Interleukin-1 Blockade With Anakinra to Prevent Adverse Cardiac Remodeling After Acute Myocardial Infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot Study)
Acute myocardial infarction (AMI) initiates an intense inflammatory response in which interleukin-1 (IL-1) plays a central role. The IL-1 receptor antagonist is a naturally occurring antagonist, and anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot st...
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| Veröffentlicht in: | The American journal of cardiology 2010-05, Vol.105 (10), p.1371-1377.e1 |
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| creator | Abbate, Antonio, MD, PhD Kontos, Michael C., MD Grizzard, John D., MD Biondi-Zoccai, Giuseppe G.L., MD Van Tassell, Benjamin W., PharmD Robati, Roshanak, MD Roach, Lenore M., RN Arena, Ross A., PhD Roberts, Charlotte S., ACNP Varma, Amit, MD Gelwix, Christopher C., MD Salloum, Fadi N., PhD Hastillo, Andrea, MD Dinarello, Charles A., MD Vetrovec, George W., MD |
| description | Acute myocardial infarction (AMI) initiates an intense inflammatory response in which interleukin-1 (IL-1) plays a central role. The IL-1 receptor antagonist is a naturally occurring antagonist, and anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot study was to test the safety and effects of IL-1 blockade with anakinra on left ventricular (LV) remodeling after AMI. Ten patients with ST-segment elevation AMI were randomized to either anakinra 100 mg/day subcutaneously for 14 days or placebo in a double-blind fashion. Two cardiac magnetic resonance (CMR) imaging and echocardiographic studies were performed during a 10- to 14-week period. The primary end point was the difference in the interval change in the LV end-systolic volume index (LVESVi) between the 2 groups on CMR imaging. The secondary end points included differences in the interval changes in the LV end-diastolic volume index, and C-reactive protein levels. A +2.0 ml/m2 median increase (interquartile range +1.0, +11.5) in the LVESVi on CMR imaging was seen in the placebo group and a −3.2 ml/m2 median decrease (interquartile range −4.5, −1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m2 . On echocardiography, the median difference in the LVESVi change was 13.4 ml/m2 (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m2 , p = 0.033) and echocardiography (9.4 ml/m2 , p = 0.008). The change in C-reactive protein levels between admission and 72 hours after admission correlated with the change in the LVESVi (R = +0.71, p = 0.022). In conclusion, in the present pilot study of patients with ST-segment elevation AMI, IL-1 blockade with anakinra was safe and favorably affected by LV remodeling. If confirmed in larger trials, IL-1 blockade might represent a novel therapeutic strategy to prevent heart failure after AMI. |
| doi_str_mv | 10.1016/j.amjcard.2009.12.059 |
| format | Article |
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The IL-1 receptor antagonist is a naturally occurring antagonist, and anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot study was to test the safety and effects of IL-1 blockade with anakinra on left ventricular (LV) remodeling after AMI. Ten patients with ST-segment elevation AMI were randomized to either anakinra 100 mg/day subcutaneously for 14 days or placebo in a double-blind fashion. Two cardiac magnetic resonance (CMR) imaging and echocardiographic studies were performed during a 10- to 14-week period. The primary end point was the difference in the interval change in the LV end-systolic volume index (LVESVi) between the 2 groups on CMR imaging. The secondary end points included differences in the interval changes in the LV end-diastolic volume index, and C-reactive protein levels. A +2.0 ml/m2 median increase (interquartile range +1.0, +11.5) in the LVESVi on CMR imaging was seen in the placebo group and a −3.2 ml/m2 median decrease (interquartile range −4.5, −1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m2 . On echocardiography, the median difference in the LVESVi change was 13.4 ml/m2 (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m2 , p = 0.033) and echocardiography (9.4 ml/m2 , p = 0.008). The change in C-reactive protein levels between admission and 72 hours after admission correlated with the change in the LVESVi (R = +0.71, p = 0.022). In conclusion, in the present pilot study of patients with ST-segment elevation AMI, IL-1 blockade with anakinra was safe and favorably affected by LV remodeling. If confirmed in larger trials, IL-1 blockade might represent a novel therapeutic strategy to prevent heart failure after AMI.</description><identifier>ISSN: 0002-9149</identifier><identifier>EISSN: 1879-1913</identifier><identifier>DOI: 10.1016/j.amjcard.2009.12.059</identifier><identifier>PMID: 20451681</identifier><identifier>CODEN: AJCDAG</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Biological and medical sciences ; Blood Chemical Analysis ; C-Reactive Protein - analysis ; Cardiology ; Cardiology. Vascular system ; Cardiovascular ; Coronary heart disease ; Cytokines ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Administration Schedule ; Echocardiography ; Female ; Follow-Up Studies ; Heart ; Heart attacks ; Heart failure ; Hospitals, University ; Humans ; Inflammation Mediators - analysis ; Injections, Subcutaneous ; Interleukin 1 Receptor Antagonist Protein - administration & dosage ; Interleukin-1 - analysis ; Magnetic Resonance Imaging ; Male ; Medical sciences ; Middle Aged ; Myocardial Infarction - complications ; Myocardial Infarction - diagnosis ; Myocarditis. Cardiomyopathies ; Pilot Projects ; Probability ; Reference Values ; Risk Assessment ; Treatment Outcome ; Ultrasonic imaging ; Ventricular Dysfunction, Left - prevention & control ; Ventricular Remodeling - drug effects ; Ventricular Remodeling - physiology ; Virginia</subject><ispartof>The American journal of cardiology, 2010-05, Vol.105 (10), p.1371-1377.e1</ispartof><rights>Elsevier Inc.</rights><rights>2010 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Sequoia S.A. May 15, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c555t-f54959151c7870760661d901d14137f7de3b0a1825c4a4ec1ea39fcfdc6a1c043</citedby><cites>FETCH-LOGICAL-c555t-f54959151c7870760661d901d14137f7de3b0a1825c4a4ec1ea39fcfdc6a1c043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002914910000664$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22804616$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20451681$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abbate, Antonio, MD, PhD</creatorcontrib><creatorcontrib>Kontos, Michael C., MD</creatorcontrib><creatorcontrib>Grizzard, John D., MD</creatorcontrib><creatorcontrib>Biondi-Zoccai, Giuseppe G.L., MD</creatorcontrib><creatorcontrib>Van Tassell, Benjamin W., PharmD</creatorcontrib><creatorcontrib>Robati, Roshanak, MD</creatorcontrib><creatorcontrib>Roach, Lenore M., RN</creatorcontrib><creatorcontrib>Arena, Ross A., PhD</creatorcontrib><creatorcontrib>Roberts, Charlotte S., ACNP</creatorcontrib><creatorcontrib>Varma, Amit, MD</creatorcontrib><creatorcontrib>Gelwix, Christopher C., MD</creatorcontrib><creatorcontrib>Salloum, Fadi N., PhD</creatorcontrib><creatorcontrib>Hastillo, Andrea, MD</creatorcontrib><creatorcontrib>Dinarello, Charles A., MD</creatorcontrib><creatorcontrib>Vetrovec, George W., MD</creatorcontrib><creatorcontrib>VCU-ART Investigators (see Appendix)</creatorcontrib><creatorcontrib>VCU-ART Investigators</creatorcontrib><title>Interleukin-1 Blockade With Anakinra to Prevent Adverse Cardiac Remodeling After Acute Myocardial Infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot Study)</title><title>The American journal of cardiology</title><addtitle>Am J Cardiol</addtitle><description>Acute myocardial infarction (AMI) initiates an intense inflammatory response in which interleukin-1 (IL-1) plays a central role. The IL-1 receptor antagonist is a naturally occurring antagonist, and anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot study was to test the safety and effects of IL-1 blockade with anakinra on left ventricular (LV) remodeling after AMI. Ten patients with ST-segment elevation AMI were randomized to either anakinra 100 mg/day subcutaneously for 14 days or placebo in a double-blind fashion. Two cardiac magnetic resonance (CMR) imaging and echocardiographic studies were performed during a 10- to 14-week period. The primary end point was the difference in the interval change in the LV end-systolic volume index (LVESVi) between the 2 groups on CMR imaging. The secondary end points included differences in the interval changes in the LV end-diastolic volume index, and C-reactive protein levels. A +2.0 ml/m2 median increase (interquartile range +1.0, +11.5) in the LVESVi on CMR imaging was seen in the placebo group and a −3.2 ml/m2 median decrease (interquartile range −4.5, −1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m2 . On echocardiography, the median difference in the LVESVi change was 13.4 ml/m2 (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m2 , p = 0.033) and echocardiography (9.4 ml/m2 , p = 0.008). The change in C-reactive protein levels between admission and 72 hours after admission correlated with the change in the LVESVi (R = +0.71, p = 0.022). In conclusion, in the present pilot study of patients with ST-segment elevation AMI, IL-1 blockade with anakinra was safe and favorably affected by LV remodeling. If confirmed in larger trials, IL-1 blockade might represent a novel therapeutic strategy to prevent heart failure after AMI.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blood Chemical Analysis</subject><subject>C-Reactive Protein - analysis</subject><subject>Cardiology</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular</subject><subject>Coronary heart disease</subject><subject>Cytokines</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Drug Administration Schedule</subject><subject>Echocardiography</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Heart</subject><subject>Heart attacks</subject><subject>Heart failure</subject><subject>Hospitals, University</subject><subject>Humans</subject><subject>Inflammation Mediators - analysis</subject><subject>Injections, Subcutaneous</subject><subject>Interleukin 1 Receptor Antagonist Protein - administration & dosage</subject><subject>Interleukin-1 - analysis</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Myocardial Infarction - complications</subject><subject>Myocardial Infarction - diagnosis</subject><subject>Myocarditis. Cardiomyopathies</subject><subject>Pilot Projects</subject><subject>Probability</subject><subject>Reference Values</subject><subject>Risk Assessment</subject><subject>Treatment Outcome</subject><subject>Ultrasonic imaging</subject><subject>Ventricular Dysfunction, Left - prevention & control</subject><subject>Ventricular Remodeling - drug effects</subject><subject>Ventricular Remodeling - physiology</subject><subject>Virginia</subject><issn>0002-9149</issn><issn>1879-1913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkl1v0zAUhiMEYmXwE0AWEgIuUnySOB83Q6Hio9IQ09aOC4Qszz4ZbhN72ElRfx1_DYeWDe1mV_7Qc95z7PeNoqdAp0Ahf7Oaim4lhVPThNJqCsmUsupeNIGyqGKoIL0fTSilSVxBVh1Ej7xfhSMAyx9GBwnNGOQlTKLfc9Oja3FYaxMDeddauRYKyVfd_yC1EeHaCdJbcuJwg6Yntdqg80hmobUWkpxiZxW22lySuglSpJZDj-Tz1sq_REvmphFO9toa8upcu0tttCAz23XW_ELRhj5Lo0dR3W9vWv6nu3CjzLfz2TKuTxffyYlubU_O-kFtXz-OHjSi9fhkvx5Gyw_vF7NP8fGXj_NZfRxLxlgfNyyrWAUMZFEWtMhpnoOqKCjIIC2aQmF6QQWUCZOZyFACirRqZKNkLkDSLD2MXu50r5z9OaDveae9xLYVBu3gecGyMi-rsribTNPgQsryQD6_Ra7s4Ex4Bk_KMErwNQ0Q20HSWe8dNvzK6U64LQfKxyTwFd8ngY9J4JDwkIRQ92wvPlx0qK6r_lkfgBd7QHgp2sYJI7W_4ZKSZjmMU77dcRi-d6PRcS81GolKO5Q9V1bfOcrRLQUZfNWh6Rq36K8fDdyHAn42xnZMLYRNMCpL_wCcV-nC</recordid><startdate>20100515</startdate><enddate>20100515</enddate><creator>Abbate, Antonio, MD, PhD</creator><creator>Kontos, Michael C., MD</creator><creator>Grizzard, John D., MD</creator><creator>Biondi-Zoccai, Giuseppe G.L., MD</creator><creator>Van Tassell, Benjamin W., PharmD</creator><creator>Robati, Roshanak, MD</creator><creator>Roach, Lenore M., RN</creator><creator>Arena, Ross A., PhD</creator><creator>Roberts, Charlotte S., ACNP</creator><creator>Varma, Amit, MD</creator><creator>Gelwix, Christopher C., MD</creator><creator>Salloum, Fadi N., PhD</creator><creator>Hastillo, Andrea, MD</creator><creator>Dinarello, Charles A., MD</creator><creator>Vetrovec, George W., MD</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TS</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7Z</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20100515</creationdate><title>Interleukin-1 Blockade With Anakinra to Prevent Adverse Cardiac Remodeling After Acute Myocardial Infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot Study)</title><author>Abbate, Antonio, MD, PhD ; Kontos, Michael C., MD ; Grizzard, John D., MD ; Biondi-Zoccai, Giuseppe G.L., MD ; Van Tassell, Benjamin W., PharmD ; Robati, Roshanak, MD ; Roach, Lenore M., RN ; Arena, Ross A., PhD ; Roberts, Charlotte S., ACNP ; Varma, Amit, MD ; Gelwix, Christopher C., MD ; Salloum, Fadi N., PhD ; Hastillo, Andrea, MD ; Dinarello, Charles A., MD ; Vetrovec, George W., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c555t-f54959151c7870760661d901d14137f7de3b0a1825c4a4ec1ea39fcfdc6a1c043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Blood Chemical Analysis</topic><topic>C-Reactive Protein - analysis</topic><topic>Cardiology</topic><topic>Cardiology. 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The IL-1 receptor antagonist is a naturally occurring antagonist, and anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot study was to test the safety and effects of IL-1 blockade with anakinra on left ventricular (LV) remodeling after AMI. Ten patients with ST-segment elevation AMI were randomized to either anakinra 100 mg/day subcutaneously for 14 days or placebo in a double-blind fashion. Two cardiac magnetic resonance (CMR) imaging and echocardiographic studies were performed during a 10- to 14-week period. The primary end point was the difference in the interval change in the LV end-systolic volume index (LVESVi) between the 2 groups on CMR imaging. The secondary end points included differences in the interval changes in the LV end-diastolic volume index, and C-reactive protein levels. A +2.0 ml/m2 median increase (interquartile range +1.0, +11.5) in the LVESVi on CMR imaging was seen in the placebo group and a −3.2 ml/m2 median decrease (interquartile range −4.5, −1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m2 . On echocardiography, the median difference in the LVESVi change was 13.4 ml/m2 (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m2 , p = 0.033) and echocardiography (9.4 ml/m2 , p = 0.008). The change in C-reactive protein levels between admission and 72 hours after admission correlated with the change in the LVESVi (R = +0.71, p = 0.022). In conclusion, in the present pilot study of patients with ST-segment elevation AMI, IL-1 blockade with anakinra was safe and favorably affected by LV remodeling. If confirmed in larger trials, IL-1 blockade might represent a novel therapeutic strategy to prevent heart failure after AMI.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>20451681</pmid><doi>10.1016/j.amjcard.2009.12.059</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The American journal of cardiology, 2010-05, Vol.105 (10), p.1371-1377.e1 |
| issn | 0002-9149 1879-1913 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Biological and medical sciences Blood Chemical Analysis C-Reactive Protein - analysis Cardiology Cardiology. Vascular system Cardiovascular Coronary heart disease Cytokines Dose-Response Relationship, Drug Double-Blind Method Drug Administration Schedule Echocardiography Female Follow-Up Studies Heart Heart attacks Heart failure Hospitals, University Humans Inflammation Mediators - analysis Injections, Subcutaneous Interleukin 1 Receptor Antagonist Protein - administration & dosage Interleukin-1 - analysis Magnetic Resonance Imaging Male Medical sciences Middle Aged Myocardial Infarction - complications Myocardial Infarction - diagnosis Myocarditis. Cardiomyopathies Pilot Projects Probability Reference Values Risk Assessment Treatment Outcome Ultrasonic imaging Ventricular Dysfunction, Left - prevention & control Ventricular Remodeling - drug effects Ventricular Remodeling - physiology Virginia |
| title | Interleukin-1 Blockade With Anakinra to Prevent Adverse Cardiac Remodeling After Acute Myocardial Infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot Study) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T21%3A08%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Interleukin-1%20Blockade%20With%20Anakinra%20to%20Prevent%20Adverse%20Cardiac%20Remodeling%20After%20Acute%20Myocardial%20Infarction%20(Virginia%20Commonwealth%20University%20Anakinra%20Remodeling%20Trial%20%5BVCU-ART%5D%20Pilot%20Study)&rft.jtitle=The%20American%20journal%20of%20cardiology&rft.au=Abbate,%20Antonio,%20MD,%20PhD&rft.aucorp=VCU-ART%20Investigators%20(see%20Appendix)&rft.date=2010-05-15&rft.volume=105&rft.issue=10&rft.spage=1371&rft.epage=1377.e1&rft.pages=1371-1377.e1&rft.issn=0002-9149&rft.eissn=1879-1913&rft.coden=AJCDAG&rft_id=info:doi/10.1016/j.amjcard.2009.12.059&rft_dat=%3Cproquest_cross%3E2035765581%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=288250093&rft_id=info:pmid/20451681&rft_els_id=1_s2_0_S0002914910000664&rfr_iscdi=true |