Higher-dose atorvastatin best for patients with diabetes

Risk of a coronary event was 25% lower among patients assigned 80 mg of atorvastatin than in those assigned the 10-mg regimen.

Patients with diabetes who are at the highest risk for cardiovascular disease may benefit from more aggressive statin treatment, according to new results from the Treating to New Targets trial.

The results, presented at the 65th Annual Scientific Sessions of the American Diabetes Association, demonstrated that patients with diabetes and heart disease who were treated with atorvastatin (Lipitor, Pfizer) at a dose of 80 mg had greater reductions of LDL cholesterol than similar patients treated with atorvastatin at a dose of 10 mg.

The study was presented by James Shepherd, MD, from the department of pathological biochemistry at the University of Glasgow Medical School in Scotland.

TNT trial

The study was part of the Treating to New Targets (TNT) trial, which examined treatments for vascular risk reduction in patients with a history of CHD. TNT involved 10,000 people in 14 countries aged 35 to 75.

This arm of the TNT trial examined 1,500 patients with both heart disease and diabetes.

Patients with diabetes were randomly assigned one of two regimens of atorvastatin treatment. The first group was assigned 10 mg daily; the second was assigned 80 mg daily. The baseline cholesterol level was 155 mg/dL in both groups, which were also matched for age and gender.

The follow-up period was an average of 4.9 years. By the end of this period, the average LDL cholesterol levels were 99 mg/dL among patients in the 10-mg group and 77 mg/dL among patients in the 80-mg group. Both treatments were associated with reduced LDL cholesterol that was below the National Cholesterol Education Program recommended target level of <100 mg/dL.

By the end of the follow-up period, patients in the 80-mg group showed more significant reductions in CVD risk than patients in the 10-mg group. Compared with the 10-mg regimen, the 80-mg regimen was associated with fewer cardiovascular events, including CHD death, nonfatal MI, resuscitated cardiac arrest and both fatal and nonfatal stroke.

Risk reduction

According to Shepherd, the risk of a major cardiovascular event was 25% lower among patients treated with the 80-mg regimen. By the end of the follow-up period, 17.9% of patients in the 10-mg group and 13.8% of patients in the 80-mg group had experienced at least one cardiovascular event.

Shepherd noted that the risk of cerebrovascular event was significantly lower among patients in the 80-mg group. Seventy-five patients in the 10-mg group and 52 patients in the 80-mg group had a stroke during the follow-up period.

The two treatments were associated with similar safety profiles. Shepherd said both the musculoskeletal safety profile and the incidence of repeat liver enzyme elevations were similar in the two groups and were within product labeling.

Patients with diabetes

The more aggressive dose of 80 mg of atorvastatin would be particularly beneficial for patients with diabetes and CHD. “Patients with diabetes and heart disease are at the highest level of risk for CVD,” Shepherd told Cardiology Today. “Doctors should be aggressive with these patients.”

The added presence of diabetes among patients with CHD represents a significant increase in the risk for a coronary event. Shepherd said that in this study, patients who had diabetes in addition to a history of CHD were 25% more likely to have a coronary event during the follow-up period than patients with CHD alone.

Furthermore, patients with diabetes had twice as many strokes and were two to three times more likely to be hospitalized for congestive heart failure.

Shepherd said he recommends doctors aggressively treat high-risk patients to help them achieve their target levels for LDL cholesterol. “I recommend that doctors treat patients according to their risks,” Shepherd said. “Lowering LDL below target levels has a greater benefit, and doctors should push patients to achieve this level. This is particularly important for those patients at the highest level of risk.” – by Jay Lewis

For more information:

• Shepherd J. Intensive lipid lowering with atorvastatin in patients with diabetes and stable coronary disease. Presented at the 65th Annual Scientific Sessions of the American Diabetes Association. June 10-14, 2005. San Diego.