Investigational antiarrhythmic agents: promising drugs in early clinical development

Jordi Heijman, Shokoufeh Ghezelbash, Dobromir Dobrev*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

21 Citations (Web of Science)

Abstract

Introduction: Although there have been important technological advances for the treatment of cardiac arrhythmias (e.g., catheter ablation technology), antiarrhythmic drugs (AADs) remain the cornerstone therapy for the majority of patients with arrhythmias. Most of the currently available AADs were coincidental findings and did not result from a systematic development process based on known arrhythmogenic mechanisms and specific targets. During the last 20 years, our understanding of cardiac electrophysiology and fundamental arrhythmia mechanisms has increased significantly, resulting in the identification of new potential targets for mechanism-based antiarrhythmic therapy.Areas covered: Here, we review the state-of-the-art in arrhythmogenic mechanisms and AAD therapy. Thereafter, we focus on a number of antiarrhythmic targets that have received significant attention recently: atrial-specific K+-channels, the late Na+-current, the cardiac ryanodine-receptor channel type-2, and the small-conductance Ca2+-activated K+-channel. We highlight for each of these targets available antiarrhythmic agents and the evidence for their antiarrhythmic effect in animal models and early clinical development.Expert opinion: Targeting AADs to specific subgroups of well-phenotyped patients is likely necessary to detect improved outcomes that may be obscured in the population at large. In addition, specific combinations of selective AADs may have synergistic effects and may enable a mechanism-based tailored antiarrhythmic therapy.

Original languageEnglish
Pages (from-to)897-907
Number of pages11
JournalExpert Opinion on Investigational Drugs
Volume26
Issue number8
DOIs
Publication statusPublished - 2017

Keywords

  • Antiarrhythmic drugs
  • atrial fibrillation
  • calcium handling
  • ion channels
  • sudden cardiac death
  • POLYMORPHIC VENTRICULAR-TACHYCARDIA
  • LATE SODIUM CURRENT
  • CHRONIC ATRIAL-FIBRILLATION
  • SMALL-CONDUCTANCE CALCIUM
  • SUDDEN CARDIAC DEATH
  • QUESTIONING FLECAINIDES MECHANISM
  • ACTIVATED POTASSIUM CHANNELS
  • RECEPTOR POTENTIAL CHANNELS
  • INTACT PORCINE MODEL
  • HEART-FAILURE

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