The "Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive
Protein" was published in the November 20, 2008 New England Journal of Medicine. This trial is
also known by the acronym JUPITER (Justification for the Use of Statins in Prevention: an
Intervention Trial Evaluating Rosuvastatin).
The trial was stopped early after a median
follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and it
was concluded "In this trial of apparently healthy persons without hyperlipidemia but with
elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the
incidence of major cardiovascular events."
The trial was financially supported by
Astra-Zeneca the maker of rosuvastatin. The Wall Street Journal reported that the JUPITER results
have been a "boon" to Astra Zeneca with sales of the drug rising 29% last year to $3.6
billion as rosuvastatin gained ground on other branded cholesterol drugs, including Pfizer Inc.'s
The media picked up that there was a 44% relative risk reduction in the
rosuvastatin group compared to those receiving placebo. Few in the media reported absolute risk
differences between the groups.
A CLOSER LOOK AT JUPITER
The primary outcome in
JUPITER was the occurrence of a first major cardiovascular event, defined as nonfatal myocardial
infarction, nonfatal stroke, hospitalization for unstable angina, an arterial revascularization
procedure, or confirmed death from cardiovascular causes.
At the time the study was stopped
(median followup, 1.9 years; maximal follow-up, 5.0 years), 142 first major cardiovascular events
had occurred in the rosuvastatin group, as compared with 251 in the placebo group.
DIFFERENCE FOR THE PRIMARY OUTCOME
The absolute risk difference between the rosuvastatin and
placebo groups is calculated at 1.22%. This translates to a Number Needed to Treat (NNT) of about 82
or 82 patients would need to be treated with rosuvastatin for 1.9 years to prevent one primary
RISK OF DEATH FROM ANY DEATH
This is an estimate calculated from the
published trial by taking apart the composite endpoint used in JUPITER. The absolute risk
difference for death from any cause was estimated at 0.55% between the groups. This is an NNT of
The New England Journal of Medicine conducted a two question online survey to gauge
readers' views of the JUPITER results. The first survey question asked "Do you believe, on the
basis of the JUPITER trial results, that the approach to laboratory screening of apparently healthy
adults should be changed? Respondents were split 49% answering yes and 51% no.
survey question asked "Do you believe, on the basis of the JUPITER trial results, that the
therapeutic use of statins in apparently healthy adults should be changed?" Again, the result
was split. The response was 48% yes and 52% no.
SHOULD JUPITER HAVE BEEN STOPPED
When there is clear evidence of benefit or harm ethically a trial should be
stopped and subjects offered the beneficial treatment or removed from one that is harmful. In the
JUPITER trial the absolute risks were so small the trial should have been continued to its planned
completion to allow for a full interpretation of the results.
Prematurely, ending a clinical
trial on ethical grounds of benefit can be used to market the treatment to those who do not
carefully evaluate the published results.
Students and pharmacists
investing a small amount of time in "studying a studying" and applying the principles of
interpreting clinical research could come up with markedly different views of the therapeutic value
of a drug than that reported in the general media.
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