The second trial was the $150 million Lipid Research Clinics (LRC) Coronary Primary Prevention Trial. The trial was led by Basil Rifkind of the NHLBI and Daniel Steinberg, a specialist on cholesterol disorders at the University of California, San Diego. The LRC investigators had screened nearly half a million middle-aged men and found thirty-eight hundred who had no overt signs of heart disease but cholesterol levels sufficiently high—more than 265 mg/dl—that they could be considered imminently likely to suffer a heart attack. Half of these men (the control group) were told to eat fewer eggs and less fatty meats and drink less milk, and were given a placebo pill to take daily. The other half (the treatment group) were counseled to eat the same cholesterol-lowering diet, but they were also given a cholesterol-lowering drug called cholestyramine. Both groups had been told to diet, because the LRC investigators considered it unethical to withhold all treatment from the control group, given their high cholesterol levels and high risk of heart disease. It was an odd decision for two reasons. First, the LRC trial had been approved in the early 1970s in lieu of the National Diet-Heart Study that was necessary to establish the safety and effectiveness of a cholesterol-lowering diet; the LRC investigators had no proof that such a diet would benefit their subjects, rather than harm them. Second, both groups were told to diet, the trial could determine only the effectiveness of the drug—the single variable that differed between them.

In January 1984, the results of the trial were published in The Journal of the American Medical Association. Cholesterol levels dropped by an average of 4 percent in the control group—those men taking a placebo. The levels dropped by 13 percent in the men taking cholestyramine. In the control group, 158 men suffered nonfatal heart attacks during the study and 38 men died from heart attacks. In the treatment group, 130 men suffered nonfatal heart attacks and only 30 died from them. All in all, 71 men had died in the control group and 68 in the treatment group. In other words, cholestyramine had improved by less than .2 percent the chance that any one of the men who took it would live through the next decade. To call these results “conclusive,” as the University of Chicago biostatistician Paul Meier remarked, would constitute “a substantial misuse of the term.” Nonetheless, these results were taken as sufficient by Rifkind, Steinberg, and their colleagues so they could state unconditionally that Keys had been right and that lowering cholesterol would save lives.