Primary percutaneous coronary intervention (PCI) is the reference treatment for myocardial infarction, but its effectiveness decreases with time to catheterisation. Early administration of antiplatelet agents can inhibit thrombus progression and facilitate reperfusion, but randomized trials with P2Y12 inhibitors have not shown a reperfusion benefit, noted Arnoud van’t Hof from Maastricht University Medical Center (Netherlands) and colleagues.
GpIIb/IIIa inhibitors are more potent antiplatelet agents and have been associated with improved patency of the infarct-related artery and better ventricular function when administered early. However, first-generation agents in this class have significant limitations, including the need for continuous infusion and an increased risk of severe bleeding and thrombocytopenia, the authors add.
Zalunfiban was specifically designed for use by first responders and emergency services, to be administered as a single subcutaneous injection, with maximal effect reached within 15 minutes and disappearing after two hours, Celecor stated.
The international, randomized, double-blind Phase III CELEBRATE trial, presented in the Late-Breaking Science session, included 2,467 patients with suspected STEMI, seen within four hours of symptom onset at home, in the ambulance, or in hospital emergency departments. They received, as quickly as possible at first medical contact before hospitalization, zalunfiban at 0.11 mg/kg or 0.13 mg/kg, or placebo.
The primary efficacy endpoint included seven hierarchical events, ranked from most to least severe, within 30 days following revascularization: all-cause death, stroke, recurrent myocardial infarction, acute stent thrombosis, new-onset heart failure or rehospitalization for heart failure, infarct size more than 30 times the upper limit of normal 24 hours after PCI, and absence of these events.
Zalunfiban was associated with a statistically significant reduction in the risk of experiencing primary endpoint events, with an odds ratio (OR) of 0.79, according to results also published in NEJM Evidence.
Analysis of individual primary endpoint events showed a death rate of 2.3% with zalunfiban versus 2.2% with placebo, a stroke rate of 0.7% versus 0.8%, a recurrent myocardial infarction rate of 1.9% versus 1.2% (not significant), an acute stent thrombosis rate within 24 hours post-PCI of 0.2% versus 1.0% (relative risk reduced by 82% with zalunfiban), a new-onset heart failure or rehospitalization rate of 6.5% versus 8.1%, and increased infarct size in 85.4% versus 88.5% of patients.
None of these events occurred in 13.3% of patients treated with zalunfiban versus 9.8% with placebo, corresponding to a significantly increased relative likelihood (OR) of 41% to avoid one or more of these events in the zalunfiban group. The authors calculated that 29 patients need to be treated to prevent the occurrence of one or more of these events.
The rate of severe or potentially fatal bleeding, which constituted the primary safety endpoint, was similar in both groups (1.2% versus 0.8%). However, there were significantly more mild-to-moderate bleeding events in the zalunfiban group (6.4% versus 2.5%).
Reperfusion assessed by angiography was significantly faster with zalunfiban.
“The CELEBRATE data show that we have the potential to transform the way we treat STEMI,” commented Prof. van’t Hof, cited in the Celecor statement.
“These data demonstrate the efficacy and safety profile of early subcutaneous platelet inhibition as an adjunct to standard reperfusion therapy in STEMI,” the authors of the NEJM Evidence article concluded.
Celecor plans to submit a marketing authorization application to the U.S. Food and Drug Administration (FDA) in early 2026.
(NEJM Evidence)
Source:
