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J Am Coll Cardiol, 2006; 48:438-445, doi:10.1016/j.jacc.2006.04.070
(Published online 11 July 2006). © 2006 by the American College of Cardiology Foundation |
Thrombolysis In Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.
Manuscript received January 23, 2006; revised manuscript received March 30, 2006, accepted April 4, 2006.
* Reprint requests and correspondence: Dr. Christopher P. Cannon, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115. (Email: cpcannon{at}partners.org).
OBJECTIVES: The purpose of this study was to conduct a meta-analysis that compares the reduction of cardiovascular outcomes with high-dose statin therapy versus standard dosing.
BACKGROUND: Debate exists regarding the merit of more intensive lipid lowering with high-dose statin therapy as compared with standard-dose therapy.
METHODS: We searched PubMed and article references for randomized controlled trials of intensive versus standard-dose statin therapy enrolling more than 1,000 patients with either stable coronary heart disease or acute coronary syndromes. Four trials were identified: the TNT (Treating to New Targets) and the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid-Lowering) trials involved patients with stable cardiovascular disease, and the PROVE IT–TIMI-22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction-22) and A-to-Z (Aggrastat-to-Zocor) trials involved patients with acute coronary syndromes. We carried out a meta-analysis of the relative odds on the basis of a fixed-effects model using the Mantel-Haenszel method for the major outcomes of death and cardiovascular events.
RESULTS: A total of 27,548 patients were enrolled in the 4 large trials. The combined analysis yielded a significant 16% odds reduction in coronary death or myocardial infarction (p < 0.00001), as well as a significant 16% odds reduction of coronary death or any cardiovascular event (p < 0.00001). No difference was observed in total or non-cardiovascular mortality, but a trend toward decreased cardiovascular mortality (odds reduction 12%, p = 0.054) was observed.
CONCLUSIONS: Intensive lipid lowering with high-dose statin therapy provides a significant benefit over standard-dose therapy for preventing predominantly non-fatal cardiovascular events.
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