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 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/m(2) 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/m(2) median decrease (interquartile range -4.5, -1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m(2). On echocardiography, the median difference in the LVESVi change was 13.4 ml/m(2) (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m(2), p = 0.033) and echocardiography (9.4 ml/m(2), 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.
Abbate
Antonio
A
Virginia Commonwealth University, VCU Pauley Heart Center, Richmond, Virginia, USA. abbatea@yahoo.com
Kontos
Michael C
MC
Grizzard
John D
JD
Biondi-Zoccai
Giuseppe G L
GG
Van Tassell
Benjamin W
BW
Robati
Roshanak
R
Roach
Lenore M
LM
Arena
Ross A
RA
Roberts
Charlotte S
CS
Varma
Amit
A
Gelwix
Christopher C
CC
Salloum
Fadi N
FN
Hastillo
Andrea
A
Dinarello
Charles A
CA
Vetrovec
George W
GW
D000328:Adult; D001774:Blood Chemical Analysis; D002097:C-Reactive Protein / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006785:Hospitals, University; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D007279:Injections, Subcutaneous; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage*; D007375:Interleukin-1 / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications* / Q000175:diagnosis; D010865:Pilot Projects; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control*; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology; D014768:Virginia
D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D002097:C-Reactive Protein