A drug used successfully to treat people with intermittent atrial fibrillation (AF) was unexpectedly dangerous for some patients with a permanent form of the condition, according to late-breaking research presented at the American Heart Association's Scientific Sessions 2011. The study is simultaneously published in the New England Journal of Medicine.

Dronedarone is an anti-arrhythmic drug used for patients with non-permanent AF to reduce AF recurrence and to lower the chances of being hospitalized for heart problems. It is not approved for permanent AF.

"No previous trials have investigated interventions to reduce morbidity and mortality in patients with permanent AF, a high-risk population," said Stuart J. Connolly, M.D., lead author of the study and professor of cardiology at McMaster University in Hamilton, Ontario, Canada.

In July, researchers stopped enrollment into a randomized clinical trial of dronedarone in patients with permanent AF when their data and safety monitoring board detected excessive serious vascular events and deaths in the drug-treated patients. PALLAS (Permanent Atrial fibriLLAtion outcome Study using Dronedarone on top of standard therapy) included only 3,236 of the planned 10,800 patients before researchers stopped recruiting and treatment.

"The message is that the drug dronedarone should not be used for permanent atrial fibrillation," Connolly said.

PALLAS patients, all 65 years or older with permanent AF and other risk factors for vascular events, were randomized to either dronedarone or placebo.

Among the findings reported:

• Overall risk of major vascular events such as stroke, heart attack or death from cardiovascular causes was 2.2 times greater on dronedarone than on placebo: 43 dronedarone patients and 19 on placebo suffered a stroke, heart attack, systemic blood clot or cardiovascular death.
• Twenty-one cardiovascular deaths occurred among dronedarone patients and 10 in the placebo arm.
• Thirteen arrhythmia deaths occurred in the drug group and four in the control group.
• Twenty-two treated patients had strokes - 2.5 times more than the nine strokes in people on placebo.
• Dronedarone increased the risk of heart failure hospitalization.
• Dronedarone patients taking the heart rhythm drug digitalis before accrual - almost one-third of those treated - had a 36 percent increase in their digitalis blood levels.

"There is evidence that this increase in digitalis played a causative role in the increased risk of cardiovascular death," Connolly said. "But this does not explain the increase in stroke or heart failure."

Sanofi-Aventis funded the study.