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 7.Most researchers remain confident that elevating high density lipoproteins levels by one means or another is one of the best routes for helping heart disease patients. But HDLs are complex and not entirely understood. One approved drug, called niacin, is known to both raise HDL and reduce cardiovascular risk but also causes an unpleasant sensation of heat and tingling. Researchers are exploring whether they can bypass this side effect and whether niacin can lower disease risk more than statins alone. Scientists are also working on several other means to bump up high-density lipoproteins by, for example, introducing synthetic HDLs. The only thing we know is dead in the water is torcetrapib, not the whole idea of raising HDL, says Michael Miller, director of preventive cardiology at the University of Maryland Medical Center, Baltimore.
SAT阅读题Sentence Completion Test 6
SAT阅读高分攻略系列(六)
SAT阅读高分攻略系列(八):文艺类阅读3
SAT阅读考试三大误区
SAT阅读题中的修辞手段题
2010年6月SAT阅读真题
SAT阅读完成句子试题9
SAT考试阅读练习题5
教你SAT阅读如何突破740
SAT阅读考试不再难,破解生词有方法
SAT阅读练习(三):SAT Sentence Completion 3
SAT阅读高分攻略系列(三)
SAT阅读题Sentence Completion第四套
SAT阅读考试答题方法全攻略
SAT阅读高分攻略系列(八):文艺类阅读2
SAT阅读高分攻略系列(八):文艺类阅读1
SAT阅读逻辑题解析
SAT阅读准备过程中可能遇到的问题
SAT阅读&写作必备英文小说推荐
如何有效备考SAT阅读理解
SAT考试阅读题型解析
SAT阅读考试常见题型分析
SAT阅读特点与备考策略讲解
SAT阅读完成句子试题6 含中文注释
SAT阅读考试应对策略
SAT阅读题型介绍与例题讲解
SAT阅读讲解:文章的分类
SAT阅读完成句子练习题(十)
SAT阅读高分攻略系列(七)
SAT阅读技巧讲解
不限 |
英语教案 |
英语课件 |
英语试题 |
不限 |
不限 |
上册 |
下册 |
不限 |