Authors
LaRosa JC, Grundy SM, Waters DD, et al.
Title
Intensive lipid lowering with atorvastatin in patients with stable coronary disease.
References
N Engl J Med. 2005 Apr 7;352(14):1425-35
Background
Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes.
Purpose
To investigate the efficacy and safety of lowering LDL cholesterol levels below 2.6 mmol/L (100 mg/dL) in patients with stable coronary heart disease (CHD)
Design
  • Multicenter, randomized, double-blind trial
  • 10,001 patients ages 35-75 years with clinically evident CHD and LDL <3.4mmol/L
Exclusion Criteria
  • Hypersensitivity to statins
  • Uncontrolled diabetes
  • Any serious medical condition that would limit life expectancy <1 year
  • ALT >1.5x ULN
  • Uncontrolled hypothyroidism
  • CK >6x ULN
  • MI, previous or planned revascularization procedure within 1 month
  • LVEF <30%
  • Nephrotic syndrome, alcohol abuse, therapy with immunosuppressan
Follow-Up
Median 4.9 years
Treatment Regimen
  • Either atorvastatin 80mg or 10mg per day after 8 week run-in period
  • Follow up visits 12 weeks and months 6, 9, and 12 in the first year and then 6 months thereafter. Assessments included routine blood work and clinical interview
Results

Primary Endpoints

Atorvastatin (10mg)
n=5006		 Atorvastatin (80mg)
n=4995		 Hazard Ratio p
Major CV event (cardiac death, non-fatal MI or resuscitation after cardiac arrest, any stroke)
10.9 8.7 0.78 (0.69-0.89) <0.001

Secondary Outcomes

(see study for complete list)

  • Atorvastatin 80 mg vs. 10 mg: reduction in major coronary event [HR 0.80 (0.69-0.92); p=0.002, any coronary event [HR 0.79 (0.73-0.86); p=<0.001, stroke [HR 0.77 (0.64-0.93); p=0.007, hospitalization from congestive heart failure [HR 0.74 (0.59 to 0.94); p=0.01), and any cardiovascular event [HR 0.81 (0.75 to 0.87); p<0.001)
  • No difference in death from any cause.
Summary
Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase.