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

Meta-Analysis of Cardiovascular Outcomes Trials Comparing Intensive Versus Moderate Statin Therapy Christopher P. Cannon, Benjamin A. Steinberg, Sabina A. Murphy, Jessica L. Mega, Eugene Braunwald We conducted a meta-analysis of large, randomized controlled trials of intensive versus standard-dose statin therapy with either stable coronary heart disease or acute coronary syndromes. The trials analyzed included TNT (Treating to New Targets), IDEAL (Incremental Decrease in End Points Through Aggressive Lipid-Lowering), PROVE IT–TIMI-22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction-22) and A-to-Z (Aggrastat-to-Zocor). The analysis of 27,548 patients yielded a 16% odds reduction in coronary death or myocardial infarction (p < 0.00001) and a 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 was observed. Thus, intensive lipid lowering with high-dose statin therapy provides a significant benefit over standard-dose therapy for preventing predominantly non-fatal cardiovascular events. 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. Debate exists regarding the merit of more intensive lipid lowering with high-dose statin therapy as compared with standard-dose therapy. 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. 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 i