JUPITER Trial: Statin Therapy for Elevated CRP

Ridker PM, Danielson E, Fonseca FA, et al. • N Engl J Med

Key Finding

Statin therapy reduces cardiovascular events by 44% in people with elevated CRP and normal LDL

Original title: “Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein (JUPITER trial)”

Plain English Summary

Landmark RCT of 17,802 participants showing rosuvastatin reduces cardiovascular events in people with elevated hsCRP even when LDL is normal. Demonstrated CRP identifies risk beyond cholesterol.

In-Depth Analysis

Background

Dr. Paul M. Ridker and the JUPITER Study Group published this landmark randomized controlled trial in the New England Journal of Medicine (PMID: 18997196, DOI: 10.1056/NEJMoa0807646), testing whether statin therapy benefits people with elevated CRP but normal LDL.

Study Design

Design: Randomized, double-blind, placebo-controlled trial Population: 17,802 healthy men ≥50 and women ≥60 years Entry criteria:

•LDL-C <130 mg/dL (relatively normal)
•hsCRP ≥2.0 mg/L (elevated inflammation) Intervention: Rosuvastatin 20 mg vs. placebo Follow-up: Median 1.9 years (stopped early for efficacy)

Key Findings

Primary endpoint (MI, stroke, revascularization, CV death):

Group	Events	Rate/100 py	HR (95% CI)
Rosuvastatin	142	0.77	0.56 (0.46-0.69)
Placebo	251	1.36	—

44% relative risk reduction (p < 0.00001)

Biomarker changes with rosuvastatin:

•LDL-C: −50% (to 55 mg/dL)
•hsCRP: −37% (to 2.2 mg/L)

Key insight: Benefit observed despite "normal" baseline LDL.

Mechanistic Insights

JUPITER demonstrated that:

•Inflammation (marked by CRP) identifies risk beyond LDL
•Statins have anti-inflammatory effects independent of LDL lowering
•CRP reduction may contribute to clinical benefit

Clinical Implications

This trial expanded statin candidacy to include:

•Intermediate-risk patients with elevated hsCRP
•Those with normal LDL but inflammatory risk

Metabolic Health Perspective

While JUPITER supported pharmaceutical intervention, the metabolic optimization perspective notes that lifestyle changes can also lower CRP. However, JUPITER validates CRP as a clinically meaningful target.