"Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein". The New England Journal of Medicine. 2008. 359(21):2195-2207. PubMed • Full text • PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

Does rosuvastatin treatment reduce the incidence of major cardiovascular events in men and women with normal LDL levels but elevated C-reactive protein?

Bottom Line

Rosuvastatin significantly reduced the incidence of major cardiovascular events in apparently healthy persons with elevated high-sensitivity C-reactive protein and without hyperlipidemia.

Major Points

Guidelines

Updated guidelines should consider rosuvastatin therapy for primary prevention in individuals with elevated CRP.

Design

- Multicenter, randomized, double-blind, placebo-controlled trial
- N=17,802
- Rosuvastatin 20mg daily (n=8,901) vs. placebo (n=8,901)
- Median follow-up: 1.9 years (maximum: 5.0 years)
- Analysis: Intention-to-treat
- Primary outcome: Occurrence of major cardiovascular events defined as nonfatal myocardial infarction, nonfatal stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes.

Population

- Inclusion Criteria: Men ≥50 years and women ≥60 years with no history of cardiovascular disease, LDL cholesterol <130 mg/dL, high-sensitivity C-reactive protein ≥2.0 mg/L
- Exclusion Criteria: Previous use of lipid-lowering therapy, postmenopausal hormone replacement therapy, hepatic dysfunction, creatinine kinase >3x upper limit, diabetes, uncontrolled hypertension, inflammatory diseases, or recent drug/alcohol abuse.
- Baseline Characteristics: Varied population including 38.2% women and 25.2% Black or Hispanic; median LDL cholesterol 108 mg/dL.

Interventions

- Rosuvastatin 20 mg daily or matching placebo.

Outcomes

- Primary Outcome: Rosuvastatin reduced the rate of the primary endpoint by 44% compared to placebo (HR 0.56; 95% CI 0.46-0.69; P<0.00001).
- Secondary Outcomes: Significant reductions in the rates of myocardial infarction, stroke, arterial revascularization, and unstable angina. Modest but significant reduction in all-cause mortality with rosuvastatin.

Criticisms

- Early termination of the trial might have underestimated the rates of adverse events.
- Increased rate of physician-reported diabetes in the rosuvastatin group.

Funding

Supported by AstraZeneca.

Further Reading