Unmet Medical Need Peter R. Kowey, MD

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Unmet Medical NeedPeter R. Kowey, MD

• President, Main Line Health Heart Center
• William Wikoff Smith Chair in Cardiovascular
  Research
• Professor of Medicine and Clinical Pharmacology
• Jefferson Medical College of Thomas Jefferson
  University

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Epidemiology Scope of the Problem

• More than 2 million patients in the US
• Major impact on the elderly
• Prevalence increasing as population ages
• Significant economic impact
• Substantial morbidity due to symptoms
• Associated with stroke, heart failure, and death
• Most common arrhythmia requiring hospitalization

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Gender Considerations in AFib/AFl

• Womens longer lives place them at increased risk
• Women tend to have worse cardiac outcomes
• Well-documented gender differences in QT effects
  and incidence of TdP
• Women under-represented in relevant clinical
  trials

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Rate vs Rhythm Control Trials

• Applicable to subsets of patients with AF
• Over-extrapolated to younger and symptomatic
  patients
• Encourages under-treatment of patients with
  severe symptoms and poor life quality

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Issues in Adoption of Rate-Control Strategy

• Residual symptoms
• Age-dependence
• Duration of disease
• Inadequate chronotropic control
• May mandate pacing
• Need for anticoagulation for acute conversion
  after 48 hrs

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Issues in Current Antiarrhythmic Therapy

• Inadequate efficacy with frequent recurrence
• PVI/atrial ablation not applicable to a large
  segment of patients
• Safety concerns with drugs and ablation
• Does not obviate repeated cardioversions or
  anticoagulation

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Sinus Rhythm Restoration Has a Premium

• Symptom relief
• Prevention of electrical/mechanical remodeling
• Potential avoidance of anticoagulation
• Reduced cost of care by preventinghospitalization
  
• Complementary treatment approaches

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Restoration of Sinus Rhythm

• Electrical conversion
• Convenience/logistics
• Expense
• Poor patient acceptance
• Early recurrence
• Complicated by tachy- and bradyarrhythmias, skin
  burns, hypotension, device malfunction

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Restoration of Sinus Rhythm

• Pharmacologic therapy
• Modest success
• Obviates anesthesia/fasting
• Drug specific toxicity
• AF duration-dependent
• IRAF/ERAF less frequent
• Consider prior antiarrhythmic drug treatment

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Unmet Medical Need for a Drug with

• Defined efficacy/safety profile for men and women
• Defined dosing/instructions for use
• Simple kinetics (renal impairment/metabolism)
• Durability of effect
• Utility in AF of longer duration
• Efficacy/safety in patients with structural
  heart disease