抗不整脈薬が一部の患者に対して危険であることが証明された（Abstract # 19068）

PALLAS：Dronedaroneは慢性AF患者の重篤な血管イベントおよび死亡のリスクを増加させる

PALLAS: Dronedarone increases risk of serious vascular events and death in patients with permanent AF

間欠性心房細動（AF）患者の治療に成功している薬剤dronedaroneは慢性心房細動患者の一部においては予想外に危険であるとのlate-breaking researchの結果が2011年American Heart Association学会で発表され、同時にNew England Journal of Medicineに掲載された。PALLAS（Permanent Atrial fibriLLAtion outcome Study using Dronedarone on top of standard therapy　慢性心房細動の標準治療にdronedaroneを加えたアウトカムスタディ）トライアルの参加者は、全員が慢性AFを有する65歳以上で血管イベントの他のリスクファクターを有していた。彼らはdronedaroneまたプラセボ投与群に無作為に割り付けられた。実薬治療群において過剰に重篤な血管イベントや死亡がデータ安全性監視委員会により検出された場合には組み入れが中止された。脳卒中、心筋梗塞（MI）、または心血管死亡などの重大な血管イベントは、プラセボ群よりdronedarone群において2.2倍多かった：dronedarone群の患者43人およびプラセボ群患者の19人において脳卒中、MI、全身性血栓症または心血管死が発現した。これらの結果が早期に明らかとなったため、このスタディは組み入れ予定人数の10,800人のうちわずか30%を組み入れた段階で中止された。筆者らは、dronedaroneは慢性心房細動患者には使用すべきでないと忠告している。

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.