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.
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