Elevated atorvastatin dosage reduces rate of cardiovascular events in CHD patients

Intensive therapy with atorvastatin 80 mg/d, in comparison with the same medication at 10 mg/d, significantly reduced the rate of major cardiovascular events by 25% in patients with clinically evident stable coronary heart disease (CHD) and diabetes, according to a study published in Diabetes Care.

The results supported the increasingly popular claim that lowering LDL cholesterol to values well below currently recommended levels with more intensive statin therapy is associated with additional cardiovascular benefit.

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. There was little change in HDL cholesterol in either treatment group over the course of the study.

A primary event occurred in 135 patients (17.9%) receiving atorvastatin 10 mg, compared with 103 patients (13.8%) receiving atorvastatin 80 mg (HR= 0.75; 95% CI, 0.58–0.97; P=.026).

Significant differences between the groups in favor of atorvastatin 80 mg were also observed for time to cerebrovascular event (HR=0.69; 95% CI, 0.48–0.98; P=.037) and any cardiovascular event (HR=0.85; 95% CI, 0.73–1.00; P=.044). There was no significant difference between the treatments for all-cause mortality.

An additional benefit from atorvastatin 80 mg was a reduced incidence of first stroke compared with those in the atorvastatin 10 mg group. Patients with and without good glycemic control randomized to atorvastatin 80 mg experienced a lower incidence of first major cardiovascular event, coronary event, stroke, nonfatal nonprocedure-related myocardial infarction, and CHD death than patients randomized to atorvastatin 10 mg, with a significant reduction in risk for major cardiovascular events in patients with hemoglobin A_1c (HbA_1c)≤7%.

There were no significant differences between the treatment groups in the rates of treatment-related adverse events and persistent elevations in liver enzymes.

"Pending a definitive trial, these data suggest that the use of high-dose statin to achieve an LDL cholesterol level considerably <100 mg/dL may be appropriate for patients with diabetes and CHD, irrespective of their initial LDL cholesterol level, age, duration of diabetes, or glycemic control," the study's authors stated.

The American Diabetes Association (ADA), in a 2005 update of its clinical practice recommendations for patients with diabetes and cardiovascular disease, advised that use of a high-dose statin to achieve an LDL cholesterol level of <70 mg/dL was a therapeutic option in diabetic patients with cardiovascular disease.

The subanalysis of diabetic patients in the TNT study upheld the ADA's recommendation by: confirming the high cardiovascular event rate in CHD patients who also have diabetes; providing direct evidence of cardiovascular risk reduction with high-dose statin therapy in this population; and demonstrating that this risk reduction is independent of baseline LDL cholesterol.

SOURCE Shepherd J, Barter P, Carmena R, et al, for the Treating to New Targets Investigators. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care. 2006;29:1220–1226.