A first pilot study of interleukin-1 blockade in ST-segment elevation acute myocardial
infarction showed improved remodeling. In the present second pilot study, we enrolled
30 patients with clinically stable ST-segment elevation acute myocardial infarction
randomized to anakinra, recombinant interleukin-1 receptor antagonist, 100 mg/day
for 14 days or placebo in a double-blind fashion. The primary end point was the difference
in the interval change in left ventricular (LV) end-systolic volume index between
the 2 groups within 10 to 14 weeks. The secondary end points included changes in the
LV end-diastolic volume index, LV ejection fraction, and C-reactive protein levels.
No significant changes in end-systolic volume index, LV end-diastolic volume index,
or LV ejection fraction were seen in the placebo group. Compared to placebo, treatment
with anakinra led to no measurable differences in these parameters. Anakinra significantly
blunted the increase in C-reactive protein between admission and 72 hours (+0.8 mg/dl,
interquartile range −6.4 to +4.2, vs +21.1 mg/dl, interquartile range +8.7 to +36.6,
p = 0.002), which correlated with the changes in LV end-diastolic volume index and
LV end-systolic volume index at 10 to 14 weeks (R = +0.83, p = 0.002, and R = +0.55,
p = 0.077, respectively). One patient in the placebo group (7%) died. One patient
(7%) in the anakinra group developed recurrent acute myocardial infarction. More patients
were diagnosed with new-onset heart failure in the placebo group (4, 27%) than in
the anakinra group (1, 7%; p = 0.13). When the data were pooled with those from the
first Virginia Commonwealth University-Anakinra Remodeling Trial (n = 40), this difference
reached statistical significance (30% vs 5%, p = 0.035). In conclusion, interleukin-1
blockade with anakinra blunted the acute inflammatory response associated with ST-segment
elevation acute myocardial infarction. Although it failed to show a statistically
significant effect on LV end-systolic volume index, LV end-diastolic volume index,
or LV ejection fraction in this cohort of clinically stable patients with near-normal
LV dimensions and function, anakinra led to a numerically lower incidence of heart
failure.
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Article info
Publication history
Published online: March 01, 2013
Accepted:
January 21,
2013
Received in revised form:
January 21,
2013
Received:
December 3,
2012
Footnotes
This study was funded by Scientist Development grant 10SDG 3030051 from the American Heart Association (Dallas, Texas), a Presidential Research Incentive Program of the Virginia Commonwealth University to Dr. Abbate, and by the internal funds of the VCU Pauley Heart Center and Victoria Johnson Research Laboratories; Dr. Van Tassell was supported by institutional K12 award KL2RR031989 from the National Institutes of Health (Bethesda, Maryland); and Dr. Dinarello was supported by grant AI-15614 from the National Institutes of Health (Bethesda, Maryland).
A complete list of the investigators can found in the On-Line Appendix.
See page 1400 for disclosure information.
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© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
