Advances & Insights: Neurosciences
January 6, 2009
What the news means for you
Michael R. Dobbs, MD
New research could change way doctors prescribe statins
The findings of the JUPITER trial are exciting, but I’m cautiously optimistic about the results. It’s very interesting that the researchers studied these agents in people who customarily wouldn’t be prescribed statin-type drugs, people whose LDL level is below 130.
They weren’t scientifically testing high-sensitivity CRP levels as a marker for cardiovascular events. They just assumed such levels are a marker, based on prior tests, but more investigation into that issue is probably needed. The hypothesis is that CRP signals inflammation within the blood vessels, indicating the danger of clot formation - especially in the areas of plaque - and leading to vascular events such as a stroke.
“Kentucky is part of the ‘stroke belt’ - We rate high in all the risk factors, including high blood pressure, obesity, high cholesterol and smoking.”
Probably not everyone needs to get a high-sensitivity CRP test. It’s still rather expensive and hasn’t yet been widely validated and accepted. It’s used most commonly in people who are thought to have an intermediate-level risk of vascular disease to determine whether they should have drug therapy. Maybe in the future the high sensitivity CRP test will become routine, along with cholesterol screening, but the present study doesn’t make that conclusion. The researchers didn’t study statins in people without a high CRP level.
The principal investigator in JUPITER, Paul M. Ridker, MD, is a co-inventor of one high-sensitivity CRP test, although there’s no indication of bias in the study.
Who should take statins
This study will motivate neurologists to be more aggressive with our stroke patients in prescribing statin agents. We’ve always strongly suspected, based on other trials, that statin drugs have benefits beyond lowering cholesterol, that they actually have anti-inflammatory benefits that reduce the risk of further vascular events like stroke. The JUPITER trial lends more evidence to that idea, and I think it will perhaps provoke physicians to have a lower threshold for treatment than they might have had in their patients.
A level of 130 LDL is not high enough for routine treatment in asymptomatic people. However, based on clinical trials, it is recommended that we bring that LDL level to below 70 in patients who’ve had a stroke or heart attack.
All statins reduce cholesterol levels. Crestor, the drug tested in the trial, is one of the more expensive and isn’t available in generic form. Perhaps it is better than another in lowering CRP, but I’m not likely to change the way I prescribe statins for my patient population. I would like to see a trial in which multiple statins are tested.
The seriousness of stroke
Stroke is the No. 3 cause of death in the United States and the leading cause of long-term disability. People who have had a stroke are also at a greater risk of dying from a heart attack.
The number of people in the United States who have a stroke is growing, with up to 800,000 new patients a year. Part of the reason is that people are living longer, but there is also more obesity and we’re still not recognizing and treating high blood pressure in our patients. Treating everyone who has high blood pressure could theoretically prevent half the strokes in this country.
Kentucky is part of the ‘stroke belt’, - as is much of the Southeast. We rate high in all the risk factors, including high blood pressure, obesity, high cholesterol and smoking.
“We’ve always strongly suspected, based on other trials, that statin drugs have benefits beyond lowering cholesterol, that they actually have anti-inflammatory benefits that reduce the risk of further vascular events like stroke.”
If someone has a stroke, they've probably had vascular disease for many years. The focus should not only be on the agents such as statins to help prevent a stroke, but on early, primary prevention don't smoke, maintain a healthy weight, exercise regularly, keep blood pressure and cholesterol down.
Dr. Dobbs directs the neurology residency program and the UK Stroke Affiliate Network and is an assistant professor of neurology in the UK College of Medicine.
Study shows statins may help prevent strokes in wider population
Despite the fact that high levels of low-density lipoprotein, or LDL, have long been associated with cardiovascular events, half of all strokes and heart attacks occur in people with low LDL levels. Now, a large international study suggests that inflammation levels in the blood may be a better marker for cardiovascular events in this population and the cholesterol-fighting drugs could be beneficial.
The study involved 17,800 healthy men and women with low LDL levels (less than 130 mg/dL) who had high-sensitivity C-reactive protein (CRP) levels of 2.0 mg/L or more. Since cholesterol-fighting statins are known to reduce levels of CRP, the researchers wanted to find out whether these statins might help people with high CRP levels and low LDL levels.
The results were so striking that what was supposed to be a five-year trial was stopped after two years. Taking statins cut the risk of strokes and heart attacks in the study population by 50 percent. The findings of this study - called the JUPITER trial - were published in the Nov. 20, 2008, issue of The New England Journal of Medicine .
How the study was conducted
The double-blind, placebo-controlled, randomized clinical trial took place at 1,315 sites in 26 countries. Women in the diverse population were age 60 or older, while men were age 50 and older. Participants had no history of cardiovascular disease. All had LDL cholesterol levels of less than 130 mg/dL and a high-sensitivity CRP level of 2.0 mg/L or higher.
One group was given 20 mg of the statin rosuvastatin, marketed as Crestor®; another group was given a placebo. Among those taking rosuvastatin, LDL-cholesterol levels were cut in half, and CRP levels were reduced by 37 percent. Additionally, triglyceride levels dropped 17 percent from baseline among those treated with statin therapy. These effects persisted over the course of the study.
After two years, 142 first major cardiovascular events had occurred in the rosuvastatin group, as compared to 251 in the placebo group. The two study groups had no significant differences in incidents of muscle weakness, newly diagnosed cancer or disorders of hematologic, gastrointestinal, hepatic or renal systems. There was a slight increase in newly diagnosed cases of diabetes among those taking statins.
“A large international study suggests that inflammation levels in the blood may be a better marker for cardiovascular events in this population and the cholesterol-fighting drugs could be beneficial.”
The JUPITER authors acknowledge they did not study people with low CRP levels, primarily because previous research found no evidence that statins lower cardiovascular risk in people with neither hyperlipidemia (the presence of excess fats or lipids in the blood) nor elevated CRP levels. The researchers also note that, since the trial was stopped early, the effect of longer-term therapy should be considered.
The makers of Crestor, the pharmaceutical company AstraZeneca, sponsored the trial. Their product is considered the most potent statin on the market and has been associated with increased muscle deterioration and kidney problems, although there were no such problems with the JUPITER participants.
The data holds promise for spurring further research into the use of other drugs to inhibit inflammation and reduce the rates of vascular events. Additionally, the study has implications for marketing new CRP tests.
If the Food and Drug Administration approves rosuvastatin for patients with low levels of LDL and elevated CRP, the number of patients taking statins could increase significantly.
UK HealthCare Services - Kentucky Neuroscience Institute
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