Heart Disease: Not About Cholesterol?

The idea that lowering cholesterol is the key to preventing heart attacks and cardiovascular disease has taken a couple of big hits recently. The first came on Mar. 30, when a panel of cardiologists recommended that Zetia and Vytorin, cholesterol-lowering drugs marketed by a joint venture of Schering-Plough (SGP) and Merck (MRK), be used only as a last resort. The reason: A clinical trial adding Zetia to other cholesterol-reducing drugs had failed to show a benefit (BusinessWeek.com, 3/31/08).

But in the furor over Zetia and Vytorin, an equally dramatic but largely unnoticed development occurred the next day. On Mar. 31, AstraZeneca (AZN) announced that it was halting early a 15,000-patient trial of its cholesterol-lowering drug, Crestor—because the drug was working better than expected. The surprising twist: When the patients started taking the drug, their "bad" cholesterol levels were already very low—so low, in fact, that drugs normally would not have been recommended or used. Yet patients on the drug had fewer heart attacks than those untreated in the trial, which was dubbed Jupiter, and the benefit showed up much earlier than expected. "It was stunning to have Jupiter stopped so early," says Dr. James Liao, a researcher in the vascular medicine unit of Brigham & Women's Hospital in Cambridge, Mass., the lead research center for the trial. "It suggests a new paradigm. These drugs may be working in ways other than lowering cholesterol."