What is the clinical evidence from this study?

Study design: RCT. Population: ST-segment elevation myocardial infarction (n=99). Intervention: Anakinra vs. Placebo. Primary outcome: Change in total white blood cell count (RR 0.65, 95% CI 0.52-0.81, p=0.008).

January 24, 2022Open Access

Effect of interleukin-1 blockade with anakinra on leukocyte count in patients with ST-segment elevation acute myocardial infarction

Q: What does this research mean for the field?

Anakinra treatment results in a 35% reduction in total WBC count in patients with ST-segment elevation myocardial infarction compared to a 21% reduction in the placebo group at 72 hours after treatment initiation. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

MBMarco Giuseppe Del BuonoHeart Failure & Transplant JDJuan Ignacio DamonteHospital Universitario Austral CTCory R. TrankleHeart Failure & Transplant

Key Result

Anakinra treatment resulted in a 35% reduction in total WBC count compared to a 21% reduction in the placebo group at 72 hours after treatment initiation.

Study Design

Type

RCT (n=99)

Blinding

Double-blind

Multicenter

Yes

Structured PICO

Does anakinra reduce leukocyte count in patients with ST-segment elevation acute myocardial infarction?

Population

99 patients with ST-segment elevation acute myocardial infarction (STEMI), median age 55, 81% male. Key exclusions: contraindications to anakinra, chronic inflammatory or infectious disease, or preexisting structural or functional severe cardiac abnormalities.

Intervention

Anakinra (recombinant human interleukin-1 [IL-1] receptor antagonist) 100 mg once daily alternating with placebo every 12 h, or 100 mg twice daily every 12 h, for 14 days (both anakinra arms pooled for analysis). First dose administered within 12 h of coronary angiography.

Comparator

Matching placebo twice daily every 12 h for 14 days.

Outcome

Change in total white blood cell (WBC) count and differential count (absolute neutrophil count, absolute eosinophil count) at 72 hours, 14 days, and 3 months.surrogate

In patients with STEMI, IL-1 blockade with anakinra accelerates the resolution of leukocytosis and neutrophilia, providing a potential mechanistic explanation for its clinical benefits in reducing heart failure events.

Main Result

Effect estimate: RR 0.65 (95% CI 0.52-0.81)

Absolute Event Rate: 7.5% vs 8.3%

p-value: p=0.008

Limitations

Small sample size of 99 patients
Post-hoc analysis of results
Lack of measurement of WBC count at earlier time points

Abstract

Abstract Leukocytosis is a common finding in patients with ST elevation myocardial infarction (STEMI) and portends a poor prognosis. Interleukin 1-β regulates leukopoiesis and pre-clinical studies suggest that anakinra (recombinant human interleukin-1 IL-1 receptor antagonist) suppresses leukocytosis in myocardial infarction. However, the effect of IL-1 blockade with anakinra on leukocyte count in patients with STEMI is unknown. We reviewed the white blood cell (WBC) and differential count of 99 patients enrolled in a clinical trial of anakinra (n = 64) versus placebo (n = 35) for 14 days after STEMI. A complete blood cell count with differential count were obtained at admission, and after 72 h, 14 days and 3 months. After 72 h from treatment, anakinra compared to placebo led to a statistically significant greater percent reduction in total WBC count (− 35% − 48 to − 24 vs. − 21% − 34 to − 10, P = 0.008), absolute neutrophil count (− 48% − 60 to − 22 vs. − 27% − 46 to − 5, P = 0.004) and to an increase in absolute eosinophil count (+ 50% 0 to + 100 vs. 0% − 50 to + 62, P = 0.022). These changes persisted while on treatment at 14 days and were no longer apparent at 3 months after treatment discontinuation. We found that in patients with STEMI IL-1 blockade with anakinra accelerates resolution of leukocytosis and neutrophilia. This modulation may represent one of the mechanisms by which IL-1 blockade improves clinical outcomes.

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