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12月1日星期一（健康日报新闻）――尽管辉瑞公司新的调节胆固醇药物引起了死亡，研究者们说他们仍不会放弃通过升高“好”胆固醇来防治心脏疾病的探索。

近年来降低低密度脂蛋白胆固醇（LDL）即“坏”胆固醇，是心脏病学研究的主要焦点，然而升高其类似物高密度脂蛋白胆固醇（HDL），也具有很好的效果。事实上辉瑞打算将这个升高HDL的药物torcetrapib与降低LDL的药物立普妥一起上市，后者是目前世界上最畅销的他汀类药物。因参与临床试验的病人发生意料之外的死亡和心脏问题，torcetrapib上市被禁止。辉瑞，这个世界上最大的药物制造商，已经投入了8亿美元的资金。

迈阿密大学米勒医学院医学和生理学教授Robert Myerburg博士说：“已经有明确的证据证实除降低LDL外，升高HDL也能减少心脏事件发生率，这已经有足够的资料支持，（该药物的推出）也正是基于这个理论。纽约大学医学院临床副教授Daniel Fisher博士说：“这是一个合理的策略”。有专家说：虽然HDL在控制心脏病方面的重要性不如LDL，但它仍扮演重要角色。

作为美国心脏病协会发言人、位于佛罗里达Jacksonville的Mayo临床医学院的医学教授Gerald Fletcher说：“在防治心脏病方面被广泛重视的因素有6个，其中HDL是从来都没有被去掉的，它的重要性虽然不及LDL，但其作用仍然是很重要的。”

与torcetrapib类似的一些其他药物仍处在上市过程的不同阶段，但目前仍不清楚因torcetrapib引起的问题是否还会出现在这些药物中。Myerburg说：“我们不知道是因为这类药物的类效应还是药物之间的潜在影响。对服用多种药物的人来说，能提供多少额外的益处仍不清楚。”

此时，医生和病人已经开始选择Niaspan，它是一种烟酸的缓释剂型，但它的作用较torcetrapib逊色。Fisher说：“Niaspan也能升高HDL但作用较弱，它与torcetrapib不在同一水平上。Myerburg说：“因为Niaspan同时也降低LDL，所以很难判定产生有益作用的机制，我们不知道到底是升高HDL还是降低LDL在降低心脏事件中起了主要作用。”

Niaspan的作用机制完全与torcetrapib不同，它可以引起皮肤发红不适，容易导致病人停用这个药物。目前由政府支持的一项临床试验正判定其与他汀类合用的效果。

Fisher说：“氯贝特也可升高好胆固醇，但是它与他汀类合用时会产生令人讨厌的肌肉和肝脏的不良反应。”

他汀类药物也能升高HDL，但其作用较Niaspan和torcetrapib均小。Fletcher说：“也有不用服药其他的方法能升高HDL，那就是有规律的严格的运动，但是这需要日积月累长时间的效果。”

Raising 'Good' Cholesterol Levels Still a Worthy Goal
Despite death of Pfizer drug, researchers say investigation of concept should continue

HealthDay
Monday, December 11, 2006

MONDAY, Dec. 11 (HealthDay News) -- Despite the death of Pfizer's new cholesterol drug, researchers say they are not abandoning their quest to find ways to prevent heart disease by raising levels of "good" cholesterol.

Reducing LDL, or "bad" cholesterol, has been the main focus of cardiology in recent years, but boosting its counterpart, HDL, also has a salutary effect.

Indeed, Pfizer was intending to market the new drug with Lipitor, a cholesterol-lowering statin that happens to be the world's best-selling drug. But the development of the drug, torcetrapib, was hurriedly shut down on Dec. 2 because of an unexpected number of deaths and cardiovascular problems in patients participating in clinical trials. Pfizer, the world's largest drug maker, had already poured $800 million into the venture.

Increasing HDL lowers event rates, while lowering LDL cholesterol does the same, explained Dr. Robert Myerburg, a professor of medicine and physiology at the University of Miami's Miller School of Medicine. "That's pretty well-established. There's good supporting data, and the rationale is there."

"It's a valid strategy," added Dr. Daniel Fisher, a clinical assistant professor of medicine at New York University School of Medicine in New York City.

While HDL is not as important as LDL in controlling heart disease, it's still a player, experts say.

"There are six major factors that we've designated that are vastly important in the prevention and control of heart disease, and HDL has never made that cut," explained Dr. Gerald Fletcher, a spokesman for the American Heart Association and a professor of medicine at the Mayo Clinic College of Medicine, in Jacksonville, Fla. "HDL has never been established as that important compared to LDL, but it's certainly important."

Other drugs that are similar to torcetrapib are currently in various stages of development, but it's not clear if the problems that cropped up with torcetrapib will reappear with those medications.

"We don't know the class effect or the potency of the drugs," Myerburg stated. "And we don't know how much added benefit they will provide to the person taking multiple drugs."

In the meantime, doctors and patients already have Niaspan, an extended-release version of niacin. Niaspan is less potent than torcetrapib.

"Niaspan also raises HDL but to a lesser extent," Fisher said. "It's not even in the same ballpark."

And because Niaspan also lowers LDL, it's hard to tease out what's causing the good. "Which is a major player in improving event rates?" Myerburg asked. "We don't know where the benefit is coming from."

And Niaspan, which works by a completely different mechanism than torcetrapib, causes uncomfortable skin flushing that can prompt some patients to discontinue taking their medication. A government-sponsored trial is currently looking at how Niaspan works in combination with statins.

Drugs called fibrates can also boost good cholesterol but, in combination with statins, can have undesirable muscle and liver effects, Fisher said.

Statins themselves raise HDL as well, but to a much lesser extent than either Niaspan or torcetrapib.

There are other things patients can do that don't involve taking another pill, experts added.

"A regular, dedicated exercise program will elevate HDL, but it has to be a long-term thing," Fletcher said.

http://www.nlm.nih.gov/medlineplus/news/fullstory_42459.html

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