: CCR36890 Other ID: CCR3-2022-09-1939.R2

DOI: 10.1002/ccr3.6890

PMC ID: 9984869

PubMed ID: 36879680

SO-VID: 4c3e2b35-4567-4c63-8b3b-dbc7c70daa43

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This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

History

Date revision received : 12 December 2022

Date received : 14 September 2022

Date accepted : 03 January 2023

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Figures: 5, Tables: 0, Pages: 6, Words: 2656

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source-schema-version-number 2.0

cover-date March 2023

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.5 mode:remove_FC converted:04.03.2023

Keywords: acute decompensated heart failure,cancer therapy‐related cardiac dysfunction,inappropriate tachycardia,ivabradine,up‐titration,β‐blocker

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Keywords: acute decompensated heart failure, cancer therapy‐related cardiac dysfunction, inappropriate tachycardia, ivabradine, up‐titration, β‐blocker

Successful treatment with ivabradine in a β‐blocker‐refractory patient with acute decompensated heart failure with reduced ejection fraction

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Most cited references 19

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study.

Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.

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