title: Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial.
abstract: OBJECTIVE
  Our objective was to determine the timing of benefit with intensive statin therapy after an acute coronary syndrome (ACS) in two time windows: an early window soon after an ACS and a late window in more stable patients.
  
  
  BACKGROUND
  The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial showed that the use of intensive statin therapy improved clinical outcomes over two years in ACS patients versus standard therapy. The relative contributions of early or late effects to the overall clinical efficacy of intensive therapy are presently unclear.
  
  
  METHODS
  A total of 4,162 patients with ACS were recruited in the PROVE IT-TIMI 22 trial. Patients were randomized to intensive statin therapy (atorvastatin, 80 mg) or standard therapy (pravastatin, 40 mg). The composite triple end point of death, MI, or rehospitalization for recurrent ACS was determined in each group at 30 days. The composite triple and primary end points were assessed in stable patients from six months to the end of study, after censoring for clinical events before six months.
  
  
  RESULTS
  The composite end point at 30 days occurred in 3.0% of patients receiving atorvastatin 80 mg versus 4.2% of patients receiving pravastatin 40 mg (hazard ratio [HR] = 0.72; 95% confidence interval [CI], 0.52 to 0.99; p = 0.046). In stable patients, atorvastatin 80 mg was associated with a composite event rate of 9.6% versus 13.1% in the pravastatin 40 mg group (HR = 0.72; 95% CI, 0.58 to 0.89; p = 0.003).
  
  
  CONCLUSIONS
  Intensive statin therapy early after ACS leads to a reduction in clinical events at 30 days, consistent with greater early pleiotropic effects. In stable patients, intensive statin therapy provides long-term reduction in clinical events when compared with standard therapy. Thus, ACS patients should be started in-hospital and continued long-term on intensive statin therapy.
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Carolyn H
authors.initials: CH
authors.lastname: McCabe
authors.forename: Richard
authors.initials: R
authors.lastname: Cairns
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tonkin
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
authors.forename: Graham
authors.initials: G
authors.lastname: Jackson
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000208:Acute Disease; D000789:Angina, Unstable / Q000188:drug therapy*; D000069059:Atorvastatin; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D017035:Pravastatin / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D013577:Syndrome; D013997:Time Factors
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D017035:Pravastatin