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Athena trial

Athena trial

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Athena Athena Presentation Transcript

  • ATHENA Trial (A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter) Presented at Heart Rhythm 2008 in San Francisco, USA Presented by Stefan H. Hohnloser, MD ATHENA Trial Copyleft Clinical Trial Results. You Must Redistribute Slides
  • ATHENA Trial: Background
    • Atrial fibrillation (AF) impairs patients’ lives, leading to increased risks of cardiovascular complications.
    • Over the course of 20 years of clinical drug trials in AF no drug has demonstrated a significant reduction in the risk of cardiac death.
    • ATHENA set out to evaluate the effect of Multaq ® (dronedarone), a multi-channel blocker with anti-adrenergic properties, on a composite primary endpoint of all-cause mortality and cardiovascular hospitalization in patients with AF.
    JCE 2008; 19.1/Heart Rhythm 2008
    • Dronedarone (Multaq®) manufactured by Sanofi-aventis is a new multi-channel blocker that affects the calcium, potassium and sodium channels and has anti-adrenergic properties.
    • Unlike amiodarone, this drug does not contain iodine radical and hence does not result in adverse effects on thyroid and lung functions.
    ATHENA Trial: Dronedarone JCE 2008; 19.1/Heart Rhythm 2008 View slide
  • ATHENA Trial: Study Design
      • Primary Endpoint: composite of all-cause mortality combined with cardiovascular hospitalization
      • Secondary Endpoint: death from any cause, cardiovascular death, hospitalization for cardiovascular reasons
    Multaq ® (dronedarone) 400 mg BID Placebo 4,628 patients > 75 years with atrial fibrillation or 70-75 years with atrial fibrillation and at least one additional cardiovascular risk factor prior to randomization. Double blind. Randomized. Placebo controlled. International multicenter. Mean follow-up 21 months. JCE 2008; 19.1/Heart Rhythm 2008 R 12-30 mos. follow-up Copyleft Clinical Trial Results. You Must Redistribute Slides View slide
  • ATHENA Trial: Inclusion Criteria
    • ≥ 75 yrs with or without additional risk factors
    • ≥ 70 yrs with at least one of the following risk factors: arterial hypertension (ongoing therapy with at least two antihypertensive drugs of different classes), diabetes mellitus, prior stroke or transient ischemic attack or systemic embolism, left atrium diameter ≥ 50 mm by M-mode echocardiography, LVEF < 0.40 by 2D-echocardiography.
    JCE 2008; 19.1/Heart Rhythm 2008 Copyleft Clinical Trial Results. You Must Redistribute Slides
  • ATHENA Trial: Inclusion Criteria Cont.
    • Availability of one 12-lead ECG within the last 6 months, indicating prior or current AF/A flutter
    • Access to a second 12-lead ECG within the last 6 months showing prior or current SR
    JCE 2008; 19.1/Heart Rhythm 2008 Copyleft Clinical Trial Results. You Must Redistribute Slides
  • ATHENA Trial: Exclusion Criteria
    • Presence of one of the following cardiac conditions:
    • Permanent AF
    • Unstable hemodynamic situation (i.e., recently decompensated heart failure)
    • Congestive heart failure NYHA class IV
    • Planned major non-cardiac or cardiac surgery
    • Acute myocarditis
    • Bradycardia < 50 bpm and/or a PR interval > 0.28 seconds
    • Significant sinus node disease in the past, if not treated with a pacemaker
    Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm 2008
  • ATHENA Trial: Exclusion Criteria cont.
    • Refusal or inability to give informed consent
    • Any non-cardiac severe illness limiting life expectancy
    • Pregnancy and breast feeding
    • Women of child-bearing potential without adequate birth control
    • Participation in another clinical trial
    Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm 2008
  • ATHENA Trial: Exclusion Criteria cont.
    • A calculated GFR at baseline < 10mL/min using the Cockroft Gault formula
    • Potassium level < 3.5 mmol/L if not corrected
    • Need for concomitant medication prohibited within ATHENA (i.e., other antiarrhythmic drugs of Vaughan-Williams class I or III)
    Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm 2008
  • ATHENA Trial: Baseline Characteristics JCE 2008; 19.1 /Heart Rhythm 2008 Copyleft Clinical Trial Results. You Must Redistribute Slides *AF at baseline: according to the stratification factor at randomization. Characteristic Incidence/Mean Value Patient age <65 years 19% 65-74 years 40% ≥ 75 years 42% Female gender 47% Hypertension 86% Mean systolic blood pressure 134 mmHg AF at baseline* 25% History of cardioversion 34%
  • ATHENA Trial: Baseline Characteristics JCE 2008; 19.1/Heart Rhythm 2008 Copyleft Clinical Trial Results. You Must Redistribute Slides **Structural heart disease: coronary heart disease and/or ischemic dilated cardiomyopathy and/or nonischemic dilated cardiomyopathy and/or rheumatic valvular heart disease and/or nonrheumatic valvular heart disease and/or hypertrophic cardiomyopathy and/or history of congestive heart failure and/or left ventricular ejection fraction (LVEF) < 45%. Characteristic Incidence/Mean Value Structural heart disease** 60% -History of coronary artery disease 30% -Ischemic dilated cardiomyopathy 5% -Nonischemic dilated cardiomyopathy 4% -Rheumatic valve disease 2% -Nonrheumatic valve disease 15%
  • ATHENA Trial: Baseline Characteristics JCE 2008; 19.1/Heart Rhythm 2008 Copyleft Clinical Trial Results. You Must Redistribute Slides ***Lone atrial fibrillation: patients without hypertension and without structural heart disease. Characteristic Incidence/Mean Value Structural heart disease cont.** 60% - Hypertrophic cardiomyopathy 2% - History of congestive heart failure 29% - LVEF < 0.45 12% Lone atrial fibrillation*** 6%
  • ATHENA Trial: Primary Endpoint Results
    • Multaq ® (dronedarone) decreased the risk of cardiovascular hospitalizations or death from any cause by 24% (p<0.001).
    Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm 2008
  • ATHENA Trial: Secondary Endpoint Results
    • Compared to placebo, Multaq ® (dronedarone) significantly decreased the risk of cardiovascular death by 30% (p=0.034).
    • Multaq ® (dronedarone) was associated with numerically fewer deaths from any cause (16%, p=0.17).
    • First cardiovascular hospitalization was reduced by 25% (p=<0.001).
    Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm 2008
  • ATHENA Trial: Other Outcomes
    • Death from arrhythmias was reduced by 45% (p=0.01) when patients were treated with Multaq ® (dronedarone).
    • Multaq ® (dronedarone) demonstrated a lower risk of pro-arrhythmia than placebo and no excess of hospitalizations for congestive heart failure.
    • The rate of study drug discontinuation was similar between the two study arms.
    Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm 2008
  • ATHENA Trial: Adverse Events
    • There was a higher frequency of reported gastro-intestinal complications in the Multaq ® (dronedarone) group than in the placebo arm.
    Gastro-intestinal Effects (%) Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm 2008
  • ATHENA Trial: Adverse Events
    • Multaq ® (dronedarone) was associated with a more frequent occurrence of skin disorders as compared to placebo.
    Skin disorders (mainly rash) (%) Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm 2008
  • ATHENA Trial: Adverse Events
    • Patients treated with Multaq ® (dronedarone) demonstrated increased serum creatinine more frequently than those given placebo.
    Increased Blood Creatinine (%) Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm 2008
  • ATHENA Trial: Limitations
    • Future trials should consider patients under 75 years of age without additional cardiovascular risk factors and those with decompensated heart failure.
    • The exclusion of these patients from this study limits the applicability of the results.
    JCE 2008; 19.1/Heart Rhythm 2008
  • ATHENA Trial: Summary
    • Multaq ® (dronedarone) has been discovered as the first safe drug to benefit patients with atrial fibrillation.
    • Findings include decreased rates of cardiovascular hospitalization and mortality.
    JCE 2008; 19.1/Heart Rhythm 2008