Is prevention always better than cure?

After publication of the JUPITER Trial, physicians have to consider whether asymptomatic patients need CRP tests.

By Richard Young, M.D.

One of my residents, Brian Lindenmayer, M.D., recently approached me about a story he saw on NBC’s Today show. Its chief medical editor, Dr. Nancy Snyderman, finished her story on the recent JUPITER trial by telling her viewers to go their doctor immediately and demand a CRP test. Is this a good thing?

The JUPITER trial was recently published in the New England Journal of Medicine.(1) Its primary aim was to see if rosuvastatin (Crestor) would prevent coronary events in adults with a relatively low LDL level (< 130 mg/dL), but a raised CRP level (≥ 2.0 mg/L).

The researchers drew blood on 89,890 subjects initially.(2) Other patients who were not even considered included those with a history of previous lipid-lowering therapy, diabetes, elevated serum creatinine levels, or poorly controlled hypertension (diastolic > 100 mm Hg). Study subjects included men age 50 and older and women age 60 and older. Subjects were also excluded if they had other inflammatory conditions such as rheumatoid arthritis, lupus or active infections.

From the original 89,890 enrollees, only 17,802 were eventually included in the trial. Reasons for exclusion included a LDL level of > 130 (37,611), a high-sensitivity CRP level less than 2.0 (25,993), and a smattering of other reasons. The enrolled population had an average age of 66 years and included 38 percent women, 12.5 percent blacks and 12.7 percent Hispanics. This population was randomly assigned to take 20 mg of rosuvastatin per day or matching placebo.

This trial’s primary outcome was one of those combined outcomes cardiovascular trials love to report these days. It included the combined rate of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina or death from cardiovascular causes. The trial was originally planned to run for a median of four years of follow-up, but was stopped after a median follow-up of 1.9 years because of its significant findings.

There were 251 primary outcome events in the placebo group and 142 events in the rosuvastatin group (p < .00001). A further breakdown of the outcomes is listed in Table 1.

The only clinically significant adverse event reported to be more common in the rosuvastatin group was an increased risk of being newly diagnosed with diabetes (270 vs. 216, P=.01).

Now what?

Should family physicians change their current practice based on this study or should they wait for the next set of guidelines from the National Cholesterol Education Program? I think reasonable family physicians could disagree on this issue. As much as the evidence-based medicine movement wants treatment decisions to be objective, there is still judgment involved.

The argument for ordering routine CRP tests would center on the impressive reduction in bottom-line health events patients care about: strokes, heart attacks and death. One argument against it is the fact that there may be similar studies that found conflicting results, though there are none that I’m aware of.

The greatest limitation of this study is how limited its patient population was. How many late middle-age and elderly patients do you have who don’t have diabetes or difficult-to-control hypertension, but who do have elevated CRP levels? Probably not many. Therefore, the impact of widespread CRP screening is already limited just based on this study’s limited study population. Is it safe to expand the indications for CRP screening beyond the criteria listed in the JUPITER study? This is probably not a wise policy and the truth is no one knows.

Cost-effectiveness

The last point I want to make is that I imagine that many of the viewers who will take action will be young people who are relatively healthy and look nothing like the patients studied. I imagine that many of their family physicians will acquiesce to their demands and order a CRP test. Most will be normal, but I imagine a few of the young patients with an elevated CRP level will be started on rosuvastatin, whose cost is about $3.45 per day.(2)

Most laypeople and many physicians don’t realize that the whole program of screening patients for lipid disorders and treating them per NCEP guidelines raises health care costs in the short term and long term.(3,4) Adding one more screening test and one more reason to start an expensive drug will only exacerbate the exorbitant cost of American health care. The Today Show did not mention that reality in its broadcast.

If the media was more interested in telling the whole truth, the final admonition to its viewers would have sounded more like, “The JUPITER study had interesting findings. If you are within 10 years of 66 years of age, talk to your doctor about this. Very few of you who are not currently taking a statin will actually have a good reason to start a statin. And for all of us, our health care just got more expensive.”

That statement wouldn’t sell as much detergent or as many drugs, would it?

References

1. Ridker PM, et al. Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. NEJM 2208;359:2195-207.
2. Hlatky, MA. Expanding the orbit of primary prevention—moving beyond JUPITER. NEJM 2008;359:2280-1.
3. Goldman L, Weinstein MC, Goldman PA, Williams LW. Cost-effectiveness of HMG-CoA reductase inhibition for primary and secondary prevention of coronary disease. JAMA 1991;265:1145-51.
4. Prosser LA, et al. Cost-effectiveness of cholesterol-lowering therapies according to selected patient characteristics. Ann Int Med 2000;132:769-79.