METEOR supports statin treatment in low-risk patients

Over two years, rosuvastatin slowed rate of progression of carotid ntima-media thickness.

Issue: May 2007

NEW ORLEANS — Rosuvastatin 40-mg treatment over a two-year period slowed progression of maximum carotid intima-media thickness among middle-aged adults with a low Framingham risk and evidence of early atherosclerosis.

Progression was also slowed in every carotid segment with rosuvastatin (Crestor, AstraZeneca) compared with placebo, according to data presented by John R. Crouse III, MD, professor of medicine and public health sciences at Wake Forest University School of Medicine, Winston-Salem, N.C.

Crouse presented the results of the Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin (METEOR) study, a double blind, placebo-controlled, multicenter trial, at the 56th Annual American College of Cardiology Scientific Sessions. The results were also published in the Journal of the American Medical Association.

C. Noel Bairey Merz, MD, medical director and Endowed Chair of the Women’s Health Program and the Preventive and Rehabilitative Cardiac Center at Cedars-Sinai Medical Center, Los Angeles, said the study was well done.

“The study shows that patients that would not be identified by current screening guidelines (NCEP ATP III), do benefit from statin lipid lowering when screened with carotid intima media thickness for preclinical atherosclerosis, with the benefit being less progression of atherosclerosis measured by carotid intima media thickness,” she said.

Trial design

METEOR researchers originally screened 5,751 individuals but after exclusion criteria and loss to follow-up, they randomly assigned 876 volunteers to receive rosuvastatin 40 mg (n=624) or placebo (n=252) for two years. Inclusion criteria included men aged 45 to 70 and women aged 55 to 70; LDL cholesterol >120 mg/dL to <190 mg/dL with no coronary heart disease risk factor aside from age; or, LDL cholesterol >120 mg/dL to <160 mg/dL with >1 risk factor and a 10-year CHD risk of <10%, Crouse said. Other inclusion criteria included triglycerides <500 mg/dL and maximum carotid intima media thickness of at least 1.2 mm at any site, and <3.5 mm at all sites.

The researchers excluded high-risk patients.

The average participant was 57 and male. Thirty-two percent of patients in the statin group had two or more CHD risk factors vs. 39% in the placebo group. The mean LDL cholesterol was 155 mg/dL among participants assigned rosuvastatin and 154 mg/dL in the placebo group.

Researchers measured changes in the carotid bulb, common carotid artery, internal carotid artery sites and changes in 12 carotid sites.

METEOR results

Participants in the rosuvastatin arm had a 48.8% reduction in LDL cholesterol compared with a 0.3% reduction in the placebo group (P<.001).

The rosuvastatin group had a 0.0014 mm/y reduction in maximum carotid intima media thickness for the 12 carotid sites (95% CI, –0.0041 to 0.0014) compared with an increase in the placebo group (0.0131 mm/y, 95% CI, 0.0087-0.0174). For the maximum of the four common carotid sites, the rosuvastatin group had a 0.0038 mm/y reduction (95% CI, –0.0064 to –0.0013); for carotid bulb sites, a reduction of 0.0040 mm/y (95% CI, –0.0090 to 0.0010); and an increase of 0.0039 mm/y (95% CI, –0.0009 to 0.0088) for internal carotid artery sites, according to the study abstract.

The carotid intima media thickness change in the statin group, for the mean of the common carotid sites, was 0.0004 mm/y (95% CI, –0.0011-0.0019).

“The placebo group showed significant progression but no progression was observed in the rosuvastatin group. So [rosuvastatin] basically halted progression,” Crouse said.

The statin was well tolerated. Six patients had eight adverse events.

Final thoughts on METEOR

“METEOR provides new evidence of effects of rosuvastatin on atherosclerosis,” Crouse said. “It supports and extends the results of ASTEROID, the previous intravascular ultrasound study that showed regression of atherosclerosis in high-risk patients with established coronary artery disease. In contrast to ASTEROID, the METEOR population was low-risk and asymptomatic with early signs of atherosclerosis. In this group there was no evidence of disease progression across the two-year period.”

Including participants who were asymptomatic with lipid levels not requiring therapy in order to be able to include a placebo arm was considered a limitation of the study.

Other limitations included the focus on low-risk patients without advanced atherosclerosis, which Crouse said could have limited the ability to demonstrate disease regression.

Longer and larger randomized studies are needed to focus on clinical events to determine the clinical implications of METEOR’s findings, Crouse said.

“I found some of your limitations almost to be positives,” said session panelist Paul M. Ridker, MD, the Eugene Braunwald Professor of Medicine at Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital. “The fact that slowing of disease progression was observed in a low-risk population that we do not normally think about for statin therapy is important and strongly supports our ongoing hard endpoint in the JUPITER trial where rosuvastatin is being compared to placebo among apparently healthy individuals with low levels of LDL cholesterol but increased levels of CRP.”

Bairey Merz, who moderated the session, said after the meeting that the study brings up two questions.

“Does this reduction in carotid atherosclerosis, in these lower-risk patients, translate into a reduction in CVD events, specifically, does this strategy result in improved health?” she asked. “Second, what is the cost utility of this approach, specifically, what is the cost per year of life saved?” – by Judith Rusk

For more information:

Crouse JR III. Effect of rosuvastatin on progression of carotid intima media thickness in low-risk individuals: Results of the METEOR trial. Smaller late-breaking trials I. Presented at: The 56th Annual American College of Cardiology Scientific Sessions 2007; March 25-27, 2007; New Orleans.
Crouse JRIII, Raichlen JS, Riley WA, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis. JAMA. 2007;297:1344-1353.
Lauer MS. Primary prevention of atherosclerotic cardiovascular disease. JAMA. 2007;297:1376-1378.