Authors

Ridker PM, Danielson E, Fonseca FA, et al.

Title

Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.

References

N Engl J Med. 2008 Nov 20;359(21):2195-207.

Background

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) predict cardiovascular events. Since statins lower levels of hsCRP as well as cholesterol, it is hypothesized that people with elevated hsCRP levels but without hyperlipidemia might benefit from statin treatment.

Purpose

To investigate whether treatment with a statin, as compared with placebo, would decrease the rate of first major cardiovascular events in individuals with LDL cholesterol below current treatment thresholds but with elevated hsCRP.

Design

Multicenter, randomized, double blinded placebo controlled trial
17,802 patients (men >50yrs; women >60) with a LDL-C <3.4mmol/L and hsCRP >2.0mg/L
No history of cardiovascular disease

Exclusion Criteria

Concurrent lipid lowering therapy
Use of post-menopausal HRT
Recent stroke, MI or amputation for vascular disease <6mos prior to study entry
Liver dysfunction (ALT >2x ULN)
CK >3x ULN
Type I/II diabetes
Uncontrolled hypertension (SBP >190mmHg; DBP >100mmHg)
History of inflammatory disease (SLE, RA etc.)
Alcohol abuse or use of immunosuppressant medications

Follow-Up

Median 1.9 years (max 5.0)

Treatment Regimen

Rosuvastatin 20mg/day or placebo
Follow-up visits scheduled at 13 weeks after randomization, then at 6 months, and then 6 monthly thereafter. Compliance, lipid and routine blood work assessed at each visit.

Results

Primary Endpoint

Rosuvastatin
n=8901
Rate per 100 person-yr Placebo
n=8901
Rate per 100 person-yr Hazard Ratio p

Combined cardiac death, non-fatal MI, non-fatal stroke, unstable angina, revascularization

0.77 1.36 0.56 (0.46-0.69) <0.0001

Secondary Outcomes

(see paper for complete list)

Rosuvastatin
n=8901
Rate per 100 person-yr Placebo
n=8901
Rate per 100 person-yr Hazard Ratio p

Cardiac death, MI, stroke

0.45 0.85 0.53 (0.40-0.69) <0.00001

Any stroke

0.18 0.34 0.52 (0.34-0.79) 0.002

Any MI

0.17 0.37 0.46 (0.30-0.70) 0.0002

Summary

In this trial of apparently healthy persons without hyperlipidemia but with elevated hsCRP levels, rosuvastatin significantly reduced the incidence of major cardiovascular events.