对狼医回复的回复：关于心脏病，他汀的讨论

狼医生的帖子在这里：回Lily168：关于心脏病的几组数据。

http://bbs.wenxuecity.com/health/550488.html

我的回复:

狼医专门为我写了回贴，我很感激，这肯定是为了帮助我渐进式地接近真相。

先回应您最后的那句话。我的原话是“我同意这个原作者，不见得是出于他个人利益在这么说，他不过是产业链里最下面那个成员。” 这如何变成了 “每一个医生都在谋财害命”。。。喔喔喔，我可但当不起哦。我当时其实是还有半句没说出来的: “不过是产业链里最下面那个成员，要分也分不到半杯羹”。但是既然是我偷懒省去了，话没说全，冒犯了医生，也不能怪您生气。所以先解释一下。

 

1。两张图

首先要问的是：什么导致了那个持续上升的肥胖率？这个现象后面的本质是啥?

当然有很多说法。我现在唯一要点到的是：同一时期大力提倡普及的饮食指南是食物金字塔。

 

减少吸烟，降血压，降血脂：它们各自的影响力是多少呢？

按照WHO Monica调查分析，导致心血管疾病的主要因素是吸烟而不是高胆固醇，80%的心血管疾病由吸烟、缺乏运动、不健康饮食、不健康生活方式造成。所以当吸烟大大减少时，死亡率下降是可以预期的。Framingham的调查也显示，运动量最多的那部分人的死亡率低于运动量最低的那部分人40%

高血压降下来的作用也是减少死亡率的原因，对这个没有异议。

这两条曲线我觉得可能体现了因果关系。

 

至于血脂呢，这些年它下降的趋势肯定是不用看任何资料就知道的。因为他汀普及覆盖面那么大，米国人只要有保险和家庭医生做体检的，一旦血脂偏高，一定被他汀，跑不掉的。而这些药能确实有效地降血脂。我还可以预测，将来它还会更走低。

 

问题是：降下来的血脂，到底对死亡率的下降有多大的影响呢？这个图表上当然看不出来。要去看那些临床试验数据。

 

那么导致CHD死亡率下降的还有没有其他的因素？

溶栓药物

手术， angioplasty等

急救技术上的飞跃发展

这些是否有贡献？

 

2。扯蛋砖家是谁？我去搜了下，原来是个英国人。这个扯蛋说法后面的实质是个重要的问题：他汀作为一度预防的使用范围应该多广，该如何来决定？

 

Dr John Reckless, chairman of Heart UK and a consultant endocrinologist at Bath University

 

Increasingly, doctors are suggesting statins should be given to people with risk factors but

no obvious disease, which is called primary prevention. This is to prevent disease occurring in the first place.

 

But is the threat of cardiovascular disease so great that statins may as well be added to the water supply?

 

This was the debate held recently by doctors at the annual meeting of Heart UK - a patient and science charity for cholesterol.

Mass treatment

Dr John Reckless, chairman of Heart UK and a consultant endocrinologist at Bath University, put forward the case.  http://news.bbc.co.uk/2/hi/health/3931157.stm

 

3 和4。他汀多有效？是否副作用少？

 

这个问题要掰开讲的话就得翻那些实验文献了。对我来说很难，很花时间。我不知道你指的那些著名实验具体是那些。我对他汀的疗效还没有系统去了解过，我所粗率知道的是WOSCOPS，AFCAPS/TexCAPS，4S，ENHANCE，LIPID，CARE，ALLHAT，PROSPER，Heart Protection Study，ProveIt，JUPITER。我主要关注的数据是absolute risk的减少，而不是relative risk，还有那个NNT数字。

举个例子吧：如果看下面这5个实验，PROSPER,

ALLHAT-LLT, ASCOT-LLA, AFCAPS and WOSCOPS, statin drugs provided an Absolute 

Risk Reduction in total mortality of 0.3%.

您若是推荐具体的实验文献，我肯定是会找时间去看的。看不看得出门道来也难说，只能是去慢慢地学罢了。

 

他汀的副作用：我以前知道的是肌肉痛，性欲减低等这些普遍的副作用。

还知道那个吃Lipitor吃得完全失忆的NASA宇航员医生，写了“Lipitor Thief of Memory”这本书的作者Duane Graveline。

 

但是最近看到的是一些以前不知道的副作用，如糖尿病（他汀导致胰岛素抗拒，血糖升高）

 

这算是个综述：

The Ugly Side of Statins. Systemic Appraisal of the Contemporary Un-Known Unknowns

http://file.scirp.org/Html/3-1980073_34065.htm

(这篇文章里引用的那些研究我还没去查过对照过。)

 

还有这个他汀与癌症的动物实验:

Carcinogenicity of Lipid-Lowering Drugs

Data Synthesis. —All members of the two most popular classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in rodents, in some cases at levels of animal exposure close to those prescribed to humans. In contrast, few of the antihypertensive drugs have been found to be carcinogenic in rodents. Evidence of carcinogenicity of lipid-lowering drugs from clinical trials in humans is inconclusive because of inconsistent results and insufficient duration of follow-up.

 

Conclusions. —Extrapolation of this evidence of carcinogenesis from rodents to humans is an uncertain process. Longer-termclinical trials and careful postmarketing surveillance during the next several decades are needed to determine whether cholesterol-lowering drugs cause cancer in humans. In the meantime, the results of experiments in animals and humans

suggest that lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease.(JAMA. 1996;275:55-60)

 http://jama.jamanetwork.com/article.aspx?articleid=393579

 

对是否贴这个文献我犹豫了很久。最终贴出来，是觉得：癌症形成过程挺长，而他汀临床试验期一般不会超过5年。至于大量病人常年吃他汀，随着年龄越来越老，若是有癌症出现，要厘清它与他汀到底有何关系是不那么轻易的。这属于我所说的：真相未知。对于没有心脏病但血脂高的那个群体，我觉得这种研究在决定是否吃药预防心血管病时是应该拿来做个参考的。

 

另外贴一个对新的NCEP胆固醇治疗新指南所依赖的那些实验数据的分析

Analysis

Should people at low risk of cardiovascular disease take a statin?

BMJ 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f6123 (Published 22 October 2013)

http://www.bmj.com/content/347/bmj.f6123

 

 

5。医生／专家与药厂的关系，我只想举下面这个例子，其他的不想拿出来多说，免得被人误解成我对医学／科学持仇视态度。我若是不相信科学，不会去花这么多时间寻找原始资料来自学。但是我不迷信科学：医生科学家是人不是神。

 

对您，和坛子里其他的医生科学家们我是尊敬的。很欣赏你们对坛友许多问题的耐心解答。

 

 

写2001 NCEP胆固醇指南的委员会里的专家们：

Scott M.Grundy, MD, PhD (Chair of the panel), Diane Becker, RN, MPH, ScD, Luther T.

Clark, MD, Richard S. Cooper, MD, Margo A. Denke, MD, Wm. James Howard, MD,

Donald B. Hunninghake, MD, D. Roger Illingworth, MD, PhD, Russell V. Luepker,

MD, MS, Patrick McBride, MD, MPH, James M. McKenney, PharmD, Richard C.

Pasternak, MD, Neil J. Stone, MD, Linda Van Horn, PhD, RD

 

他们的 financial disclosure:

Dr Grundy has received honoraria from Merck, Pfizer, Sankyo, Bayer, and Bristol-Myers

Squibb. Dr Hunninghake has current grants from Merck, Pfizer, Kos

Pharmaceuticals, Schering Plough, Wyeth Ayerst, Sankyo, Bayer, AstraZeneca,

Bristol-Myers Squibb, and G. D. Searle; he has also received consulting

honoraria from Merck, Pfizer, Kos Pharmaceuticals, Sankyo, AstraZeneca, and

Bayer. Dr McBride has received grants and/or research support from Pfizer,

Merck, Parke-Davis, and AstraZeneca; has served as a consultant for Kos

Pharmaceuticals, Abbott, and Merck; and has received honoraria from Abbott,

Bristol-Myers Squibb, Novartis, Merck, Kos Pharmaceuticals, Parke-Davis,

Pfizer, and DuPont. Dr Pasternak has served as a consultant for and received

honoraria from Merck, Pfizer, and Kos Pharmaceuticals, and has received grants

from Merck and Pfizer. Dr Stone has served as a consultant and/or received

honoraria for lectures from Abbott, Bayer, Bristol-Myers Squibb, Kos

Pharmaceuticals, Merck, Novartis, Parke-Davis/Pfizer, and Sankyo. Dr Schwartz

has served as a consultant for and/or conducted research funded by

Bristol-Myers Squibb, AstraZeneca, Merck, Johnson & Johnson-Merck, and

Pfizer.

 

目前我的认识是：他汀对二度预防是有效果的。所以不能说他汀是毒药；但即使在二度预防上，它也不是仙丹。这是否接近真相，有待时间证实，也期待新资料的修正。