Is JUPITER Also a God of Primary Prevention?

My Lord Jupiter knows how to sugarcoat the pill.

—Molière, Amphitryon (1666)

Although acronyms of clinical research trials may facilitate communication, enhance recall, and save time and space, they sometimes connote more than meets the eye, thereby creating the potential for favorable bias.¹ A prime example is the trial named JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin^*).²

In Roman mythology, Jupiter was king of the gods and the god of sky and thunder. Accordingly, any trial named JUPITER immediately brings to mind majesty, strength, and authority. For the most part, the JUPITER results fit that image, but whether they are as all powerful as their mythological namesake remains to be determined.

JUPITER was a randomized trial involving 17,802 apparently healthy middle-aged men and women who did not have hyperlipidemia but did have elevated levels of high-sensitivity C-reactive protein—an inflammatory biomarker. The events tallied were myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, and death from cardiovascular causes. After a mean follow-up of 1.9 years, the rate of a first major cardiovascular event was reduced by about 50% among participants given rosuvastatin daily compared with those given a placebo. The rate of deaths from any cause was also reduced significantly.

As soon as JUPITER's findings were released, one authority hailed the study as a “blockbuster” and its results as “paradigm-shifting.”³ An editorial accompanying the published trial predicted that “Guidelines for primary prevention will surely be re-assessed on the basis of the JUPITER results….”⁴ This, together with strong endorsements from the academic community,⁵ almost assures that statins in general, and rosuvastatin in particular, will be prescribed for millions of people worldwide in an effort to ward off cardiovascular events and death.^6,7 But translating JUPITER's findings immediately into clinical practice without first carefully considering their implications would not be prudent or appropriate.⁸

Advocates of primary prevention often fail to distinguish between population medicine and individual medicine. In population medicine, the subject being treated is precisely that—a population. The intervention, applied systematically to the entire group, does not necessarily benefit a given individual within the group. In JUPITER, for example, every John Doe had to take his rosuvastatin daily to spare one Mary Jones her heart attack. Furthermore, the rate of events in JUPITER was reduced from roughly 2 per 100 in the placebo group to about 1 per 100 in those taking rosuvastatin; that yields an absolute risk reduction of only about 1.2% for the study period. At that rate, 95 people would require treatment for 2 years to prevent a single event. Moreover, the absolute risk reduction that would be achieved after 5 years of treatment was estimated at only 4%.²

One final point: Although the rate of serious adverse events was the same in both groups, rosuvastatin—like any other statin—must be taken daily for the rest of the patient's life, requires intermittent monitoring with blood tests, may interact dangerously with other drugs, and, of course, is not free.

In conclusion, we believe that, from the standpoint of a population, JUPITER does qualify as a god of primary prevention. But population medicine differs substantially from individual medicine. Consequently, for any one individual—even one who has no hyperlipidemia but does have an elevated level of high-sensitivity C-reactive protein—JUPITER's findings offer only a small chance of benefit.