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.
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.
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, extrapolated to 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.
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.
A Specific Critique of the Jupiter study and Contrasting results from other studies
In 2010, a highly critical assessment of the Jupiter study was published in the Archives of Internal Medicine. The study, by de Lorgeril et al., had this to say in its Abstract and Conclusion: "RESULTS: The trial was flawed. It was discontinued (according to prespecified rules) after fewer than 2 years of follow-up, with no differences between the 2 groups on the most objective criteria. Clinical data showed a major discrepancy between significant reduction of nonfatal stroke and myocardial infarction but no effect on mortality from stroke and myocardial infarction. Cardiovascular mortality was surprisingly low compared with total mortality-between 5% and 18%-whereas the expected rate would have been close to 40%. Finally, there was a very low case-fatality rate of myocardial infarction, far from the expected number of close to 50%. The possibility that bias entered the trial is particularly concerning because of the strong commercial interest in the study. CONCLUSION: The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors."
In addition, some prior and some subsequent studies have contrasted with the JUPITER trial results. 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, though it may still be a useful marker of cardiovascular disease risk. 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.
- "JUPITER: Using hsCRP to identify primary prevention patients who may benefit from statin therapy", Endocrine Today, 25 November 2008
- JUPITER trial information page, Brigham and Women’s Hospital
- Ridker PM; Jupiter Study, Group (November 2003). "Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: rationale and design of the JUPITER trial". Circulation 108 (19): 2292–7. doi:10.1161/01.CIR.0000100688.17280.E6. PMID 14609996.
- Ridker PM, Danielson E, Fonseca FA, et al. (November 2008). "Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein". N. Engl. J. Med. 359 (21): 2195–207. doi:10.1056/NEJMoa0807646. PMID 18997196.
- "To combat plaques, research targets inflammation-fighting statins", Los Angeles Times, 8 December 2008
- "Treating elevated C-reactive protein with a statin", Endocrine Today, 1 December 2008
- "Astra's Crestor gets sales boost after positive data", Reuters, 24 November 2008
- Kolata, Gina (June 30, 2009). "Study Dismisses Protein’s Role in Heart Disease". New York Times. Retrieved July 1, 2009.
- Hlatky MA (November 2008). "Expanding the orbit of primary prevention--moving beyond JUPITER". N. Engl. J. Med. 359 (21): 2280–2. doi:10.1056/NEJMe0808320. PMID 18997195.
- "Dramatic JUPITER Findings Fail to Sway Prescribing Behavior, Poll Shows", press release, MarketWatch, 25 November 2008
- Shishehbor MH, Hazen SL (January 2009). "JUPITER to Earth: A statin helps people with normal LDL-C and high hs-CRP, but what does it mean?". Cleve Clin J Med 76 (1): 37–44. doi:10.3949/ccjm.75a.08105. PMC 2836530. PMID 19122109.
- Mora S, Musunuru K, Blumenthal RS (February 2009). "The Clinical Utility of High-Sensitivity C-Reactive Protein in Cardiovascular Disease and the Potential Implication of JUPITER on Current Practice Guidelines". Clin. Chem. 55 (2): 219–28. doi:10.1373/clinchem.2008.109728. PMID 19095730.
- Elliott P et al. (2009). "Genetic Loci Associated With C-Reactive Protein Levels and Risk of Coronary Heart Disease". JAMA 302 (1): 37–48. doi:10.1001/jama.2009.954. PMC 2803020. PMID 19567438.