ACC.07 Highlights: Panel discussion covering trials on lipids and atherosclerosis

Congress Reports

ACC.07: 56th Annual Scientific Session of the American College of Cardiology

ACC.07 Highlights: Panel discussion covering trials on lipids and atherosclerosis

MedWire ACC - (New Orleans, LA, USA) - March 27, 2007: Here, an informal convergence of 13 experts, with a mandate to debate and challenge key data were, presented at this year’s ACC Scientific Sessions and i2 Summit Meeting.

Here, Dr. John Stein (University of Wisconsin, Madison, WI, USA) briefly highlighted the outcomes from a number of vascular clinical trials presented at the ACC.07. He stated, “we really got bad news for drugs that attempted to raise HDL cholesterol (HDL-C) levels,” saying that the first drug, torcetrapib, which was tested in conjunction with atorvastatin in the ILLUSTRATE and RADIANCE I & II trials, was shown to raise HDL-C levels by approximately 60% and lower LDL-C levels by approximately 20%. However, this did not slow atherosclerosis progression.

He added that in the Effect of recombinant HDL on Atherosclerosis - Safety and Efficacy (ERASE) trial, the novel agent CSL111, was found to be no better than placebo at regressing atherosclerosis, although as Dr. Stein commented, “there were some signs of benefits in some of the secondary endpoints”.

Finally, he added, a powerful PPAR-97 agonist, LY518674, proved to be no better than a currently-used fibrate, but it also raised serum creatinine and had a very powerful and unusual dose response. While these data did not bring good news for HDL-raising agents, Dr. Stein suggested that “we have an excellent HDL-cholesterol-raising drug already available, which is niacin.”

In response, a panelist pointed out that “one of the most intriguing aspects of these data was the implication for surrogate endpoints, and given the progression of disease that was reported, it would appear that the surrogates may still provide a basic, quick, relatively inexpensive way to screen drugs.”

Concurring, Dr. Stein said that “by conducting morbidity and mortality trials in conjunction with imaging trials, the imaging trials really serve as a data safety monitoring referendum about agent safety,” in particular, if they are not shown to slow atherosclerosis, they may truly cause cardiac events.

The news was considerably better for drugs that do lower LDL-C. Dr. Stein reported that in METEOR, the benefits of statin therapy were extended to patients at apparent low risk (Framingham score <10%),>. He also said that a new drug, ISI 30102, was shown to lower LDL-C and triglycerides by 50% when added on top of statin therapy. “So, I think that this shows us that we’ve been on the right track,” said Dr. Stein. “It extends the population of patients in whom aggressive lipid-lowering therapy can be beneficial, and it provides some insight into what the future is going to look like - very specific compounds that go right to the liver and block Apo B production.”

Noting that METEOR was also good news for screening tests, Dr. Stein said that the study included patients who were apparently low risk with one risk factor, or two risk factors with Framingham score <10% for both groups. Despite having normal risk factors, they had increased carotid media thickness and responded positively to lipid-lowering therapy. Dr. Stein suggested that these data confirm that people with advanced atherosclerosis can benefit from aggressive lipid-lowering therapy. He also highlighted an additional study presented this week, suggesting that an abbreviated carotid IMT scan that just focuses on plaque screening and the common carotid artery could do just as well for clinical purposes as a research protocol.

Continuing, Dr. Stein stated how the MESA data showed that increased coronary calcium predicted future cardiac events in four major US ethnic groups, and that importantly, this filled in a major gap in the literature with regards to offering data on a large, relatively unselected group of people that included African Americans, Hispanic Americans, and Asian Americans. And finally, he noted “the Dallas Heart Study wraps it up, and shows us that up to a third of patients with calcium scores above 400, actually have low Framingham risk scores.”

When asked by another panelist about the direction of statin therapy in light of data in low-risk patients, Dr. Stein commented that “we need to be smarter about identifying who, among low-risk patients, need to be treated.”

“After all,” he said, “most heart attacks occur in people who are at low-risk. And perhaps noninvasive imaging and perhaps some new biomarkers can help us be smarter about who we treat rather than just treating more people.”