Dronedarone Slashes Hospital Days in Atrial Fib

NEW ORLEANS — Patients with atrial fibrillation who were treated with the investigational antiarrhythmic agent dronedarone spent 35% fewer total days in the hospital for cardiovascular reasons than did patients in the placebo arm of the landmark phase III ATHENA trial.

Moreover, the dronedarone group spent 47% fewer days in intensive care or coronary care units and 45% fewer days in midlevel care units. Those differences will add up to serious cost savings favoring dronedarone when an ongoing ATHENA cost-effectiveness analysis is completed, Dr. Christian Torp-Pedersen said at the annual scientific sessions of the American Heart Association.

Dronedarone also reduced by 28% the total number of days of hospitalization for all causes—cardiovascular as well as noncardiovascular—reaffirming the drug's relatively benign safety profile as seen in earlier studies. If dronedarone were associated with significant pulmonary, dermatologic, thyroid, or other toxicities—as is true of its structural relative amiodarone—the dronedarone group would have had more hospital time for noncardiovascular reasons than the placebo group, observed Dr. Torp-Pedersen of Gentofte University Hospital, Copenhagen.

ATHENA was a double-blind randomized trial that involved 4,628 patients with paroxysmal or persistent atrial fibrillation or atrial flutter in 37 countries. The patients received 400 mg b.i.d. of dronedarone (Multaq) or placebo and were followed for a mean of 21 months. The participants had to be either at least 75 years old or aged 70 or older with comorbid diabetes, hypertension, low left ventricular ejection fraction, enlarged left atrial size, or prior stroke.

The primary results of ATHENA were presented at the 2008 annual meeting of the Heart Rhythm Society. The risk of the combined primary end point of all-cause mortality or cardiovascular hospitalization was reduced by 24% in the dronedarone arm.

Dr. Torp-Pedersen presented a secondary post hoc analysis of the ATHENA data that focused on dronedarone's impact upon the total hospitalization burden. During the 21 months of follow-up, the dronedarone group collectively spent nearly 4,000 fewer days in the hospital. (See box.)

What's particularly intriguing, he observed, is that the dronedarone group showed a consistent trend for fewer cardiovascular hospitalizations for reasons other than atrial fibrillation as well as for atrial fibrillation. The dronedarone-treated patients were not only 37% less likely to be admitted for atrial fibrillation, they were also 14% less likely to be hospitalized for cardiovascular reasons unrelated to atrial fibrillation. They were also 30% less likely than the control group to be admitted for acute coronary syndrome. All of these differences were statistically significant.

The dronedarone group's 14% relative risk reduction in heart failure admissions did not achieve significance because of the limited number of patients in the analysis, since only 20% of ATHENA participants had heart failure at baseline. Still, this trend for fewer heart failure hospitalizations is welcome news, Dr. Torp-Pedersen said, because an earlier, smaller clinical trial was halted early because of an apparent increase in deaths among dronedarone-treated patients with New York Heart Association class IV heart failure. Patients with class IV heart failure were excluded from ATHENA.

A likely explanation for dronedarone's ability to reduce cardiovascular admissions not related to atrial fibrillation involves the drug's dual effects: It is both a rhythm- and a rate-control drug. Dronedarone reduced the mean heart rate during atrial fibrillation episodes to 78 beats per minute, as compared with 87 bpm with placebo, Dr. Torp-Pedersen noted.

Although dronedarone was similarly safe and effective in ATHENA participants with class II and class III heart failure, Dr. Torp-Pedersen said that in clinical practice, he'd be cautious in using it in patients with class III heart failure. Dr. Torp-Pedersen is on the ATHENA steering committee and has received research grants and consulting fees from Sanofi-Aventis, which is developing dronedarone.

The only adverse effect that was more common with dronedarone than with placebo in the trial was an elevated serum creatinine level, which occurred in 4.7% of the dronedarone group and 1% on placebo.

Audience concerns focused on using dronedarone in patients with heart failure, a common comorbidity in patients with atrial fibrillation.

“How is this going to play out in clinical practice?” asked session moderator Dr. Sana Al Khatib of Duke University, Durham, N.C. “NYHA class is variable. A patient with class II heart failure can go into class III in a few months. Are you suggesting that we can give this drug to patients with mild heart failure and as soon as they go into class III, we have to stop the drug until we control their symptoms?”

“That's going to be a dilemma for a group of patients: When is the heart failure severe enough to cause an exclusion? There's no simple answer,” Dr. Torp-Pedersen replied. “There may be particular reasons why an individual absolutely can't tolerate amiodarone, and in that patient you'd go a bit further with dronedarone. And if a patient readily tolerates amiodarone, you might be tempted to switch to it when heart failure worsens. I think that will be the scenario in real life.”

The Food and Drug Administration in August 2006 turned down a request for approval that had relied on two previous trials using a combined end point of all-cause hospitalizations or deaths. In August 2008, the company resubmitted its application for marketing approval based on the ATHENA results and has been granted a priority review; a decision from the FDA is expected in early 2009. Dronedarone is also under regulatory review by the European Medicines Agency.

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — Patients with atrial fibrillation who were treated with the investigational antiarrhythmic agent dronedarone spent 35% fewer total days in the hospital for cardiovascular reasons than did patients in the placebo arm of the landmark phase III ATHENA trial.

Moreover, the dronedarone group spent 47% fewer days in intensive care or coronary care units and 45% fewer days in midlevel care units. Those differences will add up to serious cost savings favoring dronedarone when an ongoing ATHENA cost-effectiveness analysis is completed, Dr. Christian Torp-Pedersen said at the annual scientific sessions of the American Heart Association.

Dronedarone also reduced by 28% the total number of days of hospitalization for all causes—cardiovascular as well as noncardiovascular—reaffirming the drug's relatively benign safety profile as seen in earlier studies. If dronedarone were associated with significant pulmonary, dermatologic, thyroid, or other toxicities—as is true of its structural relative amiodarone—the dronedarone group would have had more hospital time for noncardiovascular reasons than the placebo group, observed Dr. Torp-Pedersen of Gentofte University Hospital, Copenhagen.

ATHENA was a double-blind randomized trial that involved 4,628 patients with paroxysmal or persistent atrial fibrillation or atrial flutter in 37 countries. The patients received 400 mg b.i.d. of dronedarone (Multaq) or placebo and were followed for a mean of 21 months. The participants had to be either at least 75 years old or aged 70 or older with comorbid diabetes, hypertension, low left ventricular ejection fraction, enlarged left atrial size, or prior stroke.

The primary results of ATHENA were presented at the 2008 annual meeting of the Heart Rhythm Society. The risk of the combined primary end point of all-cause mortality or cardiovascular hospitalization was reduced by 24% in the dronedarone arm.

Dr. Torp-Pedersen presented a secondary post hoc analysis of the ATHENA data that focused on dronedarone's impact upon the total hospitalization burden. During the 21 months of follow-up, the dronedarone group collectively spent nearly 4,000 fewer days in the hospital. (See box.)

What's particularly intriguing, he observed, is that the dronedarone group showed a consistent trend for fewer cardiovascular hospitalizations for reasons other than atrial fibrillation as well as for atrial fibrillation. The dronedarone-treated patients were not only 37% less likely to be admitted for atrial fibrillation, they were also 14% less likely to be hospitalized for cardiovascular reasons unrelated to atrial fibrillation. They were also 30% less likely than the control group to be admitted for acute coronary syndrome. All of these differences were statistically significant.

The dronedarone group's 14% relative risk reduction in heart failure admissions did not achieve significance because of the limited number of patients in the analysis, since only 20% of ATHENA participants had heart failure at baseline. Still, this trend for fewer heart failure hospitalizations is welcome news, Dr. Torp-Pedersen said, because an earlier, smaller clinical trial was halted early because of an apparent increase in deaths among dronedarone-treated patients with New York Heart Association class IV heart failure. Patients with class IV heart failure were excluded from ATHENA.

A likely explanation for dronedarone's ability to reduce cardiovascular admissions not related to atrial fibrillation involves the drug's dual effects: It is both a rhythm- and a rate-control drug. Dronedarone reduced the mean heart rate during atrial fibrillation episodes to 78 beats per minute, as compared with 87 bpm with placebo, Dr. Torp-Pedersen noted.

Although dronedarone was similarly safe and effective in ATHENA participants with class II and class III heart failure, Dr. Torp-Pedersen said that in clinical practice, he'd be cautious in using it in patients with class III heart failure. Dr. Torp-Pedersen is on the ATHENA steering committee and has received research grants and consulting fees from Sanofi-Aventis, which is developing dronedarone.

The only adverse effect that was more common with dronedarone than with placebo in the trial was an elevated serum creatinine level, which occurred in 4.7% of the dronedarone group and 1% on placebo.

Audience concerns focused on using dronedarone in patients with heart failure, a common comorbidity in patients with atrial fibrillation.

“How is this going to play out in clinical practice?” asked session moderator Dr. Sana Al Khatib of Duke University, Durham, N.C. “NYHA class is variable. A patient with class II heart failure can go into class III in a few months. Are you suggesting that we can give this drug to patients with mild heart failure and as soon as they go into class III, we have to stop the drug until we control their symptoms?”

“That's going to be a dilemma for a group of patients: When is the heart failure severe enough to cause an exclusion? There's no simple answer,” Dr. Torp-Pedersen replied. “There may be particular reasons why an individual absolutely can't tolerate amiodarone, and in that patient you'd go a bit further with dronedarone. And if a patient readily tolerates amiodarone, you might be tempted to switch to it when heart failure worsens. I think that will be the scenario in real life.”

The Food and Drug Administration in August 2006 turned down a request for approval that had relied on two previous trials using a combined end point of all-cause hospitalizations or deaths. In August 2008, the company resubmitted its application for marketing approval based on the ATHENA results and has been granted a priority review; a decision from the FDA is expected in early 2009. Dronedarone is also under regulatory review by the European Medicines Agency.

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — Patients with atrial fibrillation who were treated with the investigational antiarrhythmic agent dronedarone spent 35% fewer total days in the hospital for cardiovascular reasons than did patients in the placebo arm of the landmark phase III ATHENA trial.

Moreover, the dronedarone group spent 47% fewer days in intensive care or coronary care units and 45% fewer days in midlevel care units. Those differences will add up to serious cost savings favoring dronedarone when an ongoing ATHENA cost-effectiveness analysis is completed, Dr. Christian Torp-Pedersen said at the annual scientific sessions of the American Heart Association.

Dronedarone also reduced by 28% the total number of days of hospitalization for all causes—cardiovascular as well as noncardiovascular—reaffirming the drug's relatively benign safety profile as seen in earlier studies. If dronedarone were associated with significant pulmonary, dermatologic, thyroid, or other toxicities—as is true of its structural relative amiodarone—the dronedarone group would have had more hospital time for noncardiovascular reasons than the placebo group, observed Dr. Torp-Pedersen of Gentofte University Hospital, Copenhagen.

ATHENA was a double-blind randomized trial that involved 4,628 patients with paroxysmal or persistent atrial fibrillation or atrial flutter in 37 countries. The patients received 400 mg b.i.d. of dronedarone (Multaq) or placebo and were followed for a mean of 21 months. The participants had to be either at least 75 years old or aged 70 or older with comorbid diabetes, hypertension, low left ventricular ejection fraction, enlarged left atrial size, or prior stroke.

The primary results of ATHENA were presented at the 2008 annual meeting of the Heart Rhythm Society. The risk of the combined primary end point of all-cause mortality or cardiovascular hospitalization was reduced by 24% in the dronedarone arm.

Dr. Torp-Pedersen presented a secondary post hoc analysis of the ATHENA data that focused on dronedarone's impact upon the total hospitalization burden. During the 21 months of follow-up, the dronedarone group collectively spent nearly 4,000 fewer days in the hospital. (See box.)

What's particularly intriguing, he observed, is that the dronedarone group showed a consistent trend for fewer cardiovascular hospitalizations for reasons other than atrial fibrillation as well as for atrial fibrillation. The dronedarone-treated patients were not only 37% less likely to be admitted for atrial fibrillation, they were also 14% less likely to be hospitalized for cardiovascular reasons unrelated to atrial fibrillation. They were also 30% less likely than the control group to be admitted for acute coronary syndrome. All of these differences were statistically significant.

The dronedarone group's 14% relative risk reduction in heart failure admissions did not achieve significance because of the limited number of patients in the analysis, since only 20% of ATHENA participants had heart failure at baseline. Still, this trend for fewer heart failure hospitalizations is welcome news, Dr. Torp-Pedersen said, because an earlier, smaller clinical trial was halted early because of an apparent increase in deaths among dronedarone-treated patients with New York Heart Association class IV heart failure. Patients with class IV heart failure were excluded from ATHENA.

A likely explanation for dronedarone's ability to reduce cardiovascular admissions not related to atrial fibrillation involves the drug's dual effects: It is both a rhythm- and a rate-control drug. Dronedarone reduced the mean heart rate during atrial fibrillation episodes to 78 beats per minute, as compared with 87 bpm with placebo, Dr. Torp-Pedersen noted.

Although dronedarone was similarly safe and effective in ATHENA participants with class II and class III heart failure, Dr. Torp-Pedersen said that in clinical practice, he'd be cautious in using it in patients with class III heart failure. Dr. Torp-Pedersen is on the ATHENA steering committee and has received research grants and consulting fees from Sanofi-Aventis, which is developing dronedarone.

The only adverse effect that was more common with dronedarone than with placebo in the trial was an elevated serum creatinine level, which occurred in 4.7% of the dronedarone group and 1% on placebo.

Audience concerns focused on using dronedarone in patients with heart failure, a common comorbidity in patients with atrial fibrillation.

“How is this going to play out in clinical practice?” asked session moderator Dr. Sana Al Khatib of Duke University, Durham, N.C. “NYHA class is variable. A patient with class II heart failure can go into class III in a few months. Are you suggesting that we can give this drug to patients with mild heart failure and as soon as they go into class III, we have to stop the drug until we control their symptoms?”

“That's going to be a dilemma for a group of patients: When is the heart failure severe enough to cause an exclusion? There's no simple answer,” Dr. Torp-Pedersen replied. “There may be particular reasons why an individual absolutely can't tolerate amiodarone, and in that patient you'd go a bit further with dronedarone. And if a patient readily tolerates amiodarone, you might be tempted to switch to it when heart failure worsens. I think that will be the scenario in real life.”

The Food and Drug Administration in August 2006 turned down a request for approval that had relied on two previous trials using a combined end point of all-cause hospitalizations or deaths. In August 2008, the company resubmitted its application for marketing approval based on the ATHENA results and has been granted a priority review; a decision from the FDA is expected in early 2009. Dronedarone is also under regulatory review by the European Medicines Agency.

ELSEVIER GLOBAL MEDICAL NEWS