全球制药巨头赛诺菲-安万特集团对外宣布，美国食品药品监督管理局（FDA）已批准Multaq®（决奈达隆）400毫克片剂上市，用于房颤/房扑患者的治疗。据悉，该药目前已在中国多家医院进行临床试验。
“决奈达隆已获批在美国上市，目前正在中国一些医院进行临床试验。”赛诺菲-安万特中国公司市场部总监龙爱晶博士向腾讯财经表示，公司已向国家食品药品监督管理局提交上市申请，何时能在中国正式推出尚须时日。
据了解，美国食品药品监督管理局近日批准赛诺菲-安万特研发的Multaq®（决奈达隆）400 毫克片剂上市，用于房颤/房扑患者的治疗。Multaq®获得FDA的批准是基于一系列（共招募近6300名患者）的国际多中心、随机临床试验结果。
知名心血管病专家胡大一教授称，作为一种常见的疾病，目前房颤已成为公共卫生难题，对患者及家属造成严重影响，但早期发现和治疗能降低出现严重心血管并发症的风险。胡大一呼吁，医疗专业人员提高疾病认知，加强患者教育。
一项国际调研调查结果显示，患者对房颤及其后果和治疗手段缺乏了解，该调查覆盖了包括中国在内的11个国家的1600名心脏病专家和患者。调研中有1/4的患者不理解或不能解释何为房颤，只有1/3的患者为房颤感到担忧。以往研究显示，心律不齐导致住院病例中房颤占1/3，调研结果指出，房颤患者一年中就诊次数接近9次。
黄德嘉表示，过去二十年间房颤/房扑治疗领域的新药寥寥无几，Multaq®的出现能降低房颤或房扑患者因心血管事件住院的风险，治疗房颤或房扑的方式有望从此改变。
问题：决奈达隆能否降低心血管事件风险？
方法：在这一双盲研究中，4628例伴有≥1个死亡危险因素（例如年龄>75岁、高血压、糖尿病）的心房颤动（AF）患者（平均年龄72岁）被随机分配，接受决奈达隆400 mg一日两次（n = 2301）或安慰剂（n = 2327）治疗。排除心功能IV级的心力衰竭 （HF）患者。对所有患者随访≥1年（平均21个月）。主要结果为第一次因心血管事件住院治疗或全因死亡。
结果：随访结果的发生率在决奈达隆组比安慰剂组显著更低：主要结果（32% vs. 39%），第一次因心血管事件住院治疗（29% vs. 37%），第一次因AF住院治疗（15% vs. 22%），心血管死亡（2.7% vs. 3.9%），心律不齐所致死亡（1.1% vs. 2.1%）。决奈达隆治疗因为不良事件比安慰剂更多见（12.7% vs. 8.1%）而被终止。没有肺、甲状腺或肝毒性的证据。
结论：决奈达隆降低了AF患者严重心血管事件的风险。
评论：决奈达隆在结构上与胺碘酮相似，但不含碘。决奈达隆相对于胺碘酮的主要优势是半衰期短（24小时），且缺乏重要器官毒性。一项比较胺碘酮和决奈达隆的是随机研究正在进行中。但是，即使证明决奈达隆在AF的预防上没有胺碘酮有效，由于其没有器官毒性的风险，它将有可能大量取代胺碘酮治疗AF。一个例外是在严重心力衰竭的患者亚组中，决奈达隆可能增高死亡率，而胺碘酮却不会。
决奈达隆，新一代胺碘酮类药物，心血管病用药。其分子结构与胺碘酮类似，但不含碘，因此长期应用该药，被认为较胺碘酮更为安全。
2006年底开始的双盲对照的ATHENA研究纳入4628例患者,比较决奈达隆与安慰剂预防房颤、房扑患者住院和全因死亡的疗效差异。随访1年后发现,与接受安慰剂者相比,接受决奈达隆治疗者的心血管住院风险和全因死亡率显著降低了24.2%,心血管死亡率和首次心血管住院率显著降低了30%和25.5%。
似乎给我们提供了一个很好的治疗房颤等心律失常的武器，但昨天新英格兰医学杂志一篇来自哥本哈根的研究报告告诉我们,他们用这个药物治疗有心衰症状及严重左心收缩功能不全患者的研究被迫中止。因为仅仅随访2个月，决奈达隆组的死亡率8.1%就显著高于对照组3.8%，共入选627位病人。药物用量400mg/天，一天两次。另外，血肌酐水平增高作为严重不良反应也明显高于对照组。他们的结论至少提示：严重心衰和左心收缩功能不全患者，用决奈达隆治疗可能增加患者因心衰加重所致的早期死亡风险。
决奈达隆在心房颤动药物治疗中的现状
决奈达隆是一种有效的治疗房扑/房颤的药物，由于“去碘化”而无甲状腺和肺毒性，成为抗心律失常治疗的一个新型的更安全有效的武器。
□大连医科大学附属第一医院 李世军 杨延宗
心房颤动（房颤）是最常见的心律失常，随着年龄的增加发生率增高。目前，抗心律失常药物有效性不高，存在潜在的促心律失常作用以及治疗相关的毒副作用，在临床应用中明显受限。
决奈达隆（dronedarone）是一种无碘的苯并呋喃衍生物，其抗心律失常药理特性与胺碘酮相似，但其在侧链苯环3、5位上无碘原子（图1），无明显的甲状腺抑制作用和抑制甲状腺激素作用，同时在组织中的消除半衰期也明显短于胺碘酮，成为新一代III类抗心律失常药物（JohnP. Morrow, Christopher P. 2007），本文就目前决奈达隆在房颤治疗中的现状作一综述。
决奈达隆的分子结构与生物学效应基础研究
决奈达隆为无碘的苯并呋喃衍生物，母链苯并呋喃与胺碘酮相同。与胺碘酮相比，决奈达隆在侧链苯环3、5位上无碘原子，使其保持胺碘酮的多离子通道阻滞特性又克服了对甲状腺及肺脏的毒副作用（NaccarelliGV, Wolbrette DL, Khan M, et al. 2003）。应用决奈达隆后1～4 h可达到最大血浆浓度，其与血浆蛋白结合率可超过98%（Dale KM, White CM.2007）。该药消除半衰期为24 h，给药400 mg/d bid，5～7天后达到药物稳态水平（60～150ng/ml）。由于肝脏的首过效应，决奈达隆的生物利用度为15%，但与食物同服能提高2～3倍血药浓度。
决奈达隆主要经肝脏的首过效应以及细胞色素P450 3A4和CYP2D6酶促系统消除，仅约6%经肾脏清除，其血浆浓度不受肾功能影响（Damy T, PoussetF, Caplain H, et al. 2004；Ohyama K, Nakajima M, Suzuki M, et al. 2004）。
图1. 决奈达隆化学式：N,N-二丁基-3-(4-[2-丁基-5-甲基磺酰胺基]苯并呋喃-3-羰酰苯氧基）丙胺.
1. 心血管作用的基础研究
决奈达隆与胺碘酮相似，是一种多通道阻滞剂，具有I、II、III、IV类抗心律失常药物作用。Lalevee等(Lalevee N, Nargeot J, Barrere-Lemarie S, et al. 2003)通过细胞膜片钳技术研究发现，决奈达隆以剂量依赖的方式有效地阻断心房钠通道电子流。在0.3µM浓度下，决奈达隆可以使23%的钠通道电子流阻滞，而在3 µM时可阻滞97%的钠通道电子流。通过对比研究发现，决奈达隆比胺碘酮能更有效地阻滞钠通道。Gautier等(Gautier P, Guillemare E, Marion A, et al. 2003)所进行的基础研究表明，决奈达隆通过阻断心脏K电子流和Na电子流，进而延迟复极时间，延长动作电位间期，具有潜在的抗心律失常疗效，而很少出现致心律失常作用。对于人体的心室肌细胞，3 µM半抑制浓度的决奈达隆可以阻断快速激活延迟整流钾电流（IKr），而在10 µM半抑制浓度下，可有效阻断慢速激活IKr。此外，在0.18micro;M半抑制浓度下，决奈达隆可以有效阻断L型钙通道（L-Ca）。Varro等(Varro A, Takacs J, Nemeth M, et al. 2001)对犬的心室肌细胞研究发现，决奈达隆10micro;M减少L-Ca通道的77%离子内流，同时减少97%的延迟整合钾离子通道IKr。这些发现都证明了决奈达隆是一种多通道的阻滞剂，可以有效阻滞INa、ICa(L)、IKr、IKs及IK1电流。
2. 非心血管作用的基础研究
2.1甲状腺毒性
众多临床试验证明，胺碘酮通过其代谢产物去乙胺碘酮拮抗甲状腺激素受体产生相应的甲状腺症状。一项为期2周的小鼠研究(Ohyama K, Nakajima M, Suzuki M, et al. 2000)结果显示，在体外，决奈达隆阻断T3与TRB1结合，使结合率降至14%，无TRB1阻断；而在体内，胺碘酮显著提高TSH水平，降低rT3和T3水平，高浓度的决奈达隆可降低血浆中T3、T4和TSH浓度，而rT3则保持不变。在另一项相似的研究中(Pantos C, Mourouzis I, Delbruyere M, et al. 2004)，胺碘酮组rT3和rT4均升高，而决奈达隆则不变。
研究结果进一步提示，决奈达隆通过其代谢产物有抵抗TRA1和TRB1的作用，对血浆中甲状腺激素的作用则微乎其微。
2.2 肺毒性
研究表明，胺碘酮和决奈达隆肺毒性可通过对肺泡巨噬细胞的损伤程度进行评价。Quaglino等(Quaglino D, Ha HR, Duner E, et al. 2004)对家兔的研究数据提示了决奈达隆与胺碘酮类似，存在对肺泡巨噬细胞的毒性作用。由于Ⅲ期临床试验没有确切证据证明决奈达隆对人体的肺毒性，关于决奈达隆肺毒性的基础药理体内和体外相关研究还需要进一步深入。
临床研究
1. 预防房颤复发
决奈达隆对房颤电复律后患者具有明确预防房颤复发作用，其抗心律失常作用与用药剂量无相关性。DAFNE研究（Touboul P, Brugada J, Capucci A, et al. 2003）所针对的人群是持续性房颤患者，所有患者在电复律后分别给予决奈达隆400 mg、600 mg、800 mg bid或安慰剂治疗。通过6个月随访发现，决奈达隆400 mg bid组患者房颤的再发时间显著延长（治疗组房颤复发时间平均为60 d，安慰剂组为5.3 d），600 mg及800 mg bid组，房颤的复发率较400 mg bid组无明显差异。
决奈达隆可明确延长阵发性房颤患者窦性心律的维持时间。EURIDIS与ADONIS研究(Singh BN, Connolly SJ, Crijns HJ, et al. 2007)所针对的人群为既往有房颤病史（3个月中至少发作过一次房颤或房扑）的窦性心律患者，采用决奈达隆400mg bid口服，与安慰剂相比，决奈达隆使12个月内房颤和房扑的再发风险分别下降21.6%（EURIDIS）和27.5%（ADONIS）。
决奈达隆在预防房颤复发方面明显优于安慰剂，但其抗心律失常效能与胺碘酮仍有差别。
在DIONYSOS研究中(Sanofi Aventis. 2008)，对房颤患者电复律后服用药物对比发现，决奈达隆组房颤复发率高于胺碘酮组（63.5% vs. 42.0%）。Piccini等(Piccini JP, Hasselblad V, Peterson ED, et al.2009)对4项决奈达隆与安慰剂、4项胺碘酮与安慰剂及1项决奈达隆与胺碘酮对比的荟萃分析发现，在维持窦性心律治疗方面，胺碘酮优于决奈达隆。最近发表的对12项研究的5060例患者荟萃分析(Doyle JF, HoK M. 2009)发现，胺碘酮比安慰剂或一种控制心室率药物在维持窦性心律治疗上更有效，但胺碘酮治疗相关的副作用明显高于其他药物，因不良反应停药率明显增高。
目前共同观点认为，决奈达隆是中等强度的抗心律失常药物，在预防房颤复发治疗方面优于安慰剂，低于胺碘酮，药物相关不良反应及停药率均较低。
2. 控制房颤心室率
决奈达隆在控制房颤的心室率治疗方面安全、有效。ERATO(Davy JM, Herold M, Hoglund C, et al. 2008)是一项针对持续性房颤静息状态下心室率控制的研究，病例涉及欧洲9个国家的35个研究中心，治疗组口服决奈达隆400 mg bid，以安慰剂为对照，采用24 h动态心电图进行评价，随访发现决奈达隆组患者从治疗第14d开始心室率明显减低，并一直持续到第6个月。
而其他相关研究，如DAFNE研究、EURIDIS研究、ADONIS研究及ATHENA研究结果与ERATO研究结果相一致，提示决奈达隆具有良好的控制房颤心室率作用。
3. 对卒中发生的影响
决奈达隆可能对房颤患者卒中的发生产生影响。
Connolly等（Connolly SJ, Crijns HJ,Torp-Pedersen C, et al. 2009）对ATHENA研究卒中分析表明，在应用抗凝或抗血小板药物条件下，应用决奈达隆400 mgbid可使卒中年发生风险从1.8%降至1.2%；治疗组缺血性卒中风险为年0.9%，两组年出血性卒中发生率相似（0.2%）。研究提示，在接受常规抗栓治疗前提下，决奈达隆可能会进一步减少房颤患者卒中发生风险。
最近Christiansen等(Christiansen CB, Torp-Pedersen C, Køber L. 2010)对既往7项有关决奈达隆研究（包括DAFNE、ADONIS、EURIDIS、ATHENA、ANDROMEDA、ERATO及DIONYSOS）回顾性分析发现，治疗组3439例患者中有54例（1.6%）发生卒中，对照组3048例患者中有76例(2.5%)发生卒中，并得出决奈达隆可减少房颤患者卒中发生的结论，其认为减少卒中的原因可能是与治疗组房颤的心室率减慢及血压降低（收缩压及舒张压均较对照组降低3mmHg）有关。
4. 相关心血管事件的临床分析Hohnlose等（Hohnloser SH, Crijns HJ, van Eickels M, et al. 2009）对ATHENA研究的心血管事件分析发现，决奈达隆明显降低具有危险因素房颤患者（合并以下一个危险因素：年龄＞70岁、高血压、糖尿病、中风病史或栓塞病史、左房大或左室射血分数＜40%）的心血管疾病住院或死亡风险，使心血管病首次住院率降低26%，心血管死亡率降低29%，心律失常或猝死风险降低45%，全因死亡降低16%。这一研究结果极大地提升了人们对决奈达隆的兴趣，尤其是作为抗心律失常药物，决奈达隆是目前唯一可以改善患者预后的药物。特别值得关注的是，这种改善预后的作用并不局限于成功转复并维持窦性心律的患者，对于房颤转复未成功的患者，其所具有的独特的抗交感活性、扩张血管等作用仍然起到了重要的改善预后的作用。也就是说，虽然决奈达隆是作为抗心律失常药物进入临床的，但是其作用已经超越了抗心律失常本身。
最近一项荟萃分析（包括ERATO、DAFNE、EURIDIS、ADNOIS和ATHENA研究，共6 157例患者）发现，决奈达隆对房颤、房扑患者心室率的控制及窦性心律的维持均有益，减少房颤和(或)房扑患者首次因心血管病因的住院时间、降低该类患者的死亡率、减少心血管事件及猝死（HohnloserS, Connolly S, Van Eickels M, et al.2009）。虽然有研究表明严重心衰患者服用决奈达隆增加早期死亡率（死亡可能与心衰恶化相关），但荟萃分析仍然提示决奈达隆可减少具有危险因素的房颤患者心血管死亡率及住院率。
关于决奈达隆是否会增加心衰患者心血管事件的风险仍存在争议。ANDROMEDA研究(Kober L,Torp-Pedersen C, McMurray JJ, et al.2008)对NYHA心功能分级III～IV级的627例患者进行随访发现，在平均治疗2个月时，决奈达隆组较安慰剂组死亡明显增加，并发现死亡与治疗期间心衰恶化加重有关，而进一步随访发现两组死亡率在随访6个月后并无统计学差别。因此，对于严重心力衰竭的患者目前不建议应用决奈达隆。进一步的风险仍需要更多的研究加以明确。
5. 心血管以外的副作用
决奈达隆心血管以外的不良反应主要包括胃肠道的副反应、皮疹、一过性肌酐增高等。DAFNE研究证明高剂量决奈达隆患者因腹泻、恶心、呕吐等不良反应停药明显高于400mg bid（600 mg，800 mg bid组因不良反应过早停药者分别为22.6%和7.6%；400 mgbid为3.9%）。
在ATHENA研究中(Connolly SJ, Crijns HJ,Torp-PedersenC, et al. 2009)，与安慰剂比较，400 mgbid决奈达隆组患者胃肠道不良反应、皮肤不良反应、血肌酐增加发生率均增高。
目前决奈达隆的所有研究均未见甲状腺、眼睛及肺脏的毒副作用，即使使用800 mg/d剂量(Touboul P, Brugada J, Capucci A, et al. 2003)也未出现甲状腺、眼睛以及肺脏损害的临床表现。
小结
决奈达隆是一种有效的治疗房扑/房颤的药物，由于“去碘化”而无甲状腺和肺毒性，成为抗心律失常治疗的一个新型的更安全有效的武器。更重要的是，通过ATHENA等研究提示，决奈达隆能够显著降低房颤/房扑患者的发病率和死亡率，明显改善预后，成为抗心律失常药物中惟一一个存在独立与抗心律失常以外作用使患者获益的药物，具有一定的里程碑意义。当然，ANDROMEDA研究提示决奈达隆增加严重心力衰竭患者的心血管事件风险，但荟萃分析表明决奈达隆可减少具有危险因素的房颤患者心血管死亡及住院风险，因而其对于心衰患者治疗的安全性和有效性（尤其是对各种器质性心脏病患者）需要更多和更细致的研究来明确。
Landmark ATHENA Study Findings With Multaq®(dronedarone) Show 24% Reduction in Cardiovascular Hospitalisation or Death in Patients With Atrial Fibrillation
Paris, France - May 15, 2008 /PRNewswire/—Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that findings from the landmark ATHENA study showed that Multaq® (dronedarone), a potential therapy for the treatment of patients with atrial fibrillation or atrial flutter, decreased the risk of cardiovascular hospitalisations or death from any cause by a statistically significant 24% (p=0.00000002), meeting the study's primary endpoint. The ATHENA results will be presented at the late breaking clinical trial session of Heart Rhythm 2008, the Heart Rhythm Society's 29th Annual Scientific Sessions in San Francisco, USA.
For the first time in twenty years of clinical drug trials in atrial fibrillation, an investigational medicine, Multaq®, showed a significant decrease in the risk of cardiovascular death by 30% (p=0.03) on top of standard therapy, including rate control and antithrombotic drugs, in patients with atrial fibrillation or atrial flutter. Multaq® also significantly decreased the risk of arrhythmic death by 45% (p=0.01) and there were numerically fewer deaths (16%) from any cause in the dronedarone group compared to placebo (p=0.17). First cardiovascular hospitalisation was reduced by 25% (p=0.000000009) in the dronedarone group.
"The ATHENA results have the potential to change the face of atrial fibrillation management. For atrial fibrillation patients, who together with their physicians struggle on a daily basis to manage the dramatic consequences of this complex disease, Multaq® carries hope for patients" said Marc Cluzel, sanofi-aventis Senior Vice President, R&D. "This milestone is indicative of sanofi-aventis' commitment to bringing innovative therapies to market, and of our ongoing commitment to provide patients, physicians and public health stakeholders with breakthrough medicines in those therapeutic areas where there are major healthcare needs and limited solutions".
Atrial fibrillation is a major cause of hospitalisation and mortality and affects about 2.5 million people in the United States, as well as 4.5 million people in the European Union and is emerging as a growing public health concern due to an aging population. Patients suffering from atrial fibrillation have twice the risk of death, an increased risk of stroke and cardiovascular complications, including congestive heart failure. Furthermore atrial fibrillation considerably impairs patients' lives, mainly because of their inability to perform normal daily activities due to complaints of palpitations, chest pain, dyspnoea, fatigue or light-headedness, without consideration of the cumbersome and sometime serious constraints imposed by current therapies of atrial fibrillation.
"In atrial fibrillation where treatment morbidity-mortality benefit still needed to be demonstrated, ATHENA is a unique trial using clinically relevant outcomes such as cardiovascular hospitalisation or death as the primary endpoint. In this regard, the trial has clearly achieved these safety and efficacy endpoints," said Dr Stefan H. Hohnloser, J.W. from the Goethe University, Division of Clinical Electrophysiology, Frankfurt, Germany, who served as co-principal investigator of the ATHENA study. "As a consequence, dronedarone is the first safe treatment for atrial fibrillation, which has been demonstrated to reduce cardiovascular hospitalisation or mortality in patients with AF" he added.
The most frequently reported adverse events of Multaq® vs. placebo in the ATHENA trial were gastro-intestinal effects (26% vs. 22%), skin disorders (10% vs. 8%, mainly rash) and increased blood creatinine (4.7% vs. 1%). The mechanism of blood creatinine increase (inhibition of creatinine secretion at the renal tubular level) is well defined. Compared to placebo, Multaq® showed a low risk of pro-arrhythmia and no excess of hospitalisations for congestive heart failure. There was a similar rate of study drug discontinuation between the 2 study groups.
"ATHENA is truly a landmark trial, that marks a paradigm change for the management of atrial fibrillation," said Dr Christopher Cannon, a Senior Investigator in the TIMI Study Group at Brigham and Women's Hospital, who was not involved in the study. "Atrial fibrillation is a very common disease, and our prior treatment options have been focused only on symptom relief and a hope to not do harm, which has been the problem with prior antiarrhythmic drugs. Now, with a highly significant reduction in death or hospitalisation, as well as a 45% reduction in arrhythmic death or 30% cardiovascular death, dronedarone may become a first line treatment of atrial fibrillation".
ATHENA, the largest double blind randomised study in patients with atrial fibrillation, was conducted in more than 550 sites in 37 countries and enrolled a total of 4,628 patients. The landmark ATHENA trial is the first morbidity-mortality study as part of the Multaq® phase III clinical development program, which also included five other multinational clinical studies, an initial study, ANDROMEDA, conducted in patients with severe congestive heart failure and a recent decompensation, and a total of 4 international studies in atrial fibrillation: EURIDIS/ADONIS, ERATO, and the ongoing DIONYSOS trial.
Based upon this new clinical data, sanofi-aventis plans to submit a registration dossier to the European Medicines Agency (EMEA), and a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) during the 3rd quarter of 2008.
About Atrial Fibrillation / Flutter
Atrial fibrillation is a major cause of hospitalisation and mortality and affects about 2.5 million people in the USA and 4.5 million people in the European Union. The Atrial Fibrillation Foundation expects the number of patients with AF to double in the next 20 years. Without appropriate management, atrial fibrillation can lead to serious complications, such as stroke and congestive heart failure.
AF is a condition in which the upper chambers of the heart beat in an uncoordinated and disorganised fashion, resulting in an irregular and fast heart rhythm (i.e. an irregular heartbeat). Atrial flutter is an abnormal fast heart rhythm that occurs in the atria of the heart. This rhythm occurs often in individuals with other heart conditions (e.g. pericarditis, coronary artery disease, and cardiomyopathy). Atrial flutter frequently degenerates to atrial fibrillation. However, it may persist for months to years.
When blood is not completely pumped out of the heart's chambers, it can pool and clot. If a blood clot forms in the atria, it can exit the heart and block an artery in the brain, resulting in a stroke. Consequently, about 15 percent of all strokes result from atrial fibrillation.
The most common symptoms of atrial fibrillation include palpitations (a rapid, irregular, "flopping" movement or pounding sensation in the chest or neck), shortness of breath, dizziness and feeling of heaviness, or constriction in the chest. The disorder may even be more common than diagnosed, as patients may experience atrial fibrillation episodes that either do not cause symptoms or are not documented during their visits to the doctor.
About the ATHENA Study
The landmark ATHENA study is a randomised, placebo controlled, international multi-center study that evaluated for the first time a treatment on top of standard background therapy for the management of patients with atrial fibrillation in reducing morbidity and mortality by preventing cardiovascular hospitalisations or death from any cause. The study included 4,628 patients, which make it the largest ever outcome study of an anti-arrhythmic treatment for atrial fibrillation.
The ATHENA study objectives were to show a potential benefit of Multaq® on the primary composite endpoint of all-cause mortality combined with cardiovascular hospitalisation as compared to placebo. The pre-specified secondary endpoints were death from any cause, cardiovascular death and hospitalisation for cardiovascular reasons. The pre-specified safety endpoint was the incidence of treatment emergent adverse events (time of observation for treatment emergent adverse events) including: all adverse events, serious adverse events, adverse events leading to study drug discontinuation.
The atrial fibrillation or atrial flutter patients studied were either 75 years of age or over (with or without cardiovascular risk factor) or were below 75 years of age with at least one additional cardiovascular risk factor (hypertension, diabetes, previous cerebrovascular event, left atrium size greater than 50 mm or left ventricular ejection fraction lower than 40 percent). Patients suffering from decompensated heart failure were excluded from the study. Patients were randomised to receive Multaq® 400 mg BID or placebo, with a maximum follow-up of 30 months.
The countries which enrolled patients included: Argentina, Australia, Austria, Belgium, Canada, Chile, China, Czech Republic, Finland, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Malaysia, Mexico, Morocco, New Zealand, Norway, Philippines, Poland, Portugal, Russia, South Africa, Singapore, South Korea, Spain, Sweden, Taiwan, Thailand, The Netherlands, Tunisia, Turkey, the UK, the US.
About Multaq® (dronedarone)
Dronedarone (brand name Multaq®) is an investigational new treatment for patients with atrial fibrillation, which has been discovered and developed by sanofi-aventis for the prevention and treatment of patients with atrial fibrillation or atrial flutter. Dronedarone is a multi-channel blocker that affects calcium, potassium and sodium channels and has anti-adrenergic properties. Dronedarone does not contain the iodine radical and did not show any evidence of thyroid or pulmonary toxicity in clinical trials.
About sanofi-aventis in Cardiology and Thrombosis
Sanofi-aventis' unmatched experience in the treatment of millions of patients suffering from cardiovascular disease (CVD) and thrombosis has uniquely prepared us to take on the growing challenges in these domains. Today, together with academic institutions and healthcare professionals, we are a major contributor in the effort to reduce the public health burden across the broad CVD spectrum and in thrombosis.
Our comprehensive set of innovative therapeutic solutions includes antiplatelet and antithrombotic agents with Plavix® and Clexane®/Lovenox®, as well the antihypertensive agent Aprovel®/Avapro®. By listening and responding to the needs of patients and physicians, we constantly seek to improve the safety and efficacy of our products while developing new therapeutic strategies. Our dedication has already helped lay the foundations of modern cardiovascular treatment. In addition to the first-in-class ticlopidine, we pioneered treatment with amiodarone and heparins, therapies rooted in a deep legacy of research experience spanning decades.
Building on our deep foundations of experience and expertise, we are seeking improved treatment efficacy with new ultra-low-weight heparins (AVE5026), with a new reversible, long-acting anticoagulant, potentially better-suited for venous thromboembolism and atrial fibrillation (biotinylated Idraparinux). Our research into atrial fibrillation continues with ground breaking trials like ATHENA with the clinical development of dronedarone (Multaq®). We are simultaneously exploring targeted gene therapy (NV1FGF) with the aim of reducing the risk of amputation in patients with critical ischemia of the lower limbs. As we continue to push the frontiers of cardiovascular and thrombosis therapy, we do so with the conviction that the health of patients is our total commitment and our greatest reward.
About sanofi-aventis
Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
Forward Looking Statements
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Contact Info
Salah Mahyaoui
+33 (0)6.73.68.78.88