ATHENA Trial: Presented at Heart Rhythm 2008 in San Francisco, USA Presented by Stefan H. Hohnloser, MD

ATHENA Trial
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
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.
Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm 2008
ATHENA Trial: Dronedarone
• 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: Study Design
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.
R
Multaq® (dronedarone) Placebo

400 mg BID
12-30 mos. follow-up


Primary Endpoint: composite of all-cause mortality combined
with cardiovascular hospitalization

Secondary Endpoint: death from any cause, cardiovascular
death, hospitalization for cardiovascular reasons
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.
Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1/Heart Rhythm
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
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
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
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)
ATHENA Trial: Baseline Characteristics
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%
*AF at baseline: according to the stratification factor at
randomization.
Copyleft Clinical Trial Results. You Must Redistribute Slides JCE 2008; 19.1 /Heart Rhythm 2008
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%
**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%.
Structural heart disease cont.** 60%

- Hypertrophic cardiomyopathy 2%
- History of congestive heart failure 29%
- LVEF < 0.45 12%
Lone atrial fibrillation*** 6%
***Lone atrial fibrillation: patients without hypertension and without structural heart disease.
ATHENA Trial: Primary Endpoint Results
Multaq® (dronedarone) decreased the risk of

cardiovascular hospitalizations or death
from any cause by 24% (p<0.001).
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).
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.
ATHENA Trial: Adverse Events
• There was a higher

Gastro-intestinal Effects (%)
30%
26.0% frequency of reported
25% gastro-intestinal
22.0%
complications in the
20% Multaq® (dronedarone)
group than in the placebo
15% arm.
10%
5%
0%
Placebo Multaq®
(dronedarone)
Skin disorders (mainly rash) (%)
10.0% • Multaq® (dronedarone)

10%
was associated with a
8.0% more frequent
occurrence of skin
disorders as compared to
placebo.
5%
0%
Placebo Multaq®
(dronedarone)
Increased Blood Creatinine (%)
4.7% • Patients treated with

5%
Multaq® (dronedarone)
demonstrated increased
4% serum creatinine more
frequently than those
3% given placebo.
2%
1.0%
1%
0%
Placebo Multaq®
(dronedarone)
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.
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.

ATHENA Trial: Presented at Heart Rhythm 2008 in San Francisco, USA Presented by Stefan H. Hohnloser, MD

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ATHENA Trial: Presented at Heart Rhythm 2008 in San Francisco, USA Presented by Stefan H. Hohnloser, MD

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Авторское право:

Доступные форматы

ATHENA Trial

(A placebo-controlled, double-blind, parallel arm Trial to

Presented at Heart Rhythm 2008 in San

Copyleft Clinical Trial Results. You Must Redistribute Slides

• Atrial fibrillation (AF) impairs patients’ lives, leading to increased

• Over the course of 20 years of clinical drug trials in AF no drug has

• ATHENA set out to evaluate the effect of Multaq® (dronedarone), a

• Dronedarone (Multaq®) manufactured by Sanofi-

• Unlike amiodarone, this drug does not contain

Multaq® (dronedarone) Placebo

12-30 mos. follow-up

• ≥75 yrs with or without additional risk factors

• ≥70 yrs with at least one of the following risk

• Availability of one 12-lead ECG within the

• Access to a second 12-lead ECG within the

Presence of one of the following cardiac conditions:

• Refusal or inability to give informed consent

• A calculated GFR at baseline < 10mL/min using

• Potassium level < 3.5 mmol/L if not corrected

• Need for concomitant medication prohibited within

Characteristic Incidence/Mean Value

Characteristic Incidence/Mean Value

Structural heart disease** 60%

Characteristic Incidence/Mean Value

Structural heart disease cont.** 60%

Multaq® (dronedarone) decreased the risk of

• Compared to placebo, Multaq® (dronedarone)

• Multaq® (dronedarone) was associated with numerically

• First cardiovascular hospitalization was reduced by 25%

• Death from arrhythmias was reduced by 45% (p=0.01)

• Multaq® (dronedarone) demonstrated a lower risk of pro-

• The rate of study drug discontinuation was similar

• There was a higher

10.0% • Multaq® (dronedarone)

4.7% • Patients treated with

• Future trials should consider patients under 75

• The exclusion of these patients from this study

• Multaq® (dronedarone) has been discovered

• Findings include decreased rates of

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