Attenuation of systemic inflammatory response in acute decompensated HF
Interleukin-1 blockade in acute decompensated heart failure: A randomized, double-blinded, placebo-controlled pilot study.Van Tassell BW, Abouzaki NA, Erdle CO, et al.
Journal of Cardiovascular Pharmacology 2016; published online ahead of print
The rates of acute decompensated heart failure (ADHF) requiring hospitalisation have tripled over the past 25 years, and ADHF leads to [1-3]:
- mortality of 3-4% during admission
- rehospitalisation of 50%
- increased HF morbidity and mortality after discharge
In this randomised, double-blinded, placebo-controlled study, it was investigated whether IL-1 blockage with anakinra can attenuate the acute inflammatory response in patients with ADHF. Interleukin-1 (IL-1) is an inflammatory cytokine that is markedly elevated during ADHF as measured by the surrogate biomarkers C-reactive protein and IL-6, and is sufficient to cause cardiac dysfunction in cellular and animal models of HF [6,7].
30 patients with ADHF, reduced left ventricular ejection fraction (LVEF<40%), and elevated C reactive protein (CRP) levels (≥5 mg/L) were randomized to either anakinra 100 mg twice daily for 3 days followed by once daily for 11 days or matching placebo, in a 1:1 double blinded fashion. Daily CRP plasma levels were measured using a high-sensitivity assay during hospitalization and then again at 14 days and the area-under-the-curve (AUC) and interval changes (delta) were evaluated.
Fourteen patients in the anakinra group (93%) and 13 patients in the placebo group (87%) completed the study protocol through the first 72 hours (or discharge) and were converted to once-daily dosing.
A total of 9 patients in the anakinra group (60%) and 8 patients in the placebo group (53%) returned to clinic for the 14-day clinical follow-up.
- CRP values during the first 72 hours of treatment vs baseline:
- patients randomised to placebo: -6.0%; 95% CI: -32.6% to 54.5%; P=0.88
- Patients on anakinra were more likely to achieve a 50% reduction in CRP within 72 hours: 75% vs 17%, P=0.008
- CRP values after 14 days of treatment vs baseline:
- patients randomised to placebo: -85%; 95% CI: -92% to -56%; P<0.01
- Patients receiving anakinra were more likely to achieve a “normalized” CRP value (<2 mg/L) at 14 days (78% vs 25%, P=0.040)
- Treatment with anakinra produced significant reductions in IL-6:
- after 14 days: 0.44; 95% CI: 0.30 - 0.90; P<0.05
- Treatment with anakinra was well tolerated
ConclusionIn patients with ADHF, 14 days of IL-1 blockade with anakinra reduced the systemic inflammatory response, and was well tolerated. These results provide confirmatory evidence that IL-1 drives the systemic inflammatory response during ADHF, and mediates the IL-6 and CRP response in this setting.
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