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[ACC2010]对于他汀类与贝特类降脂药物联合应用比单用他汀类药物效果如何--Marshall Elam教授专访

作者:国际循环网   日期:2010/3/16 17:23:00

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《国际循环》:联合降脂治疗时,如果出现肝功能损害,您是首选停用他汀类药物还是贝特类药物?

  《国际循环》:在ACCORD研究中,对于糖尿病患者来说,他汀类与贝特类降脂药物联合应用比单用他汀类药物效果如何?

    Elam教授:你的问题是他汀与贝特类药物联合治疗与他汀类药物单药治疗相比的疗效。这就是ACCORD血脂试验设计的主要假设。也就是对于2型糖尿病患者,我们知道,首先2型糖尿病患者发生心血管事件的风险很高,我们同时也知道应用了他汀类药物的研究中,2型糖尿病患者发生心血管疾病的风险降低。我们知道观察贝特类药物的研究提示其同样能够降低心血管风险。但是,患者仍然存在较高的剩留风险。因此,在ACCORD血脂研究中,我们观察了联合治疗的疗效,即应用他汀来降低LDL-C,同时联用贝特类药物——ACCORD血脂试验中应用的是非诺贝特,来升高HDL-C和甘油三酯,该试验首次观察了他汀与贝特类药物联合治疗与他汀类药物单药治疗相比能否降低心血管事件发生的风险。ACCORD试验总体上带给我们的信息就是,总体上联合治疗不能够降低心血管事件发生的风险。我们在亚组分析中发现,高甘油三酯和低HDL-C的患者(在ACCORD血脂试验中是TG> 204mg/dl和HDL-C <34mg/dl)应用联合治疗能够获得某些心血管益处。这一特别的发现在以往的贝特类药物的试验中也观察得到,包括赫尔辛基心脏研究、BIP试验和FIELD试验。在这一亚组患者中,FIELD试验中观察的是糖尿病患者,贝特类药物能够在某种程度上降低心血管风险。因此,我想从ACCORD血脂研究和其他贝特类的研究中,我们可以发现,糖尿病患者应用他汀类药物治疗后TG水平高和HDL-C水平低时,应当考虑联用贝特类药物或者其他能够降低TG、升高HDL-C的药物。

   <International circulation>:In the ACCORD trial,compared with the using singly Statin, what is the  difference between combination of Fibtates and Statin in diabete?

   Dr Elam KEN:So the question is using combination therapy versus statin mono-therapy, and that actually is the key premise that the ACCORD study was based on. And that is, in patients with type two diabetes, we know that firstly, they are at very high risk of cardiovascular events. We also know that studies that have used statins, lower cardiovascular risk in those patients. We know that studies using fibrates by themselves also lower cardiovascular risk. But the risk remains high. So that is what led us in the ACCORD study to examine the impact of combination therapy, using the statin to lower LDL cholesterol and then adding a fibrate, fenofibrate in this case, to raise HDL and lower triglycerides, and to test what has never been tested before, and that is, does it really impact cardiovascular events? And the overall message, in the ACCORD study cohort, was that we did not see an overall impact on cardiovascular events by using combination therapy. What we did find in subset analysis is that the patients who came into the trial, who had high triglycerides and low HDL (in this case it was a triglyceride level greater than 204mg/dl and an HDL of less than 34mg/dl), in that subset of patients there was a suggestion that they may well have seen some benefit. This particular observation has actually been made now in several of the fibrate trials, including the Helsinki Heart Study, the Bezafibrate Infarction Prevention trial and the more recent FIELD study, that when you look at this subgroup of patients, and in the case of the FIELD study it was diabetics, that fibrates do appear to confer some risk reduction. So I think the message from this study and these studies, is that if you treat a patient with statin, in this case a diabetic, and after that, after statin therapy, the triglycerides remain high and the HDL remain low, then you should consider adding a second agent, a fibrate, or some other agent to address the triglyceride and HDL. 

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