Anti-Inflammatory Therapy With Canakinumab for the Prevention of Hospitalization for Heart Failure
Abstract
Background: Subclinical inflammation is associated with an increased risk of heart failure and with adverse prognosis in patients with established heart failure. Yet, treatments specifically directed at reducing inflammation in patients with heart failure have not yet shown improved clinical outcomes. We tested the hypothesis that the interleukin-1β inhibitor canakinumab would prevent hospitalization for heart failure (HHF) and the composite of HHF or heart failure–related mortality. Methods: We randomized 10 061 patients with prior myocardial infarction and high-sensitivity C-reactive protein ≥2 mg/L to canakinumab 50, 150, or 300 mg or placebo, given subcutaneously once every 3 months. In total, 2173 (22%) reported a history of heart failure at baseline. We tested the hypothesis that canakinumab prevents prospectively collected HHF events and the composite of HHF or heart failure–related mortality. Results: A total of 385 patients had an HHF event during a median follow-up of 3.7 years. Patients who had HHF were older, had higher body mass index, and were more likely to have diabetes mellitus, hypertension, and prior coronary bypass surgery. As anticipated, median (quartile 1, 3) baseline concentrations of high-sensitivity C-reactive protein were higher among those who had HHF during follow-up than those who did not (5.7 [3.5, 9.9] mg/L versus 4.2 [2.8, 6.9] mg/L, respectively; P <0.0001). The unadjusted hazard ratios for HHF with each dose of canakinumab compared with placebo were 1.04 (95% CI, 0.79–1.36) for 50 mg, 0.86 (95% CI, 0.65–1.13) for 150 mg, and 0.76 (95% CI, 0.57–1.01) for 300 mg ( P for trend=0.025). The composite of HHF or heart failure–related mortality was also reduced by canakinumab, with unadjusted hazard ratios of 1.00 (95% CI, 0.78–1.29) for 50 mg, 0.88 (95% CI, 0.68–1.13) for 150 mg, and 0.78 (95% CI, 0.60–1.02) for 300 mg ( P for trend=0.042). Conclusions: These randomized double-blind placebo-controlled data suggest that therapy with canakinumab, an interleukin-1β inhibitor, is related to a dose-dependent reduction in HHF and the composite of HHF or heart failure–related mortality in a population of patients with prior myocardial infarction and elevations in high-sensitivity C-reactive protein. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01327846.
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An exploratory analysis of a clinical trial evaluating systemic administration of an IL1B neutralizing antibody for ischemic cardiac disease identified a reduction in heart failure hospitalization and heart-failure related mortality.
“an exploratory analysis of a clinical trial evaluating systemic administration of an IL1B neutralizing antibody for the treatment of ischemic cardiac disease36 identified a reduction in heart failure hospitalization and heart-failure related mortality37.”
From Chromatin remodelling drives immune cell–fibroblast communication in heart failure (2024) · cites this paper as [37]
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- Authors
- Everett, B. M., Cornel, J. H., Lainscak, M., Anker, S. D., Abbate, A., Thuren, T., Libby, P., Glynn, R. J., & Ridker, P. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Noordwest Ziekenhuisgroep (NL)
- Division of Cardiology, General Hospital Murska Sobota, and Faculty of Medicine, University of Ljubljana, Slovenia (M.L.).
- Berlin-Brandenburger Centrum für Regenerative Therapien (DE)
- Virginia Commonwealth University (US)
- Novartis (Switzerland) (CH)
- ORCID
- Venue
- Circulation
- Published
- 2019-03-05
- Volume
- 139
- Issue
- 10
- Pages
- 1289-1299
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2900002398
- Cited by
- 658
- References
- 33
- Citations by year
- 2026: 71 · 2025: 93 · 2024: 100 · 2023: 89 · 2022: 91 · 2021: 91 · 2020: 79 · 2019: 39 · 2018: 1 · 2012: 1
- FWCI
- 54.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- canakinumab, IL-1β inhibition, heart failure hospitalization, subclinical inflammation, high-sensitivity C-reactive protein, old myocardial infarction, anti-inflammatory therapy, cardiovascular risk reduction, dose-response relationship, diabetes mellitus, hypertension, body mass index, coronary artery disease, heart failure with reduced ejection fraction
- MeSH terms
- Aged, Anti-Inflammatory Agents, C-Reactive Protein, Dose-Response Relationship, Drug, Double-Blind Method, Female, Heart Failure, Humans, Male, Middle Aged, Patient Admission, Prospective Studies, Risk Factors, Time Factors, Biomarkers, Treatment Outcome, Disease Progression, Inflammation Mediators, Antibodies, Monoclonal, Humanized, Protective Factors
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