From the Guidelines
The JUPITER trial was not used further because it had already achieved its primary objective of demonstrating the cardiovascular benefits of rosuvastatin in individuals with normal LDL cholesterol but elevated high-sensitivity C-reactive protein (hsCRP) 1. The trial's early termination after a median follow-up of 1.9 years was due to the clear reduction in cardiovascular events, making it ethically necessary to stop the placebo arm and provide the beneficial treatment to all participants. Key findings from the JUPITER trial include:
- A 44% reduction in the primary endpoint, including heart attack, stroke, and cardiovascular death
- No significant difference in the rates of myopathies or muscle disorders between men and women, regardless of treatment assignment
- No increase in cancer deaths in women, although the trial was stopped early The trial's results were incorporated into subsequent cardiovascular risk assessment tools and treatment algorithms, leading to expanded statin therapy recommendations for primary prevention in patients with normal cholesterol but elevated inflammatory markers 1. Some of the key considerations in the decision to stop the trial include:
- The significant reduction in cardiovascular events, which outweighed the potential risks and benefits of continuing the trial
- The ethical necessity of providing the beneficial treatment to all participants
- The incorporation of the trial's results into clinical practice guidelines and treatment algorithms, making further continuation of the original trial design unnecessary.
From the FDA Drug Label
The JUPITER study was stopped early by the Data Safety Monitoring Board due to meeting predefined stopping rules for efficacy in rosuvastatin-treated subjects
The study was stopped early due to meeting predefined stopping rules for efficacy, which means that the treatment was showing significant benefits and it was deemed unethical to continue the study and withhold the treatment from the placebo group.
From the Research
Reasons for Not Continuing the Jupiter Trial
- The Jupiter trial was stopped early, which may have led to an overestimation of the treatment benefit and an underestimation of the risk, making it difficult to reliably assess the cost-effectiveness of primary prevention with rosuvastatin 2.
- The trial had limitations, such as the exclusion of patients with low levels of high-sensitivity C-reactive protein (hsCRP), which made it impossible to assess whether baseline hsCRP modifies treatment response to statins or whether it identifies patients most likely to benefit from statin therapy 2.
- The trial's results may not be generalizable to all populations, as it only included individuals with average to low levels of low-density lipoprotein (LDL) cholesterol and elevated high-sensitivity C-reactive protein (hs-CRP) 3.
Alternative Lipid-Lowering Therapies
- Other studies have investigated the efficacy and safety of switching from low-dose statin to high-intensity statin for primary prevention in type 2 diabetes, finding that high-intensity statin therapy can significantly reduce plasma LDL-C levels, but may be associated with a higher risk of adverse events 4.
- The use of PCSK9 inhibitors, which can reduce LDL-C by 50-60% above that achieved by statin therapy alone, has been shown to be effective in reducing cardiovascular events and all-cause mortality in patients with clinical atherosclerotic cardiovascular disease (ASCVD) 5.
Limitations of the Jupiter Trial
- The trial's early termination and limitations in its design and population may have limited its ability to provide a complete understanding of the benefits and risks of rosuvastatin therapy 2.
- The trial's results should be interpreted with caution, taking into account its limitations and the potential for bias, and should be considered in the context of other available evidence on lipid-lowering therapies 6, 3, 2.