Other cholesterol-lowering drugs

Although it became clear that a change in diet had little effect on CHD, that did not end the scientists’ efforts to demonstrate that CHD could be prevented. If diet couldn’t do it, then intervention with drugs would provide the evidence. And since drugs could be controlled much more strictly, and used in conjunction with placebos, the findings would be more demonstrable. But the drugs used to reduce blood cholesterol have all proved to be something of a disaster.

Launched on the public in 1961, Triparanol causes the levels of blood cholesterol to fall by inhibiting the liver's ability to make cholesterol. Two years later it was with- drawn because of serious side effects. Luckily for triparanol's manufacturers, a public scandal was avoided as the media's attentions were focussed on another drug marketed at the same time and by the same company — thalidomide.

More recently, a number of other drugs have been the subject of extensive and expensive trials. First was Cholestyramine (Questran) which reduces cholesterol by interfering with digestion. The gall bladder manufactures bile acid from cholesterol, and the bile acid is used in the intestine to digest fats. But when the drug is present in the gut, it binds with the bile acid, removing it from its normal function. Because the drug is indigestible, it, together with the bile acid, is excreted and the gall bladder has to make more by drawing cholesterol from the bloodstream.

As the trial would be very expensive, the scientists examined 480,000 men over a period of three years to find suitable subjects. They had to be men in the coronary age group and with extremely high blood cholesterol levels. As such men are in the most vulnerable group, their chances of success were greatly increased.

The investigators confidently announced in advance that blood cholesterol levels would be lowered by an average of 28% and, after seven years, coronary heart disease would be reduced by 50% in the treatment group.

At the end of the trial, however, cholesterol levels had fallen by less than a quarter of that called for at the start and heart disease rates were hardly affected. The $142 million trial was a total flop. Even if it had proved a success, however, those participating were so unrepresentative of the population that the question of its efficacy for the typical adult would still have remained. Another flaw that became apparent was an increase in the incidence of oral-gastro-intestinal cancers which could not be dismissed as a random chance. In the Lipid Research Clinics trial there were 21 cases and 8 deaths from gastrointestinal cancer in those taking the drug, compared to 11 cases and just 1 death in the control group.


References
1. Lipid Research Clinics Coronary Primary Prevention Trial: I. Reduction in incidence of coronary heart disease. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. J A M A. 1984; 251: 351.
2. Committee of Principle Investigators: World Health Organization co-operative trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: the final mortality follow up. Lancet. 1984; ii: 379.