Why did a promising heart drug fail? Doomed drug highlights complications of meddling with cholesterol. 1. The failure of a high-profile cholesterol drug has thrown a spotlight on the complicated machinery that regulates cholesterol levels. But many researchers remain confident that drugs to boost levels of good cholesterol are still one of the most promising means to combat spiralling heart disease. 2. Drug company Pfizer announced on 2 December that it was cancelling all clinical trials of torcetrapib, a drug designed to raise heart-protective high-density lipoproteins (HDLs). In a trial of 15000 patients, a safety board found that more people died or suffered cardiovascular problems after taking the drug plus a cholesterol-lowering statin than those in a control group who took the statin alone. 3. The news came as a kick in the teeth to many cardiologists because earlier tests in animals and people suggested it would lower rates of cardiovascular disease. There have been no red flags to my knowledge, says John Chapman, a specialist in lipoproteins and atherosclerosis at the National Institute for Health and Medical Research (INSERM) in Paris who has also studied torcetrapib. This cancellation came as a complete shock. 4. Torcetrapib is one of the most advanced of a new breed of drugs designed to raise levels of HDLs, which ferry cholesterol out of artery-clogging plaques to the liver for removal from the body. Specifically, torcetrapib blocks a protein called cholesterol ester transfer protein (CETP), which normally transfers the cholesterol from high-density lipoproteins to low density, plaque-promoting ones. Statins, in contrast, mainly work by lowering the bad low-density lipoproteins. Under pressure 5. Researchers are now trying to work out why and how the drug backfired, something that will not become clear until the clinical details are released by Pfizer. One hint lies in evidence from earlier trials that it slightly raises blood pressure in some patients. It was thought that this mild problem would be offset by the heart benefits of the drug. But it is possible that it actually proved fatal in some patients who already suffered high blood pressure. If blood pressure is the explanation, it would actually be good news for drug developers because it suggests that the problems are specific to this compound. Other prototype drugs that are being developed to block CETP work in a slightly different way and might not suffer the same downfall. 6. But it is also possible that the whole idea of blocking CETP is flawed, says Moti Kashyap, who directs atherosclerosis research at the VA Medical Center in Long Beach, California. When HDLs excrete cholesterol in the liver, they actually rely on LDLs for part of this process. So inhibiting CETP, which prevents the transfer of cholesterol from HDL to LDL, might actually cause an abnormal and irreversible accumulation of cholesterol in the body. Youre blocking a physiologic mechanism to eliminate cholesterol and effectively constipating the pathway, says Kashyap. Going up
GRE数学2014三大难点举例分析
gre数学知识点大盘点
gre数学策略:代入检验和界定范围
新GRE数学备考:圆的15道练习题
GRE数学:数据解释题重点试题(二)
gre数学 算术重点试题4
名师指导新GRE数学 数理统计
新GRE数学备考:画图法
十道不得不看的GRE数学经典排列组合题
GRE数学大全:基本概念总结篇
GRE数学备考中常见的15道难题
gre数学 算术重点试题1
新GRE数学要点解析:交集和并集
GRE考试中数学部分术语总汇
新gre数学排列组合例题解析
9.1—9.8机考题汇总(逻辑)
新GRE数学复习要点:交集和并集
备考辅导:新GRE数学要点指导
GRE数学数据解释题型的典型试题
新GRE数学概率分析
新GRE考试备考:数学词汇(8)
20道GRE数学难题复习
新GRE数学考试策略(一)
新gre数学考试策略(二)
GRE数学精华题型解析
GRE数学必看易错题
[GRE数学]GRE主要数学符号的英文表达
新gre数学词汇A-B
新GRE数学末重要考点指导
新GRE数学样题解析
| 不限 |
| 英语教案 |
| 英语课件 |
| 英语试题 |
| 不限 |
| 不限 |
| 上册 |
| 下册 |
| 不限 |