资讯内容 Content

[ACC2015]PCSK9抑制剂或提供血脂管理新选择——Iowa大学Jennifer Robinson教授专访

作者:J.Robinson 编辑:国际循环网 时间:2015/3/26 15:51:28    加入收藏

 标签:  关键字:PCSK9抑制剂 血脂管理 Jennifer Robinson 

  International Circulation: Are we entering a new phase of treatment with the PCSK9 inhibitors?

  Dr Robinson: We are all quite excited about this new class of drugs, PCSK9 monoclonal antibodies. We block PCSK9, which means that LDL receptors continue functioning and taking cholesterol out of the circulation. Normally, PCSK9 breaks down these LDL receptors thus preventing the removal of LDL. It lowers LDL-cholesterol a further 60-65% on top of background statin therapy. So these are very powerful drugs. What this opens our minds to is that we know statins are very effective and we know they cut the risk of heart attack, stroke and death by 30-50%, but that means there are still a lot of people having heart attacks and strokes and dying while using statins. So if we can cut that another 50%, that would be exciting. The reason I say 50% is because now we have two trials ongoing, one of which I had published today in the New England Journal of Medicine and another I am involved in and reported on here with evolocumab showing very similar results with one year of follow-up. Both studies were performed for safety but we found that in both trials, there was about a 50% reduction in heart attacks, strokes and cardiovascular deaths within a year to a year-and-a-half of treatment. That was evident almost immediately after people started taking the drug. It certainly looks like we lower LDL a lot, but we also have the potential to reduce cardiovascular events dramatically as well. That is why we are all pretty excited about this new class of drugs.

  International Circulation: So how do you see the next decade in lipid altering therapy?

  Dr Robinson: There are two PCSK9 inhibitors, alirocumab and evolocumab, which have been filed for approval with the USFDA and we hope they will receive that approval which will allow them to be used for LDL-lowering. That is a huge unmet need in terms of people with familial (genetic) hypercholesterolemia and also people who are statin intolerant or at least intolerant to the dose that they should take. This will give them another option to prevent future heart attacks and stroke. In the long-term, we will wait for the results of the cardiovascular outcomes trials which are ongoing with these drugs. These are high-risk patients with cardiovascular disease and on maximum statin therapy, to whom we add alirocumab (about 18000 people with acute coronary syndromes) or evolocumab (27000 people) and see if these PSCK9 inhibitors on top of statins will further reduce the risk for cardiovascular events. If they do, that’s exciting. There has been some pushback because they are monoclonal antibodies which is quite high tech, but I think if we can have something that can cut the risk for heart attack and stroke so dramatically, it will be very important to get that to our patients.




  International Circulation: Could you talk about the management strategy for LDL-cholesterol levels <25mg/dl or <15 mg/dl?

  Dr Robinson: We have looked at the pooled data from the alirocumab program and I reported on that here at the meeting. When you lower LDL another 65% on top of statins, you have a large number of people with LDL <25 and as low as 15, but there seem to be no signals there. There is no increase in adverse events at these very low LDL levels in the studies to-date. The long-term trials we are doing will give us a better feel for that, but there seems to be no increase in associated adverse events.

  《国际循环》:您能否谈谈对LDL-C水平<25mg/dl or <15 mg/dl的管理策略?

  Robinson教授:本次会议报道的来自alirocumab项目的汇总数据显示,在他汀类药物基础上将LDL再降低65%,则会有很多患者LDL<25 mg/dl,甚至低至15 mg/dl,但似乎没有任何征象出现。在该研究中这些非常低的LDL水平上,并无不良事件的增加。我们正在做的长期试验会让我们对此有更好的认识,但是相关不良事件似乎没有增加。

  International Circulation: Now you have reported on the trial results for PCSK9 thus far, should we be expecting a revision of the guidelines?

  Dr Robinson: The 2013 ACC/AHA Guidelines came out a year-and-a-half ago and changed the paradigm to maximizing statin therapy. We didn’t have any evidence for lower targets so they were not made recommendations. We just have evidence from IMPROVE-IT that adding ezetimibe gets LDL down by 20% and also modestly reduces cardiovascular events by 10%, so we have another drug we can add to statins for people who need more LDL-lowering. The guidelines state that they would prefer people to use non-statins only if they have been shown to reduce cardiovascular events because we had a string of trials with drugs that lowered LDL but didn’t reduce cardiovascular events. So that is the standard that is required. The fact that the preliminary studies suggest that there is cardiovascular risk reduction benefit with the PCSK9 inhibitors reassures us all that these drugs are going to do what we want them to do, which is to prevent heart attack and stroke.


  Robinson 教授:1年半前,2013年ACC/ AHA指南发布,使治疗模式变为最大化他汀类药物治疗。我们没有任何更低目标的证据,因此未做出推荐。我们只有来自IMPROVE-IT的证据,即添加依折麦布使LDL降低了20%,也使心血管事件小幅降低10%,现在对那些需要LDL降低更多的患者,我们有了另一种可以在他汀类药物基础上应用的药物。鉴于既往一系列试验显示,非他汀类药物降低LDL但并不减少心血管事件,因此指南指出,除非证明非他汀类药物可降低心血管事件,否则不推荐患者优选非他汀类药物。初步研究提示,PCSK9抑制剂有降低心血管疾病风险的益处,这令人欣慰,也正是我们想要的效果,即预防心脏并发作和卒中。



关于本站 | 设为首页 | 加入收藏 | 站长邮箱 | 友情链接 | 版权申明

声明:国际循环网( www.icirculation.com)对刊载的所有文章、视频、幻灯、音频等资源拥有全部版权。未经本站许可,不得转载。

国际循环 版权所有  2008-2020 icirculation.com  All Rights Reserved