Significant Stagnancy in the Search and Use of New Antiarrhythmic Agents With Some Recent Beams of Hope

Over the last few decades, there has been noteworthy long-lasting stagnancy in the field of antiarrhythmic drugs (AAD), with the development of novel AAD notably declining over the years. Although ablation therapy has dominated, there remains an unmet need for effective and safe antiarrhythmic therapy in those choosing a conservative approach and those failing the ablation procedure( s). Also, in patients with life-threatening ventricular arrhythmias, in the era of the implantable cardioverter defibrillator dominance, many patients require effective and safe AAD therapy to mitigate the recurrence of arrhythmias and the delivery of painful and unpleasant device shocks. The repurposing and reformulation of current drugs in circulation for novel therapeutic uses may provide new avenues for developing antiarrhythmic treatments that can assist in curtailing cardiac arrhythmia- associated morbidity and mortality, and ameliorate the quality of life for millions of patients. Stressful factors may lead to endothelial dysfunction and a surge in blood pressure, contributing to the emergence of cardiac arrhythmogenic effects, including myocardial fibrosis and remodeling of structural, ion channels, and connexin 43 channels, with consequent dysfunction. Agents influencing this latter protein may have cardioprotective and potentially antiarrhythmic effects. In this review of new antiarrhythmic agents, the advantages of sodium-glucose co-transporter inhibitors, and also those of pirfenidone, ranolazine, sotatercept, mirabegron, nintedanib, and melatonin are discussed. Some of these agents have been approved for other indications and repurposed for use in managing arrhythmias. Finding novel antiarrhythmic therapeutic approaches may be challenging for further research.