Author + information
- Received January 23, 2006
- Revision received March 30, 2006
- Accepted April 4, 2006
- Published online August 1, 2006.
- Christopher P. Cannon, MD⁎ (, )
- Benjamin A. Steinberg, BA,
- Sabina A. Murphy, MPH,
- Jessica L. Mega, MD and
- Eugene Braunwald, MD
- ↵⁎Reprint requests and correspondence:
Dr. Christopher P. Cannon, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
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.
The PROVE IT–TIMI-22 trial was sponsored by Bristol-Myers Squibb and Sankyo Co. LTD, and the A-to-Z trial was sponsored by Merck. Dr. Cannon currently receives research grant support from Merck, AstraZeneca, and Schering-Plough, and serves on advisory boards and/or is a consultant to AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Schering-Plough, Pfizer, and Sanofi-Aventis. Mr. Steinberg is a research fellow supported by The Stanley J. Sarnoff Endowment for Cardiovascular Science, Inc., Great Falls, Virginia. Dr. Braunwald receives research grant support from Bristol-Myers Squibb, Merck, Pfizer, and Schering-Plough.
- Received January 23, 2006.
- Revision received March 30, 2006.
- Accepted April 4, 2006.
- American College of Cardiology Foundation