Breakthrough at the Brigham

EVER SINCE cardiologists began focusing on high cholesterol levels as a risk factor for heart disease, they have had to deal with the troubling fact that half of all heart attacks and strokes occur in patients without high cholesterol levels or chest pains. One explanation for this is that even moderate levels of the artery-clogging substance can be dangerous if there is also a high level of inflammation in the blood vessels.

A new study led by a Brigham and Women's Hospital researcher shows that, in patients with normal cholesterol but high levels of inflammation, the use of a new-generation statin drug can reduce substantially the incidence of heart attacks, strokes, and deaths. The National Institutes of Health should organize an additional trial to determine if older and less-costly generic statins have the same effect.

To describe the potential impact of the Brigham study on cardiac preventive care, even doctors not involved in the study have used terms left over from the political campaign - "game-changing," "paradigm-shifting." Nearly 20 million Americans with high cholesterol levels are already taking statins. That number would grow by several million if doctors began prescribing them to individuals with moderate cholesterol but high levels of C-reactive protein, an indicator for arterial inflammation.

This would come at a great cost to the healthcare system - about $100 a month per patient. But, according to the data compiled by Brigham's Dr. Paul Ridker in his study of almost 18,000 participants in 26 countries, the benefits would also be great. Study participants taking AstraZeneca's statin Crestor had 54 percent fewer heart attacks and 48 percent fewer strokes. Deaths of any cause were 20 percent lower in this group compared with those taking the placebo. In addition, those taking Crestor were 46 percent less likely to need angioplasty or bypass surgery, offsetting the cost to the healthcare system of the statin prescriptions. Some statin users in the study did report an increase in new cases of diabetes, but overall the drug's benefit was significant.

AstraZeneca itself funded the Ridker study but played no role in the analysis or interpretation of its data, according to a statement on Brigham's website. Ridker and Brigham's stand to benefit from royalties on a test for C-reactive protein. Ridker said he had tried but failed to get the NIH to finance the study.

The director of the NIH's National Heart, Lung, and Blood Institute, Dr. Elizabeth G. Nabel, was cautious in her reaction to the Ridker results, pointing to the need for "large-scale, event-based randomized clinical trials" like Ridker's before a new approach to detect and treat a condition is adopted. Her own agency should now take the lead in such trials and should include in them less-costly generic statins.