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

Study rationale[edit]

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.[1][2] The trial, which began in 2003, was directed by Paul Ridker of Brigham and Women’s Hospital.[3]

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.[4] 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.[4]

Study details[edit]

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 (NEJM) 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 one year.[5][6][7] The study's authors estimated that the number needed to treat with rosuvastatin to prevent one cardiovascular event was 95 over two years, extrapolated to 25 over five years. The trial was stopped early, after just 1.9 years median duration, by the study's Independent Data Monitoring Board, because the interim results met the study's predefined stopping criteria (it had been predetermined that it would be unethical to continue the study once it became clear that the patients in one arm of the study had a significantly higher cardiovascular risk than the other arm's patients).[1][8]

The trial was sponsored by AstraZeneca, the marketer of Crestor (rosuvastatin).[3] The company saw an increase in its share of the U.S. statin drug market following the November 2008 NEJM publication.[9]

Adverse events[edit]

Reports of serious adverse events within JUPITER were equally distributed between the study's rosuvastatin and placebo arms. There were no significant differences between the treatment groups with respect to muscle pain, muscle weakness, hepatic function, or renal function; however, the researchers noted small but statistically 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.[5][8] Those latter findings, 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, have been cited by those urging caution before expanding indications for statin treatment.[10][11][12][13]

Criticism of the trial[edit]

In 2010, Dr. Michel de Lorgeril, et al., published "a critical reappraisal" of the JUPITER Trial in the Archives of Internal Medicine. The article's authors critiqued what they saw as flaws in the trial, pointing out that the cardiovascular mortality rate and the case-fatality rate for myocardial infarction were much lower than they expected. They also raised concerns about conflict of interest in the trial design and leadership: nine of 14 authors of the main report had financial ties to the sponsor, AstraZeneca, and the lead investigator held the patent for the C-reactive protein test, whose use in screening would be promoted by the results as reported.[14] They also argued that the trial's premature termination may have distorted the results, and raised concerns that AstraZeneca scientists had controlled and managed the raw data. They concluded that, "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."[14]

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; the results may argue against CRP's use as a marker of cardiovascular disease risk or for identifying subjects for statin therapy as in JUPITER, and more strongly argue against using CRP as a therapeutic target per se.[15] 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.[16]


  1. ^ a b "JUPITER: Using hsCRP to identify primary prevention patients who may benefit from statin therapy", Endocrine Today, 25 November 2008
  2. ^ Myat, Aung; Gershlick, A. H.; Gershlick, Tony (2012). Landmark Papers in Cardiovascular Medicine. Oxford University Press. p. 35. ISBN 978-0-19-959476-4.
  3. ^ a b JUPITER trial information page, Brigham and Women’s Hospital
  4. ^ a b 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.
  5. ^ a b 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.
  6. ^ "To combat plaques, research targets inflammation-fighting statins"[dead link], Los Angeles Times, 8 December 2008
  7. ^ "Treating elevated C-reactive protein with a statin", Endocrine Today, 1 December 2008
  8. ^ a b Paul M Ridker, MD, MPH (May 2009). "The JUPITER Trial: Results, Controversies, and Implications for Prevention". Circulation: Cardiovascular Quality and Outcomes. 2009, 2 (3): 279–285. doi:10.1161/CIRCOUTCOMES.109.868299. PMID 20031849. S2CID 2271425.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ "Astra's Crestor gets sales boost after positive data", Reuters, 24 November 2008
  10. ^ 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.
  11. ^ "Dramatic JUPITER Findings Fail to Sway Prescribing Behavior, Poll Shows", press release, MarketWatch, 25 November 2008
  12. ^ 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.
  13. ^ 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.
  14. ^ a b de Lorgeril, M (2010). "Cholesterol Lowering, Cardiovascular Diseases, and the Rosuvastatin-JUPITER Controversy: A Critical Reappraisal" (PDF). Arch Intern Med. 170 (12): 1032–1036. doi:10.1001/archinternmed.2010.184. PMID 20585068.
  15. ^ 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.
  16. ^ Kolata, Gina (June 30, 2009). "Study Dismisses Protein's Role in Heart Disease". New York Times. Retrieved July 1, 2009.

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