Authors
Cannon CP, Braunwald E, McCabe CH, et al.
Title
Intensive versus moderate lipid lowering with statins after acute coronary syndromes
References
N Engl J Med. 2004 Apr 8;350(15):1495-504
Background
Statins reduces the risk of death or cardiovascular events across a wide range of cholesterol levels whether or not patients have a history of coronary artery disease. The doses of statins used in clinical trials reduced low-density lipoprotein (LDL) cholesterol levels by 25 to 35 percent, and guidelines at that point recommended a target LDL cholesterol level of less than 2.59 mmol/L (100 mg/dL) for patients with established coronary artery disease or diabetes. It is not clear whether lowering lipid levels further would increase the clinical benefit.
Purpose
To compare the standard degree of LDL cholesterol lowering to approximately 2.59 mmol/L (100 mg/dL) with the use of 40 mg of pravastatin daily with more intensive LDL cholesterol lowering to approximately 1.81 mmol/L (70 mg/dL) with the use of 80 mg of atorvastatin daily as a mean of preventing death or major cardiovascular events in patients with an acute coronary syndrome.
Design
  • Multicenter, randomized, double-blind, double-dummy controlled trial
  • 4162 patients age >18 years who had been hospitalized for an ACS within the preceding 10 days
  • Total cholesterol < 6.2mmol/L
  • On optimal medical treatment and intervention strategy for an ACS
Exclusion Criteria
  • On any statin therapy at a dose of 80mg/day
  • On medications with strong cytochrome P-450 3A4 inhibition
  • Any serious medical condition that would limit life expectancy <1 year
  • Serious liver disease
  • PCI within the past 6 months or CABG within previous 2 months
  • CK >3x ULN
  • Cr > 177umol/L
Follow-Up
Mean 24 months (18-36 months)
Treatment Regimen
  • Pravastatin 40mg/day or atorvastatin 80mg/day
  • Follow up visits 30 days, 4 months and every 4 months thereafter. Assessments included routine blood work and clinical interview
  • LDL cholesterol levels were monitored, and the protocol specified that the dose of pravastatin was to increase to 80 mg in a blinded fashion if the LDL cholesterol level exceeded 3.23 mmol/L (125 mg/dL) on two consecutive visits
Results

Primary Endpoints

Pravastatin
n=2063		 Atorvastatin
n=2099		RRRp
Combined outcome: total death, MI, angina wit hospitalization, PCI or CABG, and stroke
26.3%22.4%16%0.005
Pravastatin median LDL (2.46mmol/L); atorvastatin (1.60mmol/L) p<0.001

Secondary Outcomes

(see study for complete list)

Atorvastatin group: cardiac death, MI or revascularization reduced by 14%; p=0.029, need for revascularization reduced by 14%; p=0.04, recurrent unstable angina reduced by 29%; p=0.02.

No significant reductions in death from any cause; of death or MI; or stroke
Summary
Among patients who have recently had an acute coronary syndrome, an intensive lipid lowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.