Cardiovascular Risk Modulation and Inflammatory Biomarker Dynamics of Selective Interleukin-1-Beta Inhibition in Resistant Atherosclerotic Disease

International Journal of Cardiology | Vol. 17, No. 8, August 2026 | pp. 41–48

DOI: 10.46882/2026/IJC/001918

Original Research Article

Cardiovascular Risk Modulation and Inflammatory Biomarker Dynamics of Selective Interleukin-1-Beta Inhibition in Resistant Atherosclerotic Disease

Carlos Mendez¹, Sofia Rodriguez¹

¹ Instituto del Corazón, Hospital Clínico San Carlos, Madrid, Spain

Abstract:
Residual inflammatory risk persists as a major cause of recurrent ischemic events in patients with established coronary artery disease despite aggressive lipid-lowering therapy. This prospective, double-blind trial investigated the impact of a novel, highly selective monoclonal antibody targeting interleukin-1-beta (IL-1β), Glembatumumab, on major adverse cardiovascular events (MACE) and vascular inflammation markers. We randomized 340 patients with stable coronary artery disease and a persistent high-sensitivity C-reactive protein (hs-CRP) level greater than or equal to 3.0 mg/L to receive subcutaneous Glembatumumab (100 mg every 4 weeks) or a placebo. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, or urgent revascularization. At 18 months, the incidence of the primary composite endpoint was significantly lower in the active treatment arm compared to the placebo arm (8.8% vs. 15.3%, Hazard Ratio = 0.55, 95% Confidence Interval: 0.34-0.89, p = 0.014). This clinical improvement occurred independently of low-density lipoprotein cholesterol levels, which remained unchanged in both groups. Glembatumumab therapy induced a rapid and sustained reduction in circulating hs-CRP levels by 52.4% (p < 0.001) and interleukin-6 levels by 46.1% (p < 0.001) relative to baseline. Rates of serious neutropenia or opportunistic infections did not differ significantly between the groups. Target-specific inhibition of IL-1β with Glembatumumab significantly reduces residual ischemic risk and suppresses systemic inflammatory cascades in patients with advanced atherosclerotic disease.

Keywords: Atherosclerosis, Inflammation, Interleukin-1-beta, Monoclonal antibodies, C-reactive protein, Major adverse cardiovascular events

Received: May 20, 2026; Revised: June 25, 2026; Accepted: July 10, 2026; Published: August 14, 2026

Citation: Mendez C, Rodriguez S. Cardiovascular Risk Modulation and Inflammatory Biomarker Dynamics of Selective Interleukin-1-Beta Inhibition in Resistant Atherosclerotic Disease. International Journal of Cardiology, 2026; 17(8): 41–48. DOI: 10.46882/2026/IJC/001918

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