JUPITER trial
Encyclopedia
The JUPITER trial is a study aimed at evaluating whether statin
s reduce heart attacks and strokes in people with normal cholesterol
levels.
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
.
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.
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.
, 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.
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
s reduce heart attacks and strokes in people with normal cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
levels.
Study rationale
JUPITER was a randomizedRandomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
double-blind
Double-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....
placebo-controlled study investigating the use of rosuvastatin
Rosuvastatin
Rosuvastatin is a member of the drug class of statins, used to treat high cholesterol and related conditions, and to prevent cardiovascular disease. It was developed by Shionogi.-Medical uses:The primary uses of rosuvastatin is for the treatment of dyslipidemia...
in the primary prevention of cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
. The trial focused on patients with normal low-density lipoprotein (LDL) cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
levels but increased levels of high-sensitivity C-reactive protein (hs-CRP). JUPITER was the first clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
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
Paul Ridker
Paul M. Ridker is a medical researcher and the Eugene Braunwald Professor of Medicine at Harvard University. He is also on staff at Brigham and Women's Hospital in Boston, Massachusetts. Dr. Ridker was included in TIME magazine's list of 100 most influential people of 2004. Previously, TIME and CNN...
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
Association (statistics)
In statistics, an association is any relationship between two measured quantities that renders them statistically dependent. The term "association" refers broadly to any such relationship, whereas the narrower term "correlation" refers to a linear relationship between two quantities.There are many...
with an increased risk of myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, peripheral arterial disease, and sudden cardiac death
Sudden Cardiac Death
Sudden cardiac death is natural death from cardiac causes, heralded by abrupt loss of consciousness within one hour of the onset of acute symptoms. Other forms of sudden death may be noncardiac in origin...
.
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 AssociationAmerican Heart Association
The American Heart Association is a non-profit organization in the United States that fosters appropriate cardiac care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke. It is headquartered in Dallas, Texas...
meeting and published in the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
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
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
, 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
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, and death at 1 year. The study's authors estimated that the number needed to treat
Number needed to treat
The number needed to treat is an epidemiological measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome...
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
AstraZeneca
AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...
, 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
Paul Ridker
Paul M. Ridker is a medical researcher and the Eugene Braunwald Professor of Medicine at Harvard University. He is also on staff at Brigham and Women's Hospital in Boston, Massachusetts. Dr. Ridker was included in TIME magazine's list of 100 most influential people of 2004. Previously, TIME and CNN...
, 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 genericGeneric drug
A generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...
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 randomizationMendelian randomization
In epidemiology, Mendelian randomization is a method of using measured variation in genes of known function to examine the causal effect of a modifiable exposure on disease in non-experimental studies...
, published in the Journal of the American Medical Association
Journal of the American Medical Association
The Journal of the American Medical Association is a weekly, peer-reviewed, medical journal, published by the American Medical Association. Beginning in July 2011, the editor in chief will be Howard C. Bauchner, vice chairman of pediatrics at Boston University’s School of Medicine, replacing ...
, 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.