Reduction in recurrent cardiovascular events with intensive lipid-lowering statin therapy compared with moderate lipid-lowering statin therapy after acute coronary syndromes from the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) trial.
OBJECTIVE
In addition to reducing first events in patients after an acute coronary syndrome (ACS), we hypothesized that high-dose atorvastatin 80 mg would also reduce recurrent cardiovascular events, and therefore total events, compared with pravastatin 40 mg during the 2-year follow-up.


BACKGROUND
In the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) trial, more intensive lipid lowering with high-dose atorvastatin reduced the first occurrence of the primary end point (death, myocardial infarction, unstable angina requiring rehospitalization, stroke, or revascularization > or = 30 days) compared with moderate lipid lowering with pravastatin.


METHODS
Poisson regression analysis was performed to compare the number of occurrences of the primary end point between high-dose atorvastatin and pravastatin in the PROVE IT-TIMI 22 trial.


RESULTS
As previously reported, first primary end point events were reduced by 16% with atorvastatin 80 mg versus pravastatin 40 mg (n = 464 vs. n = 537, respectively; p = 0.005). Additional events were also reduced by 19% with atorvastatin 80 mg (n = 275 vs. n = 340, respectively; p = 0.009). Overall, there were 138 fewer primary efficacy events with atorvastatin 80 mg versus pravastatin 40 mg (n = 739 vs. n = 877, respectively; rate ratio: 0.85, 95% confidence interval: 0.77 to 0.94, p = 0.001).


CONCLUSIONS
Although analytic techniques commonly used in clinical outcomes trials censor patients who experience a component of the primary composite end point, total cardiovascular events are important to patients, clinicians, and health care payers. Maintaining low levels of low-density lipoprotein cholesterol is central to preventing additional atherosclerotic development and subsequent cardiovascular events. Atorvastatin 80 mg, a more intensive low-density lipoprotein cholesterol lowering agent, reduced both first and subsequent primary end point events compared with pravastatin 40 mg after ACS.
Murphy
Sabina A
SA
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Cannon
Christopher P
CP
Wiviott
Stephen D
SD
McCabe
Carolyn H
CH
Braunwald
Eugene
E
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D000789:Angina, Unstable / Q000517:prevention & control; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D017035:Pravastatin / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D012044:Regression Analysis; D055502:Secondary Prevention; D020521:Stroke / Q000517:prevention & control
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002097:C-Reactive Protein; D002784:Cholesterol; D000069059:Atorvastatin; D017035:Pravastatin