113342211

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113342211

  1. 1. ATHENA Trial<br />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)<br />Presented at Heart Rhythm 2008 in San Francisco, USA<br /> Presented by Stefan H. Hohnloser, MD<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />
  2. 2. ATHENA Trial: Background<br />Atrial fibrillation (AF) impairs patients’ lives, leading to increased risks of cardiovascular complications.<br />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. <br />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.<br /> JCE 2008; 19.1/Heart Rhythm 2008<br />
  3. 3. ATHENA Trial: Dronedarone<br />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. <br />Unlike amiodarone, this drug does not contain iodine radical and hence does not result in adverse effects on thyroid and lung functions.<br /> JCE 2008; 19.1/Heart Rhythm 2008<br />
  4. 4. ATHENA Trial: Study Design<br />4,628 patients &gt;75 years with atrial fibrillation or 70-75 years with atrial fibrillation and at least one additional cardiovascular risk factor prior to randomization. <br />Double blind. Randomized. Placebo controlled. International multicenter. Mean follow-up 21 months. <br />R<br />Multaq® (dronedarone)<br />400 mg BID<br />Placebo<br />12-30 mos. follow-up<br /><ul><li>Primary Endpoint: composite of all-cause mortality combined with cardiovascular hospitalization
  5. 5. Secondary Endpoint: death from any cause, cardiovascular death, hospitalization for cardiovascular reasons</li></ul>Copyleft Clinical Trial Results. You Must Redistribute Slides<br /> JCE 2008; 19.1/Heart Rhythm 2008<br />
  6. 6. ATHENA Trial: Inclusion Criteria<br />≥75 yrs with or without additional risk factors<br />≥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 &lt; 0.40 by 2D-echocardiography.<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  7. 7. ATHENA Trial: Inclusion Criteria Cont.<br />Availability of one 12-lead ECG within the last 6 months, indicating prior or current AF/A flutter<br />Access to a second 12-lead ECG within the last 6 months showing prior or current SR<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  8. 8. ATHENA Trial: Exclusion Criteria<br />Presence of one of the following cardiac conditions:<br />Permanent AF<br />Unstable hemodynamic situation (i.e., recently decompensated heart failure)<br />Congestive heart failure NYHA class IV<br />Planned major non-cardiac or cardiac surgery<br />Acute myocarditis<br />Bradycardia &lt; 50 bpm and/or a PR interval &gt; 0.28 seconds<br />Significant sinus node disease in the past, if not treated with a pacemaker <br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  9. 9. ATHENA Trial: Exclusion Criteria cont.<br />Refusal or inability to give informed consent<br />Any non-cardiac severe illness limiting life expectancy <br />Pregnancy and breast feeding<br />Women of child-bearing potential without adequate birth control<br />Participation in another clinical trial<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  10. 10. ATHENA Trial: Exclusion Criteria cont.<br />A calculated GFR at baseline &lt; 10mL/min using the Cockroft Gault formula <br />Potassium level &lt; 3.5 mmol/L if not corrected<br />Need for concomitant medication prohibited within ATHENA (i.e., other antiarrhythmic drugs of Vaughan-Williams class I or III)<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  11. 11. ATHENA Trial: Baseline Characteristics<br />*AF at baseline: according to the stratification factor at randomization.<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1 /Heart Rhythm 2008<br />
  12. 12. ATHENA Trial: Baseline Characteristics<br />**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) &lt; 45%.<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  13. 13. ATHENA Trial: Baseline Characteristics<br />***Lone atrial fibrillation: patients without hypertension and without structural heart disease.<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  14. 14. ATHENA Trial: Primary Endpoint Results<br />Multaq® (dronedarone) decreased the risk of cardiovascular hospitalizations or death from any cause by 24% (p&lt;0.001).<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  15. 15. ATHENA Trial: Secondary Endpoint Results<br />Compared to placebo, Multaq® (dronedarone) significantly decreased the risk of cardiovascular death by 30% (p=0.034).<br />Multaq® (dronedarone) was associated with numerically fewer deaths from any cause (16%, p=0.17).<br />First cardiovascular hospitalization was reduced by 25% (p=&lt;0.001).<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  16. 16. ATHENA Trial: Other Outcomes<br />Death from arrhythmias was reduced by 45% (p=0.01) when patients were treated with Multaq® (dronedarone).<br />Multaq® (dronedarone) demonstrated a lower risk of pro-arrhythmia than placebo and no excess of hospitalizations for congestive heart failure.<br />The rate of study drug discontinuation was similar between the two study arms.<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  17. 17. ATHENA Trial: Adverse Events<br /><ul><li>There was a higher frequency of reported gastro-intestinal complications in the Multaq® (dronedarone) group than in the placebo arm.</li></ul> Gastro-intestinal Effects (%)<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  18. 18. ATHENA Trial: Adverse Events<br /><ul><li>Multaq® (dronedarone) was associated with a more frequent occurrence of skin disorders as compared to placebo.</li></ul>Skin disorders (mainly rash) (%)<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  19. 19. ATHENA Trial: Adverse Events<br /><ul><li>Patients treated with Multaq® (dronedarone) demonstrated increased serum creatinine more frequently than those given placebo. </li></ul> Increased Blood Creatinine (%)<br />Copyleft Clinical Trial Results. You Must Redistribute Slides<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  20. 20. ATHENA Trial: Limitations<br />Future trials should consider patients under 75 years of age without additional cardiovascular risk factors and those with decompensated heart failure.<br />The exclusion of these patients from this study limits the applicability of the results.<br />JCE 2008; 19.1/Heart Rhythm 2008<br />
  21. 21. ATHENA Trial: Summary<br />Multaq® (dronedarone) has been discovered as the first safe drug to benefit patients with atrial fibrillation.<br />Findings include decreased rates of cardiovascular hospitalization and mortality.<br />JCE 2008; 19.1/Heart Rhythm 2008<br />

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