Study Shows Dramatic Benefits from Statin Drug but Questions about Role of hs-CRP Test Remain

Treatment with a statin drug could significantly reduce cardiovascular problems in presumably healthy people who have normal but relatively high levels of high sensitivity C-reactive protein (hs-CRP), a marker of inflammation, according to a recent study.  Published in the Nov. 20 New England Journal of Medicine, the study shows that rosuvastatin helped decrease risk of major cardiovascular events in patients with increased results on hs-CRP tests but levels of low-density lipoprotein cholesterol (LDL-C or “bad” cholesterol) not usually felt to need treatment. Intensive therapy with rosuvastatin reduced cardiovascular events and stroke by 44 percent in this patient population. But because the study didn’t evaluate hs-CRP test results as a basis for prescribing rosuvastatin, its authors make no suggestions about using the test to guide treatment.

Investigators halted the trial less than 2 years into a planned 4-year study period after a safety monitoring committee noted the major reduction in the incidence of cardiovascular events among those patients who took rosuvastatin.

The research team, led by Paul M. Ridker, MD of Boston’s Brigham and Women’s Hospital and Harvard Medical School, studied nearly 18,000 men over age 50 and women over age 60. Patients were admitted to the study if their LDL-C level was less than 130 mg per deciliter (3.4 mmol per liter) and their hs-CRP level was 2.0 mg per liter or greater.

Half of the patients received 20 mg of rosuvastatin daily, while the other half received a placebo. Researchers followed these patients to see how many had heart attack, stroke, hospitalization for unstable angina, and death from cardiovascular causes. In addition to reducing the incidence of cardiovascular events and stroke, rosuvastatin lowered LDL-C by 50% and hs-CRP levels by 37%, researchers found.

Currently, doctors use hs-CRP levels to determine patients’ risk for cardiovascular events but not for deciding what treatment to use, writes Stanford University’s Mark Hlatky, M.D. in an accompanying editorial. He says the study does raise important questions: How should doctors use hs-CRP tests, and should statin therapy be prescribed to those with normal but relatively high hs-CRP levels?

The JUPITER trial results cannot answer these questions because it was a study of statin therapy, not hs-CRP, Hlatky adds. Answering these questions would require a study specifically designed to evaluate treatment guided by hs-CRP levels, he writes. Such a study would need to compare treatment decisions made for patients who are evaluated using the hs-CRP test with those who have not been tested. In addition, researchers would need to look at how treatment is guided by results of the hs-CRP test compared to other markers for cardiovascular risk such as homocysteine levels. While he suggested that it would also be necessary to evaluate the effect of treatment on those with low levels of hs-CRP, Dr. Ridker and colleagues point out that previous studies showed no benefit of statins in those with low levels of both hs-CRP and LDL-C.

The JUPITER findings also add fuel to an ongoing controversy about hs-CRP’s role in cardiac care, according to cardiologist and former National Institutes of Health Director Bernadine Healy, MD. “This [study] again points to an ongoing controversy: Does lowering CRP levels have a direct heart benefit, or is it only a marker of lower levels of the toxic and inflammatory LDL that goes into plaque?” she wrote in a U.S. News and World Report commentary about the study.

In her commentary, Healy pointed out that while rosuvastatin cut LDL-C levels in half among JUPITER patients, their hs-CRP levels fell by a more modest 37 percent, “leaving most patients with still-high CRP levels.” She urged patients and doctors to use caution when considering the findings of this study in deciding whether to use results of hs-CRP tests to guide rosuvastatin treatment.

Sources

Ridker, P et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. New England Journal of Medicine 2008; 359: 2195 - 2207.

Hlatky, M. Expanding the Orbit of Primary Prevention ‹ Moving beyond JUPITER. New England Journal of Medicine 2008; 359: 2280 - 2282.

Gore, J. Dawning of the Age of Jupiter? Cardiology Watch. Available online at http://cardiology.jwatch.org/cgi/content/full/2008/1110/1. Posted November 10, 2008. Accessed November 13, 2008.

Healy, B. Interpreting Jupter: Statins for Everyone? U.S. News and World Report. Available online at http://www.usnews.com/blogs/heart-to-heart/2008/11/10/interpreting-jupiter-statins-for-everyone.html. Posted November 10, 2008. Accessed November 13, 2008.

Tests: hs-CRP, Cardiac Risk Assessment
Conditions: Heart disease