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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Meta-Analysis of Cardiovascular Outcomes Trials Comparing Intensive Versus Moderate Statin Therapy

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.

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

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