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For the first time since statins have been regularly used, a large study has found that another type of cholesterol-lowering drug can protect people from heart attacks and strokes.
自从他汀类成为常规药物以来，专家首次在一项大规模研究中发现，另一种降胆固醇的药物，也可以预防心肌梗死和脑卒中。
The finding can help millions at high risk of heart attacks who cannot tolerate statins or do not respond to them sufficiently. And it helps clarify the role of LDL cholesterol, the dangerous form. Some had argued that statins reduced heart attack risk not just by lowering LDL levels but also by reducing inflammation. The new study indicates that the crucial factor is LDL, and the lower, the better.
无数患者可能会从该发现中受益。这些人心肌梗死的风险较高，但又不能耐受他汀，或者摄入他汀的效果不明显。这一发现还有助于研究者进一步认识危险的低密度脂蛋白(LDL)胆固醇的作用。一些人认为，他汀类药物之所以能减少心肌梗死的风险，是因为它不仅降低了LDL水平，而且还减少了炎症。而这项新的研究表明，LDL才是关键因素，并且它的水平越低越好。
The six year study, reported Monday at the annual meeting of the American Heart Association, involved 18,000 people who had had heart attacks or episodes of chest pain so severe they went to a hospital. They were randomly assigned to take a statin or a combination of a statin and the alternative drug to further reduce LDL levels. Both groups ended up with very low LDL levels – those taking the statin, simvastatin, had an average LDL of 69, and those taking simvastatin and the other drug, ezetimibe, or Zetia, in a combination pill sold as Vytorin, had an average LDL of 54. No clinical trial had ever asked what happened when LDL levels get below 70 because, said Dr. Robert Califf, a Duke cardiologist and the study chairman, "many people were nervous about going this low and imagined a lot of possible toxicities."
本周一，相关研究人员在美国心脏协会(American Heart Association)的年会上做了报告。这项研究耗时六年，涵盖1.8万名患者。他们均曾经历过心肌梗死，或者严重到需要到医院就诊的胸痛发作。研究人员随机向他们分配了他汀，或者他汀和替代药物组成的复方药，以便进一步降低他们的LDL水平。结果两组患者的LDL都减至非常低的水平——服用他汀类药物辛伐他汀的患者，LDL的平均水平为69，而服用复方药的患者，LDL的平均水平为54。该复方药的商品名为葆至能(Vytorin)，由辛伐他汀和依折麦布组成，而后者又称为艾泽庭(Zetia)。这项研究的主管、杜克大学的心脏病学家罗伯特·卡里夫(Robert Califf)博士说，之前没人通过临床试验来研究LDL水平低于70时会发生什么状况，因为“LDL降到这么低的水平令很多人感到紧张，觉得可能会产生很多坏处。”
Statins lower LDL by preventing it from being made. Ezetimibe lowers LDL by preventing cholesterol from being absorbed in the gut.
他汀降低LDL的方式是防止它生成，而依折麦布降低LDL的方式是防止肠道吸收胆固醇。
The drugs were so effective that there were few cardiac events among the participants but eventually a difference emerged: 6.4 percent fewer heart disease deaths, heart attacks, strokes, bypass surgery, stent insertion and severe chest pain leading to hospitalization in those assigned to take Vytorin. The amount corresponded to what was predicted from the extra degree of cholesterol lowering with the combination drug.
两种药物均非常有效，参与实验的患者出现心血管意外的次数不多，但差别最终浮现了出来：在心脏疾病死亡、心肌梗死、脑卒中、搭桥手术、支架置入和导致住院的严重胸痛方面，摄入葆至能的患者相对低6.4%。考虑到葆至能可以把胆固醇水平降得更低，据此预测的水平与以上实验数据相符。
Those results translate into 2,742 events in those taking simvastatin and 2,572 in those taking the combination drug. That means, said Dr. Christopher Cannon, a principal investigator and cardiologist at Brigham and Women’s Hospital, that two out of every 100 people who would have had a heart attack or stroke by taking the statin avoided those outcomes by taking the combination drug.
这些结果对应的数据是，服用辛伐他汀的患者中出现了2742次心血管意外，而服用葆至能的患者中有2572次。布莱根妇女医院(Brigham and Women’s Hospital)的首席研究员、心脏病学专家克里斯托弗·坎农(Christopher Cannon)博士说，这意味着，在100个服用了他汀但仍会心肌梗死或中风的患者，如果服用的是复方药，本来应该可以避免2例这种情况。
And, adds Dr. Califf, the study found absolutely no side effects from ezetimibe — no excess cancer, no muscle aches no headaches. “It looks like placebo,” he said.
卡里夫博士称，该研究还发现，依折麦布完全没有副作用——不会增加罹患癌症的风险，不会造成肌肉酸痛或头痛。“看上去就像安慰剂，”他说。
The study was sponsored by Merck, the maker of Vytorin, but the investigators had the right to publish what they wanted, with final say over what they wrote.
这项研究由葆至能的生产商默克公司(Merck)赞助，但研究人员有权按照自己的意愿来发布内容，对报告的撰写拥有最后决定权。
“Fantastic,” said Dr. Sekar Kathiresan of the Broad Institute and Massachusetts General Hospital who studies the genetics of heart disease but had no part in the study. “A truly spectacular result for patients.”
“这项研究太棒了，对于患者来说，这是一大福音，”在博德研究所(Broad Institute)和马萨诸塞州综合医院(Massachusetts General Hospital)研究心脏疾病基因的谢卡尔·卡斯瑞斯安(Sekar Kathiresan)博士说。他本人并未参与这项研究。
Dr. Harlan M. Krumholz, a Yale cardiologist not associated with the study, said he wished there was a peer-reviewed journal article instead of a presentation of the results at a meeting — the data analysis was completed just last week — but, assuming the result holds up, “this is the result we were hoping for.”
耶鲁大学心脏病学专家哈伦·M·克鲁姆霍尔茨(Harlan M. Krumholz)博士也没有参与该研究。他表示，希望这项成果以同行评议的期刊文章方式发表，而不是在会议上做演示——研究的数据分析上周刚刚完成——但是，假设这个结果经得起推敲，“这会是我们希望看到的结果。”
At the same time, and by sheer coincidence, two other groups of researchers reported genetic studies that supported the trial’s conclusions. One, led by Dr. Brian A. Ference of Wayne State University School of Medicine found that gene mutations mimicking the effect of ezetimibe and ones mimicking the effect of statins had the same effect on heart disease risk for a given reduction in cholesterol. The implication, he said, is that “lowering cholesterol with ezetimibe, or a statin, or both, should each lower the risk of heart disease by about the same amount.”
纯属巧合的是，另外两个研究团队也在同时发布了遗传学领域的成果，支持了该临床研究的结论。其中一个团队由韦恩州立大学(Wayne State University)医学院的布莱恩·A·费伦斯(Brian A. Ference)领导。他们发现，对于给定的胆固醇减少量，模仿依折麦布效果的基因突变，和模仿他汀效果的突变，对心脏疾病风险产生了相同的效果。这意味着，“用依折麦布降低胆固醇，或者用他汀，或两者都用，应该都可以同等程度地降低心脏疾病风险，”他说。
The other, led by Dr. Kathiresan, examined mutations that disabled one copy of the cholesterol absorption gene, producing the same effect as ezetimibe. The result was a 50 percent reduction in cholesterol absorption — the same as produced by ezetimibe — and an LDL reduction of 12 milligrams per deciliter of blood, also the same amount as produced by ezetimibe. The mutation, which gave people the equivalent of a lifelong exposure to ezetimibe, reduced the heart attack rate by 50 percent.
另外一个团队则在卡斯瑞斯安博士的领导下，研究了让一个胆固醇吸收基因拷贝无法发挥作用的突变，获得了和使用依折麦布相同的效果。他们的结论是，胆固醇吸收量减少了50%——与依折麦布效果相同——每100豪升血液的LDL降低了12毫克，也与依折麦布的效果相同。这个突变相当于终生摄入依折麦布，可让心肌梗死几率降低50%。
The study’s results are making many wonder about the latest cholesterol guidelines, which did not mention any drug other than a statin. And instead of providing goals for cholesterol levels, they simply advised those at high risk to take a statin. Period.
得知这项研究的结果后，很多人对最新的胆固醇指南产生了困惑。文中没有提及他汀之外的任何药物，也没有提供胆固醇水平的目标值，只是劝高风险人群摄入他汀。别无其他。
“The guidelines didn’t say they didn’t believe in cholesterol, but they made it clear that the evidence is for a statin, not for any agent that lowers cholesterol,” said Dr. Eugene Braunwald, a study chairman who is a cardiologist at Brigham and Women’s and a longtime leader in the field.
“指南没有说他们不相信胆固醇的作用，但他们明确表示，相关证据只涉及他汀，不涉及其他降胆固醇的药物，”该领域长期以来的领军人物尤金·布朗瓦德(Eugene Braunwald)博士说。他是一个研究会的主席，也是布莱根妇女医院的心脏病学专家。
Dr. Neil Stone, the head of the guidelines committee and a cardiologist at Northwestern University, has a more nuanced view of what the guidelines say, but adds that the study result “gives doctors another option if they have a patient who can’t tolerate a high-intensity statin.”
西北大学(Northwestern University)心脏病学专家尼尔·斯通(Neil Stone)博士是胆固醇指南委员会的主管。对于指南内容的含义，他认为比布朗瓦德的说法更为微妙。但他也表示，“如果遇到无法耐受大剂量他汀的患者”，这项研究结果“给医生提供了另一个选择”。
