Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy.
OBJECTIVE
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.
Cannon
Christopher P
CP
Thrombolysis In Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. cpcannon@partners.org
Steinberg
Benjamin A
BA
Murphy
Sabina A
SA
Mega
Jessica L
JL
Braunwald
Eugene
E
D002318:Cardiovascular Diseases / Q000517:prevention & control; D003327:Coronary Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013577:Syndrome; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors