ORLANDO — Further analysis of results from JUPITER proved that cutting a person's C-reactive protein level with a statin lowers cardiovascular-event risk independent of a cholesterol effect.
The finding will likely pave the way toward wider use of the high-sensitivity C-reactive protein (hsCRP) test and result in many millions more people getting placed on a statin.
“The level that you get the hsCRP down to, and the level you get the LDL cholesterol down to, both predicted the benefits,” Dr. Paul M. Ridker, JUPITER lead investigator, said when he presented the findings at a press briefing during the annual meeting of the American College of Cardiology.
A second new analysis of data collected in JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) produced another important but unexpected finding: Treatment of the JUPITER enrollees with 20 mg/day of rosuvastatin (Crestor) resulted in a highly significant 43% relative drop in the risk for a first occurrence of pulmonary embolism or deep-vein thrombosis, a prespecified secondary end point of the study.
“The JUPITER trial turned out even better than anyone on the steering committee could have hoped for. It's a spectacular win for patients. This is a great way to save lives and do it in a cost-effective manner,” said Dr. Ridker, director of the center for cardiovascular disease prevention at Brigham and Women's Hospital in Boston.
The new analyses “will convince more physicians” of the value of screening hsCRP and starting a statin in people who fit the profile enrolled in JUPITER, said Dr. Deepak Bhatt, chief of cardiology at the Veterans Affairs Boston Healthcare System.
Measuring hsCRP “is a cheap and simple test that can put a person on a statin who might not otherwise get it, and it might reduce [his or her] mortality risk. That's pretty compelling. And there is no downside aside from cost,” Dr. Bhatt said.
“I don't anticipate the new statin-treatment guidelines [the fourth edition of the Adult Treatment Panel of the National Heart, Lung, and Blood Institute] that will be out in about 12 months will recommend routine use of hsCRP, but I think it will say it's an option,” said Dr. Roger Blumenthal, professor of medicine and director of the center for the prevention of heart disease at Johns Hopkins University in Baltimore.
“JUPITER tells us that [with statin treatment] you can have a major impact on reducing myocardial infarctions, strokes, VTEs [venous thromboembolisms], and all-cause deaths. It's very impressive,” said Dr. Blumenthal, a spokesman for the American Heart Association. Another effective way to reduce hsCRP levels is by a healthier diet and increased exercise, steps that should be instituted before a statin is begun, he added.
JUPITER enrolled 17,802 men aged 50 or older and women aged 60 or older during 2003-2006 at 1,315 sites in 26 countries. The participants had no history of cardiovascular disease, and at enrollment had a serum LDL cholesterol level of less than 130 mg/dL and an hsCRP level of 2.0 mg/L or higher. The LDL maximum was picked because people with this cholesterol level and no history of cardiovascular disease do not qualify for statin treatment by current U.S. standards. The hsCRP minimum was selected because it is roughly the current U.S. median level.
The study's primary finding, reported last November, was that the 20-mg/day rosuvastatin regimen produced an average 50% reduction in LDL cholesterol and an average 37% reduction in hsCRP, and was significantly associated with a relative 44% drop compared with placebo in the rate of major cardiovascular events during a median follow-up of 1.9 years (N. Engl. J. Med. 2008;359:2195-207). The study was primarily funded by AstraZeneca, which markets Crestor.
From the initial report it was unclear whether the benefit was driven mostly by the cut in LDL cholesterol, or whether the fall in hsCRP also played a major role in the outcome.
Dr. Ridker and his associates analyzed the outcome rates linked to several different achieved levels while people were on statin treatment. Those whose hsCRP fell below the prespecified target level of 2.0 mg/L but whose LDL cholesterol remained above the target, and those whose LDL cholesterol level fell below the prespecified target of 70 mg/dL but whose hsCRP remained above the target had roughly similar outcome rates that were reduced by about 36% compared with the people on placebo. Those who achieved LDL and hsCRP levels that were both below the target rates had even better outcomes, with a relative rate reduced by 65% compared with the placebo group.
The analysis also showed that people who achieved an hsCRP level of less than 1 mg/L along with an LDL of less than 70 mg/dL did even better, with a 79% cut in their event rate relative to placebo. And the reductions in hsCRP and LDL cholesterol were independent effects.
The second analysis reported at the meeting looked at the 94 VTEs that occurred during follow-up. Thirty-four of these episodes occurred in the rosuvastatin group and 60 occurred in the placebo arm, a statistically significant relative reduction of 43% for the statin compared with placebo, reported Robert J. Glynn, Sc.D., a biostatistician at Brigham and Women's Hospital.
Dr. Ridker and Dr. Glynn have received grant support from AstraZeneca, and Dr. Ridker also has received consulting and lecture fees from AstraZeneca and several other drug companies. Dr. Ridker has been listed as a coinventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers (such as hsCRP) in cardiovascular disease.
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