JUPITER Trial Demonstrates Effectiveness of Statin Therapy in Reducing Cardiovascular Events among Healthy Patients

November 10, 2008 By Scott P. Williams [mailto:swilliams@perfuse.org]

New Orleans, LA: The results of the JUPITER trial suggest that rosuvastatin effectively reduces the occurrence of myocardial infarction (MI), stroke, and cardiovascular death among patients who have low LDL levels but elevated high sensitivity C-reactive protein (hsCRP) levels. The results were released at the American Heart Association’s 2008 Scientific Sessions.

According to the current prevention guidelines, patients with average or low LDL levels are not considered optimal candidates for statin therapy, but nearly half of MIs and strokes occur in this patient population. Previous work has also established that high hsCRP levels are associated with an increased risk of vascular events, and that statin therapy can help reduce hsCRP levels.

The JUPITER trial was an international randomized double blind placebo controlled examination of the efficacy of rosuvastatin for the prevention of cardiovascular events among patients with low LDL levels (LDL < 130 mg/dL) and elevated hsCRP levels (hsCRP ≥ 2 mg/L). The study enrolled 17,802 men and women who had no prior history of cardiovascular disease or diabetes mellitus. Following a 4-week run-in patients were assigned to either 20 mg daily dose of rosuvastatin or a placebo and were monitored supposed to monitored for 3.5 years, but the trial was ended after 1.9 years due to overwhelmingly positive results. Baseline characteristics and safety outcomes were similar in sets of patients.

Patients who received rosuvastatin demonstrated a 44% reduction in the occurrence of the trial’s primary endpoint of MI, stroke, unstable angina/revascularization, and cardiovascular death (HR 0.56; 95% CI, 0.46-0.69; P<0.00001) during the nearly two year period of the study. When viewed individually, the occurrence of MI and stroke were both significantly lower among patients who received rosuvastatin. There were 31 cases of MI among patients who received rosuvastatin versus 68 in patients who received a placebo (HR 0.46; 95% CI, 0.30-0.70; P<0.0002). Similarly, there were 33 incidences of stroke among rosuvastatin patients versus 64 among those who received a placebo (HR 0.52; 95% CI, 0.34-0.79; p<0.002). All cause mortality, a secondary endpoint of the trial, was 20% lower among patients who received the daily statin therapy (HR 0.80; 95% CI, 0.67-0.97; P=0.02). The study’s authors noted that these benefits of rosuvastatin were consistent among all of the sub-group analyses performed, including age, sex, and ethnicity.

The authors concluded that a new evidence based guideline for the use of preventative statin therapy should call for the treatment of men and women over the age of fifty if they: are diabetic; have LDLC > 160 mg/dL; have hsCRP > 2 mg/L.

However, because the trial is evaluating an agent that dramatically lowers LDLC as well as hsCRP, it can't directly answer whether CRP reduction alone leads to reduced cardiovascular risk. This hypothesis will require testing of agents with targeted vascular anti-inflammatory effects that lack proven beneficial effects (ie. a LDLC reduction).

The JUPITER trial was a physician initiated trial, which was funded by AstraZeneca. Dr Ridker is a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to Dade-Behring and AstraZeneca.

Download the JUPITER slides here

Access Dr Ridker's multimedia presentation here