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Atrial Fibrillation: Emerging Drug Discovery Targets and Therapeutic Candidates

  • ID: 338102
  • Report
  • May 2006
  • 69 Pages
  • Lead Discovery
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The commonly quoted figure describing the number of Americans with atrial fibrillation is about 2.2 million. The current prevalence is now considerably larger than this and is set to continue growing. The condition is a risk factor for stroke and patients with atrial fibrillation tend to suffer more severely from strokes than the general population.

Treatment options are currently sub-optimal largely depending on the use of rate controlling agents and anticoagulants. The use of rate control agents rather than antiarrhythmics stems from 5 major clinical trials demonstrating that rate control is as effective as rhythm control an associated with fewer adverse effect. This however is largely a reflection of the need to develop next generation antiarrhythmics.

The global antiarrhythmic market is set to enter a period of revival reaching $3.5 billion by 2015. This resurgence is being led by Cardiome's RSD1235 which is expected to enter the market imminently and predicted to command 27% of the whole market by 2015. The blockbuster potential of RSD1235 and the relatively empty late stage pipeline for antiarrhythmic should represent a powerful driver for companies in the cardiovascular or ion channel arena to develop new candidates.

Atrial Fibrillation: Emerging drug discovery targets and therapeutic candidates is a state of the art report produced for all in the drug development sector. The report offers a detailed look at the biology of cardiac rhythm; the etiology and current treatment of arrhythmias and a proof of concept study to identify molecular targets for next generation antiarrhythmics. The report fully evaluates pipeline candidates for the treatment of atrial fibrillation and discusses future pharmacological approaches in the context of interventional strategies such as catheter ablation and surgical approaches.

The report also provides a detailed look at the related condition: ventricular fibrillation.
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Normal cardiac rhythms: An introduction to the electrophysiology and molecular biology of the sinus rhythm

The electrophysiology of the sinus rhythm
Phases of the action potential
Channels governing the cardiac action potential and their molecular correlates
NAV channels
CAV channels
Voltage gated potassium channels
Transient Outward Kv Currents
Delayed Rectifier Kv Currents
Inwardly rectifying K+ (Kir) currents
Cardiac arrhythmias

Description of major arrhythmias
Atrial fibrillation

Incidence & General Introduction
Signs, symptoms & outcomes
Subtypes of AF
Pathophysiological mechanisms of atrial fibrillation
Focal activation
Electrical pathways underlying atrial fibrillation
Molecular mechanisms underlying atrial fibrillation
Electrophysiological remodeling
Gap junctions
Altered neural input
Defects in AV conduction
Structural abnormalities
The renin-angiotensin system
Current treatment of atrial fibrillation
Pharmacological approaches to atrial fibrillation
Rate control treatment
Specific agents
Nondihydropyridine Calcium Channel Blockers
Rhythm control treatment
Specific agents
Class IA antiarrhythmics
Class IC antiarrhythmics
Class III antiarrhythmics
Use of cardioversion strategies
Approaches to the maintenance of sinus rhythm
Guidelines on the selection of antiarrhythmic therapeutics
Rate or rhythm-The trials
Limitations of the 5 main trials comparing rate and rhythm control
Current guidelines for the overall pharmacological treatment of atrial fibrillation
Newly Discovered Atrial Fibrillation
Recurrent Paroxysmal Atrial Fibrillation
Recurrent Persistent Atrial Fibrillation
Permanent Atrial Fibrillation
Anticoagulants and their role in the treatment of atrial fibrillation
Interventional approaches to atrial fibrillation
Catheter ablation of the pulmonary vein
Ablation of the AV node
Electrical Cardioversion
Surgical treatment
The Maze procedure
The mini-Maze
Radiofrequency Ablation
Microwave Technology
Removal of the left atrial appendage
Medical Devices
Comparative analysis of treatments for atrial fibrillation
Ablation or Minimaze
Future requirements for the treatment of atrial fibrillation
Ventricular fibrillation

Causes of ventricular fibrillation
Implantable cardioverter defibrillators as an approach to reducing mortality through ventricular fibrillation
The MADIT trials
Mechanism of ventricular fibrillation
Dispersion of refractoriness
APD restitution
Antiarrhythmics for the reversal and prevention of ventricular fibrillation
Amiodarone and other antiarrhythmics in ventricular fibrillation
Molecular targets for the prevention of ventricular fibrillation
Calcium Channels
Potassium IKr and IKs Currents
Potential targets for resuscitation following ventricular fibrillation
KATP channels
Gap Junction activators
The Na+/Ca2+-exchanger
Ablative surgery as an approach to ventricular fibrillation
Profiles of products in clinical stage development for the treatment of atrial & ventricular fibrillation

Multi-Channel Blockers
Dronedarone (SR 33589b)
Tedisamil (Pulzium)
Channel Blockers with atrial selectivity
A1-adenosine receptor agonist
Tecadenoson (CVT-510)
Candidates for the treatment of ventricular fibrillation
The Market for Antiarrhythmic agents

Conclusions & Recommendations
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