Intensive lipid lowering with atorvastatin in patients with stable coronary disease.
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. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD).


METHODS
A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke.


RESULTS
The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality.


CONCLUSIONS
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 levels.
LaRosa
John C
JC
State University of New York Health Science Center, Brooklyn, NY 11203, USA.
Grundy
Scott M
SM
Waters
David D
DD
Shear
Charles
C
Barter
Philip
P
Fruchart
Jean-Charles
JC
Gotto
Antonio M
AM
Greten
Heiner
H
Kastelein
John J P
JJ
Shepherd
James
J
Wenger
Nanette K
NK
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin; D000410:Alanine Transaminase