Memantine for Premature Atrial Contractions
A Phase 2 Randomized Clinical Trial
In this phase 2 double-blind randomized trial, memantine — an NMDA-receptor antagonist — suppressed premature atrial contractions in symptomatic adults with ≥1,000 PACs per 24 h. The result opens a genuinely new pharmacological route for atrial arrhythmia, grounded in the recently identified cardiac glutamatergic system. If PAC reduction translates into downstream AF and stroke benefit, it could reshape atrial arrhythmia treatment.
Summary
BACKGROUND:Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias.METHODS:We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (≥50% PAC reduction), perce
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