FOCUS ISSUE: PROVE IT-TIMI 22
Early and Late Benefits of High-Dose Atorvastatin in Patients With Acute Coronary Syndromes
Results From the PROVE IT-TIMI 22 Trial
Kausik K. Ray, MRCP, MD*,
Christopher P. Cannon, MD, FACC*,*,
Carolyn H. McCabe, BS*,
Richard Cairns, BSc ,
Andrew M. Tonkin, MD ,
Frank M. Sacks, MD ,
Graham Jackson, MD, FRCP||,
Eugene Braunwald, MD, MACC* for the PROVE IT-TIMI 22 Investigators
* TIMI Study Group, Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts
Nottingham Clinical Research Group, Nottingham, United Kingdom
Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia
Harvard School of Public Health, Boston, Massachusetts
|| Guy’s Hospital, London, England
Manuscript received January 3, 2005;
revised manuscript received March 18, 2005,
accepted March 22, 2005.
* Reprint requests and correspondence: Dr. Christopher P. Cannon, TIMI Study Group, 350 Longwood Avenue, 1st Floor, Boston, Massachusetts 02115 (Email: cpcannon{at}partners.org).
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | ACS = acute coronary syndrome | | CI = confidence interval | | CRP = C-reactive protein | | HR = hazard ratio | | LDL-C = low-density lipoprotein cholesterol | | MI = myocardial infarction | | PROVE IT-TIMI 22 = Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22 | | TNT = Treating to New Targets study |
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