JUPITER trial

The JUPITER trial (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial) is a study aimed at evaluating whether statins reduce heart attacks and strokes in people with normal cholesterol levels.

Study rationale
JUPITER was a randomized double-blind placebo-controlled study investigating the use of rosuvastatin in the primary prevention of cardiovascular disease. The trial focused on patients with normal low-density lipoprotein (LDL) cholesterol levels but increased levels of high-sensitivity C-reactive protein (hs-CRP). JUPITER was the first clinical trial to indicate that statin therapy may provide benefit to patients with low-to-normal LDL levels and no known cardiovascular disease. The trial, which began in 2003, is directed by Paul Ridker of Brigham and Women’s Hospital.

Because half of all vascular events occur in patients with normal or low levels of LDL cholesterol, JUPITER was designed to determine whether hs-CRP testing could identify these patients, and whether statin therapy could prevent cardiovascular events among them. Elevated hs-CRP levels are thought to be a biomarker of inflammation, and have been associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death.

Study details
The trial analyzed 17,802 patients without evidence of heart disease but with high CRP levels. In 2008, results presented at the American Heart Association meeting and published in the New England Journal of Medicine found that patients with low-to-normal LDL cholesterol receiving rosuvastatin had a lower rate of major cardiovascular events. Compared to patients taking a placebo, patients given rosuvastatin had reductions in LDL and CRP levels, and a reduction of 0.2% to 0.6% in their absolute risk of heart attack, stroke, and death at 1 year. The study's authors estimated that the number needed to treat with rosuvastatin to prevent one cardiovascular event was 95 over 2 years, or 25 over 5 years. The trial was stopped early by the study's independent data and safety monitoring board because the interim results met the study's predefined stopping criteria.

The trial is sponsored by AstraZeneca, the marketer of Crestor (rosuvastatin). The company saw an increase in its share of the U.S. statin drug market following the November 2008 New England Journal of Medicine publication. The NEJM study's lead author, Paul Ridker, is the inventor of the CRP assay utilized in the study, and profits from its use.

Adverse events
The researchers noted small but significant increases in the rate of physician-reported diabetes and glycated hemoglobin values in the rosuvastatin group, an effect that has also been seen in studies with other statins. This finding, along with concerns over the safety of very low LDL levels, rosuvastatin's higher cost compared to generic statins, and the validity of biomarkers used in the diagnosis of cardiovascular disease, has been cited by those urging caution before expanding indications for statin treatment.

Contrasting results from other studies
Some subsequent studies have contrasted with the JUPITER trial results, particularly on the role of C-reactive protein. A 2009 study employing Mendelian randomization, published in the Journal of the American Medical Association, suggested that CRP does not play a causal role in cardiovascular disease. The discordant results of this subsequent study provoked debate over the role and value of CRP as a biomarker and possible therapeutic target in heart disease.