Epidemiology
Crestor slows plaque growth in low-risk patients
Last Updated: 2007-03-26 13:00:37 -0400 (Reuters Health)
By Bill Berkrot
NEW ORLEANS (Reuters) - AstraZeneca Plc's cholesterol drug Crestor significantly slowed build-up of plaque in the main artery supplying blood to the brain compared with a placebo in a two-year study of patients with early stage atherosclerosis at low risk for heart disease.
However Crestor, given at its 40-milligram high dose, failed to show statistically significant plaque reduction in this asymptomatic patient population, which would not normally qualify for therapy with the popular cholesterol medicines called statins, researchers said.
Results of the study were presented at the annual American College of Cardiology (ACC) scientific meeting on Sunday.
Several industry analysts had suggested that a demonstration of plaque regression in the low-risk population would enable AstraZeneca to differentiate its drug from other potent cholesterol fighters such as Vytorin, sold by Schering-Plough Corp. and Merck & Co.. If that is the case, results of the AstraZeneca-sponsored METEOR trial, while clearly positive, may represent a missed opportunity.
"These results are positive but not as positive as they could have been," Prudential Equities analyst Tim Anderson wrote in a research note. "We continue to believe that METEOR results will not have a meaningful impact on either Crestor or other cholesterol reducers."
Crestor, known chemically as rosuvastatin, had previously shown impressive plaque reduction in an earlier study of patients with advanced atherosclerosis. But even at high doses, showing regression in early-stage patients was a high bar to set.
"The results of the METEOR trial demonstrate that even in very low risk, asymptomatic individuals with modest subclinical atherosclerosis, rosuvastatin treatment can beneficially affect the atherosclerotic process," said Dr. John Crouse, the study's lead investigator from Wake Forest University.
In the 900-patient study, those taking Crestor experienced on average a 49 percent reduction in levels of LDL, or bad cholesterol, and an 8 percent increase in levels of HDL, the good cholesterol.
After two years, the thickness or narrowing of the carotid artery was statistically significantly less with Crestor -- -0.0014 millimeters per year vs +0.0131 mm/yr."
Significant plaque progression over the two-year study period was seen in the placebo group, researchers said.
"The result is provocative. It will not change (treatment) guidelines but it does raise a very important question which is: Can we prevent development of atherosclerosis by treating them very early in the course of their disease with a statin?," said Dr. Steven Nissen, chief of cardiology at Cleveland Clinic and the outgoing ACC president.
"In that sense it's successful, it met its prespecified end point and there are not a lot of trials here at this whole meeting that met their end point," Nissen said.
When it comes to new heart medicines, Nissen said, "we are in a drought and it's tough for those of us that treat patients."
While he said he won't be putting asymptomatic patients on Crestor on the basis of this study, he noted, "this adds to the understanding, and in that sense it's significant."
There were eight serious adverse cardiac events, or 1.1 percent, in the Crestor group versus none in the placebo group, but the overall frequency of reported adverse events was similar between the two groups, researchers said.
Crestor's launch had been hampered by early safety concerns. Sales have since taken off, reaching $2 billion last year, with the amassing of positive data from clinical trials and the absence of any new safety red flags.
"If the study reinforces a lack of significant safety concerns, we would expect continued market share momentum for Crestor despite the availability of generic Zocor," Bank of America analyst Chris Schott said in a research note prior to the ACC meeting.
