Clinical Research
Coronary Artery Disease
Meta-Analysis of Cardiovascular Outcomes Trials Comparing Intensive Versus Moderate Statin Therapy

https://doi.org/10.1016/j.jacc.2006.04.070Get rights and content
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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.

Abbreviations and Acronyms

A-to-Z
Aggrastat-to-Zocor trial
ACS
acute coronary syndrome
CI
confidence interval
CTT
Cholesterol Treatment Trialists
IDEAL
Incremental Decrease in End Points Through Aggressive Lipid-Lowering trial
LDL
low-density lipoprotein
MI
myocardial infarction
NCEP
National Cholesterol Education Program
OR
odds ratio
PROVE IT–TIMI-22
Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction-22 trial
TNT
Treating to New Targets trial

Cited by (0)

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.