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  1. Richard Lehman, MRCGP, MA
  1. Department of Primary Care, University of Oxford
 Oxford, UK

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 Before the coming of standardised European road signs, roads that led nowhere in England used to be marked “No Through Road” or “Cul-de-Sac,” if they were marked at all. Unfortunately, there is no similar system to guide interventional trials of cardiovascular prevention. When researchers repeatedly go up a certain promising path and end up getting nowhere, others often still follow. Raising high density lipid cholesterol (HDL-C) is an example: observational data show that high levels are associated with fewer adverse cardiovascular outcomes, but no trial seems to arrive at that destination. Earlier trials used fibrates, but the latest have used new classes of HDL-C raising drugs: a peroxisome-activated receptor-α called LY18674, which proved such a failure that it will probably never get a name (

    ) , and an inhibitor of cholesteryl ester transferase, torcetrapib. Combined with a statin, this agent raised HDL-C in a Polish-American trial using ultrasound measurements of coronary atheroma and in a Dutch study of carotid atheroma in patients with hyperlipidaemia. But it also raised blood pressure, and neither …

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