Heart Rhythm Drug Increases Risk of Death for Some Patients in Halted Study

Heart Rhythm Drug Increases Risk of Death for Some Patients in Halted Study
American Heart Association Late-Breaking Meeting Report - Abstract: 19068 

Study Highlights: , Nov 14, 2011 (GlobeNewswire via COMTEX) -- Dronedarone, a drug used to treat people with intermittent atrial fibrillation, doubled the risk of death and serious cardiovascular disorders in a study of patients with permanent AF. -- Because of these early findings, researchers ended the study with only 30 percent of the 10,800 intended patients enrolled.

ORLANDO, Fla., Nov. 14, 2011 (GLOBE NEWSWIRE) -- A drug used successfully to treat people with intermittent atrial fibrillation, an abnormal heart rhythm, 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.

Atrial fibrillation (AF), which occurs when the two upper heart chambers beat erratically, affects about 2.7 million Americans. The heart may return to normal rhythm on its own in some people with intermittent or non-permanent AF. For those with permanent AF, it does not. Permanent AF is usually managed with heart rate-controlling medications.

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."

Disclosures are here: http://newsroom.heart.org/pr/aha/document/Disclosures_for_LBCT.xlsx .

Sanofi-Aventis funded the study.

Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The association makes no representation or warranty as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.heart.org/corporatefunding .

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This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: American Heart Association


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