The PROVE IT-TIMI 22 study
Comparison of Intensive and Moderate Lipid Lowering with Statins after Acute Coronary Syndromes The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) study

Background

• Lipid-lowering therapy with statins reduces risk of CV events across a wide range of cholesterol levels Current guidelines recommend a target LDL < 100 mg/dl in patients with established coronary artery disease or diabetes
• It is not clear whether lowering lipid levels further would increase the clinical benefit

Aim

To compare the standard degree of LDL cholesterol lowering to approximately 100 mg/dl with the use of 40 mg pravastatin daily, with more intensive LDL cholesterol lowering to approximately 70 mg/dl with the use of 80 mg atorvastatin daily as a means of preventing death or major CV events in patients with an acute coronary syndrome (ACS)

Patient Number

4162

Patient characteristics

• Patients who had been hospitalized for an ACS (either acute MI or high-risk unstable angina) in the preceding 10 days

  Patients in a stable condition

  Total cholesterol < 240 mg/dl (measured within the first 24 hours after the onset of ACS or up to 6 months earlier if no sample was obtained during first 24 hours) in patients not receiving long-term lipid lowering therapy at the time of their index ACS

• Total cholesterol < 200 mg/dl in patients receiving long-term lipid lowering therapy

Study regimens

Atorvastatin 80 mg vs Pravastatin 40 mg

Mean follow-up

24 months

Results

• Median LDL achieved was 95 mg/dl in the pravastatin group and 62 mg/dl in the atorvastatin group.

• Among 2985 patients (75%) who had not previously received statin therapy, the median LDL levels had fallen by 22% at 30 days in the pravastatin group and by 51% in the atorvastatin group (p < 0.001)

  Among the 990 patients who had previously received statin therapy (25%), LDL levels were essentially unchanged in the pravastatin group, whereas they fell by an additional 32% in the atorvastatin group

  Median HDL levels rose by 8.1% in the pravastatin group and 6.5% in the atorvastatin group

• Atorvastatin demonstrated a 16% reduction in the primary end point (composite of death from any cause, MI, documented unstable angina requiring rehospitalization, revascularisation with either PTCA or CABG, and stroke) as compared to pravastatin.

• Benefit of high-dose atorvastatin as compared with standard-dose pravastatin emerged as early as 30 days and was consistent over time.

• Risk of secondary endpoint (death due to CHD , MI or revascularisation) as well as individual components of primary endpoint was lesser in the atorvastatin group, as compared to pravastatin.

• Atorvastatin high-dose therapy was well tolerated

Conclusion

• Among patients who have recently had an ACS, intensive lipid lowering with atorvastatin provides greater protection against death or major CV events than does a standard statin regimen

• Such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels

“The extent of the benefit afforded by the 80 mg dose of atorvastatin is in keeping with what would be expected on the basis of the greater degree of lipid lowering produced by this regimen.”

“However, we cannot exclude the possibility that the difference in clinical outcomes may be due in part to non-lipid-related pleiotropic effects, which may differ between the two statins.”

N Engl J Med April 8, 2004

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