Statins and the Jupiter Trial

Below are some cumulative incidence curves also known as "failure curves" from the JUPITER trail. ​as the line rises, it indicates more negative events are happening to patients. You want the line to stay as low as possible.

The JUPITER trial was a randomized, double-blind, placebo-controlled study that enrolled 17,802 participants without cardiovascular disease but with elevated high-sensitivity C-reactive protein (hs-CRP), with a median follow-up duration of 1.9 years.

The JUPITER trial was stopped early at the recommendation of its Independent Data and Safety Monitoring Board after a median follow-up of 1.9 years (maximum follow-up 5 years) because of a 44% reduction in the trial primary endpoint of all vascular events (P<0.00001), a 54% reduction in myocardial infarction (P=0.0002), a 48% reduction in stroke (P=0.002), a 46% reduction in need for arterial revascularization (P<0.001), and a 20% reduction in all cause mortality (P=0.02; Figure 1).

You can see from the first image that Rosuvastatin, a lipid lowering medication of the statin class of drugs, drastically reduced the primary end point of any vascular eventls defined as any of the following:

• nonfatal myocardial infarction

• nonfatal stroke

• arterial revascularization

• hospitalization for unstable angina

• confirmed death from a cardiovascular cause).

It also clearly reduced all cause mortality

What is even more interesting is that even if the targets of therapy which were an LDL-c under 70 and an hsCRP under 2 were not reached, it still showed reduced incidence of cardiovascular events

Figure 5. Cumulative incidence of cardiovascular events in JUPITER in the placebo and rosuvastatin groups according to whether or not reductions in both LDLC and hsCRP were achieved.

Again with the long time horizon of ASCVD disease progression that starts in childhood, having this effect of protection in less than 5 years of therapy is remarkable.

​Let's get nerdy and delve into some more numbers:

In the JUPITER trial, the relative risk reduction (RRR) for all-cause mortality (ACM) with rosuvastatin compared to placebo was 20% (HR: 0.80, 95% CI: 0.67–0.97).

​As is our mantra, we don't want to look only at the relative risk without knowing the absolute risk. The absolute risk reduction (ARR) for all-cause mortality was 0.25% per year (rosuvastatin: 1.00% per year vs. placebo: 1.25% per year), translating to a number needed to treat (NNT) of 400 over the median follow-up of 1.9 years.​ This means that you need to treat 400 patients for one year to prevent one death.

We will talk more later on the number needed to treat and how to put the risks and benefits in perspective. 

​Note​ also, the rapid drop in participants as the study progressed. This can be seen in the decrease in numbers outlined in red on the graph above as you move left to right. These numbers represent the number of patients in the study at the time. 

​It is unclear to me if this marked decrease is because the study was stopped early, or if it is because there was a large drop out rate of patients. The first explanation would not have a strong effect on how I interpret the data, but the second explanation would require further investigation. I will look into this question and get back to you on a future blog post.

Until then, be well.

LINK TO PDF of PAPER

Ridker, P. M. (2009). The JUPITER trial: results, controversies, and implications for prevention. Circulation: Cardiovascular Quality and Outcomes, 2(3), 279-285.