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Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein
Paul M Ridker1, Eleanor Danielson, Francisco A H Fonseca
1Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. pridker@partners.org
Insights
Rosuvastatin significantly reduced major cardiovascular events in apparently healthy individuals with elevated high-sensitivity C-reactive protein (hs-CRP) but without hyperlipidemia. This statin therapy offers a new preventive strategy for individuals at risk of heart attack and stroke.
Area of Science:
- Cardiology
- Preventive Medicine
- Pharmacology
Background:
- Elevated high-sensitivity C-reactive protein (hs-CRP) is a predictor of cardiovascular events.
- Statins effectively lower both cholesterol and hs-CRP levels.
- A hypothesis was formed that statin therapy might benefit individuals with elevated hs-CRP but normal lipid profiles.
Purpose of the Study:
- To investigate the efficacy of rosuvastatin in reducing cardiovascular events in apparently healthy individuals with elevated hs-CRP and low-density lipoprotein (LDL) cholesterol levels below 130 mg/dL.
- To evaluate the impact of rosuvastatin on primary endpoints including myocardial infarction, stroke, revascularization, unstable angina, and cardiovascular death.
Main Methods:
- A randomized, placebo-controlled trial involving 17,802 participants.
- Participants received either 20 mg of rosuvastatin daily or a placebo.
- Follow-up was conducted to monitor the occurrence of major cardiovascular events.
Main Results:
- Rosuvastatin significantly reduced LDL cholesterol by 50% and hs-CRP by 37%.
- The primary composite endpoint occurred at significantly lower rates in the rosuvastatin group (0.77 per 100 person-years) compared to placebo (1.36 per 100 person-years), hazard ratio 0.56.
- Significant reductions were observed for myocardial infarction, stroke, revascularization/unstable angina, and cardiovascular death; all-cause mortality was also reduced. A higher incidence of physician-reported diabetes was noted in the rosuvastatin group.
Conclusions:
- In apparently healthy individuals without hyperlipidemia but with elevated hs-CRP, rosuvastatin significantly decreased the incidence of major cardiovascular events.
- Rosuvastatin demonstrates a favorable risk-benefit profile for primary prevention in this specific population.
- The study provides evidence for the use of statins in individuals identified by inflammatory biomarkers, not solely lipid levels.
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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