Effect of Lowering LDL Cholesterol Substantially Below Currently Recommended Levels in Patients With Coronary Heart Disease and Diabetes

Abstract

OBJECTIVE -The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes.RESEARCH DESIGN AND METHODS -A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of Ͻ130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 (n ϭ 753) or 80 (n ϭ 748) mg/day. Patients were followed for a median of 4.9 years. The primary end point was the time to first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke.RESULTS -End-of-treatment mean LDL cholesterol levels were 98.6 mg/dl with atorvastatin 10 mg and 77.0 mg/dl with atorvastatin 80 mg. A primary event occurred in 135 patients (17.9%) receiving atorvastatin 10 mg, compared with 103 patients (13.8%) receiving atorvastatin 80 mg (hazard ratio 0.75 [95% CI 0.58 -0.97], P ϭ 0.026). Significant differences between the groups in favor of atorvastatin 80 mg were also observed for time to cerebrovascular event (0.69 [0.48 -0.98], P ϭ 0.037) and any cardiovascular event (0.85 [0.73-1.00], P ϭ 0.044). There were no significant differences between the treatment groups in the rates of treatmentrelated adverse events and persistent elevations in liver enzymes.CONCLUSIONS -Among patients with clinically evident CHD and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25% compared with atorvastatin 10 mg.

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