American and Japanese researchers designed the study to see if intense behavioral and medical intervention could provide greater benefits than those seen with moderate lifestyle change and statin therapy. "So we did an intensive study and found out that indeed these effects are additive and one can have a profound reduction in risk by combining both drugs, dosed to endpoint, and a strict diet," said Lance Gould, M.D., lead author.

Dosing to endpoint was defined as adjustment of statin doses until specific lipid targets were reached. In the current study, the targets were less than 90 mg/dL low-density lipoprotein cholesterol, greater than 45 mg/dL high-density lipoprotein cholesterol, and less than 100 mg/dL triglycerides.

Investigators evaluated 409 consecutive, unselected patients with stable coronary artery disease who underwent a positron emission tomographic scan at the beginning of the study and a follow-up scan an average of 2.6 years later. Researchers reviewed clinical outcomes an average of 5 years after the second scan. The patients were not randomized; they chose their treatment program and were categorized based on their actual compliance at the time the second scan was obtained.

Although 1 in 5 patients (20.3%) who followed standard treatment died or suffered a major cardiac event within five years, the rate for those who remained with the maximal therapy program was lower than 1 in 15 (6.6%). The death or major event rate for patients who failed to follow at least standard treatment was almost 1 in 3 (30.6%). Major cardiac events were defined as myocardial infarction, stroke, angioplasty procedure, or bypass surgery.

In addition to achieving substantial reductions in cardiac events and mortality, the researchers were able to document the progress of treatment and predict outcomes years later by using scans of blood flow to the myocardium. "There's nothing in the world that has ever been published that compares and can predict outcomes, or shows these kinds of changes," Gould said. He added that the noninvasive scans were superior even to arteriograms in their ability to show how well blood reaches each part of the myocardium.

"By following the changes in blood flow in the heart by [positron emission tomographic] imaging, one can actually predict the outcomes; and that's never been shown before, that in a two year to two-and-a-half year treatment period, where we took pictures of changes in the blood flow in the heart, the results actually predict what happens to you five years later. And the pictures parallel the intensity of treatment."

The maximal treatment program required substantial commitments by both patients and providers. Patients limited fat intake to less than 10 percent of total calories (compared with 20 to 30 percent fat permitted by the American Heart Association diet). In addition, participants dieted in order to reach their ideal weight and exercised for at least 30 minutes 4 or 5 days per week. "It's a very intense program. The follow up is very important. I see these people every month," Dr. Gould said.

Ronald G. Schwartz, M.D., who was not involved in the research, said the clinical benefits and predictive ability of the scans were impressive. "Never has a study quite put it all together as this one has," he said. Although he acknowledged that the non-randomized study design is controversial, Schwartz said it recognized that patient motivation and beliefs are key factors in the real world of clinical medicine.

However, William Parmley, M.D., who wrote an editorial, said that the unconventional study design means the effects of lifestyle changes and statin treatment cannot be separated. "The question addressed by the article is whether these two are additive to one another. Because this is not a randomized placebo controlled trial, they can not definitely answer the question. It is probable that both interventions were helpful. However, the greater benefit occurred in the group with more statin users, so that we can't distinguish whether the statin use alone was responsible for the benefit," he said.

Nevertheless, Parmley noted that the substantial benefits seen in the patients who pursued maximal treatment have led him to consider a stricter attitude with his own patients.

Although Gould agrees that further work is needed to determine the relative effects of statin medication and lifestyle changes, he believes his group’s results show that motivating patients to undertake intense action can have profound rewards in reducing the adverse effects of coronary artery disease.