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[AHA2008] 《国际循环》顾问委员Peter Kowey教授访谈-心律失常的药物治疗
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 编辑:国际循环网 时间:2008/11/13 18:09:00 关键字:心律失常 决奈达隆 ATHENA研究 Peter Kowey 


Peter Kowey教授
美国托马斯杰弗逊大学杰弗逊医学院临床药理学教授,Main Line医学中心心血管医学部主任。
 

International Circulation: Pharmacologic antiarrythmic therapy is the most commonly used treatment in most patients with atrial fibrillation (AF), but currently available agents are limited by risks that may offset the benefits of sinus rhythm. In your opinion, where should the focus be in developing antiarrythmic agents? Which kinds of agents could block multiple ion channels simultaneously?
《国际循环》:抗心律失常药物常用来治疗房颤而对于维持窦性心律作用有限。您认为抗心律失常药物发展的重点是什么?哪些药物可对于多种离子通道同时有作用?

 

Professor Kowey: You are correct that we have limited pharmacologic options and it is a major problem in clinical practice. We have many patients who need to be treated to reduce their symptoms and don’t necessarily want to undergo catheter or surgical procedures for this. There are a number of drugs that are in clinical development, some of which have the property of being multiple ion channel blockers. The promise is that these drugs will effective because of their multi-channel effects, much as amiodarone is effective. Amiodarone is, of course, the most effective drug we have for this indication but it is limited because of its toxicity. We are hopeful that drugs such as dronedarone and vernakalant, which have multiple ion channel blocking properties, will be successful in clinical development. We still have some time to wait to see if that happens.
Kowey教授:在抗心律失常治疗时我们能选择的药物很有限,这是临床工作中的一个大问题。许多患者需要进行治疗来改善症状,但他们不一定想要进行导管或外科手术治疗。许多具有多离子通道阻滞剂特性的药物正在进行临床研究。它们的多通道作用使其像胺碘酮一样有效。胺碘酮是目前治疗心律失常最有效的药物,但其毒性作用限制了它的应用。我们希望多离子通道阻滞剂,如决奈达隆和vernakalant,在不久的将来能够应用于临床。


 International Circulation: Dronedarone is designed for the treatment of atrial fibrillation and atrial flutter. What do you think of the safety and efficacy of dronedarone?
《国际循环》:您曾在文章中提到决奈达隆是4类可以同时阻断多个离子通道的药物之一。我们知道它是一类用于治疗心房颤动和心房扑动的药物。您认为其疗效和安全性如何?

 

Professor Kowey: I think that the efficacy has been well demonstrated in placebo controlled trials. I think that the safety has been well demonstrated for a very typical patient population in ATHENA. ATHENA studied patients who are very similar to the vast majority of patients who we treat for atrial fibrillation. In that study, the drug was not only safe but it appeared to have other benefits, including reduction of hospitalization and reduction of cardiovascular mortality. So I don’t think there is any question that the drug is effective and it is safe for that population. There are two caveats. One is that we don’t yet have a comparator study of dronedarone vs. other drugs like amiodarone, so talking about comparative efficacy is very difficult at this point. The second caveat is that we have some evidence that in severe heart failure the drug may have a liability and therefore won’t be applicable to a group of patients with severe heart failure.
Kowey教授:在安慰剂对照试验中其疗效已被证实。在ATHENA研究的患者中,其安全性也有很好体现。ATHENA研究的患者与大多数行心房颤动治疗的患者相似。这项研究不仅证实了药物的安全性,也发现了其他益处,如降低住院率和心血管死亡率,因此我认为决奈达隆治疗心房颤动患者是有效而安全的。有两点需要注意:一是我们还没有决奈达隆和其他药物如胺碘酮的对照研究,因此在这一点上讨论决奈达隆的相对有效性非常困难;二是我们有一些证据表明决奈达隆可能不适用于严重心力衰竭患者。

 

International Circulation: Do you know of any plans for a comparative study like you mentioned?
《国际循环》:您有任何像您提到的对比研究计划吗?

 

Professor Kowey: There is a study called DIONYSOS (Efficacy & Safety of Dronedarone Versus Amiodarone for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation), which is currently in progress in Europe, comparing amiodarone with dronedarone. I don’t have great detail about that trial. I am not involved in it at all, but I think that the information from that trial will begin to be able to sort out the relative efficacy.
Kowey教授:有一项DIONYSOS(决奈达隆和胺碘酮对于心房颤动患者维持窦性心律的有效性和安全性)研究正在欧洲进行。我不知道此试验的很多细节。我没有参与其中,但我认为试验中的信息会得到相对的有效性结果。

 

International Circulation: The choice of pharmacologic therapy for atrial fibrillation depends on whether or not the goal of treatment is to maintain sinus rhythm or to tolerate atrial fibrillation with adequate control of ventricular rate. I know some drugs that target remodeling and inflammation are being tested for their use in prevention of AF. Would you like to share with us some research progress of these new drugs?
《国际循环》:心房颤动的药物治疗取决于治疗的目标是维持窦性心律或控制心室率。我知道一些针对心脏重构和炎症方面的药物正在进行临床研究用以防治心房颤动。您可否介绍这方面一些新的药物?

 

Professor Kowey: There clearly is an initiative to find drugs to treat patients who have had atrial fibrillation—so called secondary prevention. The big question is, are we going to be able to come up with strategies to prevent the arrhythmia altogether—primary prevention. The answer is that we are hopeful. There are some preliminary data from other trials, trials conducted for non-AF purposes that suggest things like RAAS modulators like ACEIs and ARBs may be useful for that purpose. People are interested in anti-inflammatories, fish oils, statins, and pipar modulators. There are all kinds of candidates for this and there is great hope that some of these drugs will be helpful. What we need obviously are prospective randomized trials in at-risk populations to prove that these drugs do what they are intended to do before anybody can make recommendations about using them. Having said that, I think at this point in time, those of us in clinical practice, if we have a choice, for example in treating hypertension if we have a choice among drugs, we are much more likely to gravitate to drugs that have some potential at least to treat atrial fibrillation because it is the great problem in people with hypertensive heart disease. There are more data to collect but it is certainly very interesting so far.
Kowey教授:我们在寻找药物治疗心房颤动患者——即所谓的二级预防方面做了大量工作。现在的问题是,我们是否能够想出方法来阻止心律失常发生——即一级预防,我认为这方面的工<

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