What are the advantages and flaws of the JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial?

From the Guidelines

The JUPITER trial had a significant advantage in demonstrating the benefits of rosuvastatin in reducing cardiovascular events, but it also had several flaws, including early termination, a highly selective study population, and a modest absolute risk reduction, as noted in the 2019 ACC/AHA guideline on primary prevention of cardiovascular disease 1. The JUPITER trial showed that rosuvastatin 20mg daily reduced cardiovascular events by 44% in apparently healthy individuals with normal LDL cholesterol but elevated high-sensitivity C-reactive protein (hsCRP) levels. Some key points about the trial include:

• The trial was terminated early, potentially overestimating treatment benefits
• The study population was highly selective, excluding many patients typically seen in clinical practice
• The absolute risk reduction was modest (1.2% over 1.9 years) despite the impressive relative risk reduction
• Rosuvastatin was associated with a small but significant increase in diabetes risk
• The trial was industry-sponsored by the manufacturer of rosuvastatin, raising concerns about potential bias The 2019 ACC/AHA guideline on primary prevention of cardiovascular disease noted that the JUPITER trial achieved greater LDL-C lowering and greater reductions in ASCVD outcomes, with an acceptable safety record 1. Key aspects of the trial's findings and limitations should be considered when applying JUPITER findings to broader patient populations or using hsCRP as a screening tool for statin therapy, particularly in the context of the guideline's recommendations on LDL-C-lowering therapy and ASCVD prevention 1.

From the FDA Drug Label

The Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, the effect of Atorvastatin on the occurrence of major CV disease events was assessed in 17,802 males (≥50 years) and females (≥60 years) who had no clinically evident CV disease, LDL-C levels <130 mg/dL and hsCRP levels ≥2 mg/L.

Rosuvastatin significantly reduced the risk of major CV events (252 events in the placebo group vs. 142 events in the rosuvastatin group) with a statistically significant (p<0. 001) relative risk reduction of 44% and absolute risk reduction of 1. 2%

The advantages of the Jupiter trial include:

• Reduced risk of major CV events: Rosuvastatin significantly reduced the risk of major CV events by 44% compared to placebo.
• Consistent risk reduction across subgroups: The risk reduction for the primary end point was consistent across predefined subgroups, including age, sex, race, smoking status, and family history of premature CHD.

The flaws of the Jupiter trial include:

• Increased risk of diabetes mellitus: There was a significantly higher frequency of diabetes mellitus reported in patients taking rosuvastatin (2.8%) versus patients taking placebo (2.3%) 2.
• Limited generalizability: The study population had a specific set of characteristics, including no clinically evident CV disease, LDL-C levels <130 mg/dL, and hsCRP levels ≥2 mg/L, which may limit the generalizability of the results to other populations.

From the Research

Advantage of Jupiter Trial

• The Jupiter trial demonstrated that rosuvastatin 20 mg significantly reduced the rate of first major cardiovascular events among apparently healthy individuals with low-density lipoprotein cholesterol (LDL-C) levels below 130 mg/dL, but with hs-CRP levels of 2 mg/L or higher 3.
• The trial showed a 44% reduction in the primary composite endpoint, which included non-fatal myocardial infarction, non-fatal stroke, admission for unstable angina, arterial revascularisation, or cardiovascular death 3, 4.
• Rosuvastatin reduced LDL cholesterol by 50% and hs-CRP by 37%, resulting in a significant reduction in cardiovascular events, including total mortality 4.
• The trial provided important and clinically relevant information on primary prevention among patients who do not currently qualify for lipid-lowering therapy, including women and individuals with metabolic syndrome 5.

Flaws of Jupiter Trial

• The trial was stopped after a median follow-up of 1.9 years due to an imbalance in favor of the rosuvastatin group, which may have affected the overall results 4.
• The design of the trial did not allow for discrimination between the effects of reducing LDL cholesterol and hs-CRP on cardiovascular events 4.
• The trial reported a higher incidence of physician-reported diabetes in the rosuvastatin group compared to the placebo group, which may be a potential adverse effect of rosuvastatin therapy 4.
• The trial's results may not be generalizable to all populations, as it was conducted in a specific group of individuals with elevated hs-CRP and low LDL-C levels 5, 3.