Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
Key result
Rosuvastatin targets vascular event prevention in patients with elevated hsCRP and normal lipids.
- HR 0.56
- 95% CI 0.46-0.69
- P<0.00001
- n=17,802
Why the study?
Does rosuvastatin 20 mg daily reduce major vascular events in apparently healthy men and women with LDL cholesterol <130 mg/dL and elevated high-sensitivity C-reactive protein (≥2.0 mg/L)?
Key Points
- Rosuvastatin significantly reduced major cardiovascular events in healthy individuals with elevated high-sensitivity C-reactive protein but normal cholesterol levels.
- Rates of the primary endpoint fell to 0.77 versus 1.36 per hundred person-years with daily rosuvastatin, yielding consistent reductions across all evaluated subgroups.
- Analysis of 17,802 participants randomly assigned to daily rosuvastatin or placebo evaluated occurrences of myocardial infarction, stroke, and cardiovascular death.
Study Design
Type
RCT (n=17,802)
Randomization
Randomly assigned
Structured PICO
Does rosuvastatin 20 mg daily reduce major vascular events in apparently healthy men and women with LDL cholesterol <130 mg/dL and elevated high-sensitivity C-reactive protein (≥2.0 mg/L)?
P
Population
17,802 apparently healthy men and women without hyperlipidemia (LDL-C <130 mg/dL) and elevated hs-CRP (≥2.0 mg/L), followed for a median of 1.9 years.
I
Intervention
Rosuvastatin 20 mg daily for a median of 1.9 years (maximum 5.0 years)
C
Comparator
Placebo
O
Outcome
Combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes over a median follow-up of 1.9 years (maximum 5.0 years)composite
Main Result
Hazard Ratio: 0.56 (95% CI 0.46–0.69)
Absolute Event Rate: 0.77% vs 1.36%
p-value: p=<0.00001
In apparently healthy individuals with normal LDL cholesterol (<130 mg/dL) but elevated hs-CRP (≥2.0 mg/L), rosuvastatin 20 mg daily reduced major cardiovascular events by 44% and all-cause mortality by 20%, though with a higher incidence of physician-reported diabetes.
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Our results are relevant for patient care and the prevention of heart attack and stroke. Physicians can no longer assume that patients are at low risk for heart disease simply because they have low cholesterol. We have confirmed that patients with increased hsCRP are at high risk even if cholesterol levels are low, and we now have evidence that a simple and safe therapy cuts that risk and saves lives.”
“We had hoped to see perhaps a 10 or 15 percent risk reduction. That would have told us that the inflammation hypothesis did have meaning. The observation here of a 45 or 50 percent reduction is just like a gift — it's a clinical gift, it's a research gift, and we're very excited about it.”
“These data demonstrate that women and men with elevated hsCRP who are otherwise at 5 percent to 20 percent 10-year risk had substantive risk reductions with statin therapy even though they are currently outside United States treatment guidelines.”
Implication
Supports statin initiation for primary prevention with elevated hsCRP; extends benefit to patients without hyperlipidemia.
Abstract
BACKGROUND: Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. METHODS: We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. RESULTS: The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. CONCLUSIONS: In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.)
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Cite This Study
Ridker et al. (2008) conducted an RCT in Elevated high-sensitivity C-reactive protein without hyperlipidemia (n=17,802). Rosuvastatin vs. Placebo was evaluated on Combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes (HR 0.56, 95% CI 0.46-0.69, p=<0.00001). Rosuvastatin 20 mg daily significantly reduced major cardiovascular events compared with placebo in adults with hs-CRP ≥2.0 mg/L and LDL-C <130 mg/dL (HR 0.56; 95% CI 0.46-0.69; P<0.00001).