Intense statin therapy treats atheromas in diabetes

SAN FRANCISCO – Atheromas regressed to similar degrees in patients with or without diabetes on high-intensity statin therapy for symptomatic coronary artery disease, a post hoc subgroup analysis of 1,039 patients found.

The primary endpoint, percent atheroma volume (PAV), decreased by a mean of 1.04% in 159 diabetic patients and by 1.21% in 880 nondiabetic patients compared with baseline – significant drops in both groups, Dr. Brian Stegman and his associates reported. PAV is the percentage of a single vessel’s volume occupied by atheroma.

The total atheroma volume (TAV), a secondary endpoint, decreased compared with baseline by 5.62 mm³ in the diabetic group and by 7.29 mm³ in the nondiabetic group, both of which also were significant changes, he said at the annual meeting of the American College of Cardiology.

Data came from the SATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin) trial, which compared intensive therapy with one of the two statin drugs in patients who underwent serial intravascular ultrasonography to assess disease regression. Patients were treated with either 40 mg/day rosuvastatin or 80 mg/day atorvastatin for 2 years. The two drug groups showed similar reductions in PAV, with a greater reduction in TAV using rosuvastatin (N. Engl. J. Med. 2011;365:2078-87).

Previous studies using have shown that aggressive reductions in LDL levels lead to significant regression in coronary atheromas as measured by intravascular ultrasound, but it has not been clear whether this is true in patients with diabetes as well as those without, said Dr. Stegman of the Cleveland Clinic Foundation.

The current analysis regrouped the SATURN cohort by diabetes status. High-intensity statin therapy produced substantial reductions in LDL in both groups, to a similar degree: a 52-mg/dL drop in diabetics and a 55-mg/dL decrease in nondiabetics. HDL levels increased by 3 mg/dL in diabetics and 5 mg/dL in nondiabetics, a significant difference between groups. Total cholesterol decreased 52 mg/dL in diabetics and 54 mg/dL in nondiabetics, and triglyceride levels decreased 13 mg/dL in diabetics and 12 mg/dL in nondiabetics, measures that were not significantly different between groups.

In both diabetics and nondiabetics, the lower the LDL on treatment, the greater the regression of atheroma, according to a linear regression model constructed by the investigators.

The changes in PAV and TAV in both groups showed that "with high-intensity statin therapy, we saw equal regression of atheroma in diabetics compared with nondiabetics," Dr. Stegman said. Lumen volumes were preserved over the 2-year period to a similar degree in both groups, as measured by change in lumen volume and external elastic membrane volume.

The findings differ from previous results in a pooled analysis of five trials involving intravascular ultrasound measurements of atherosclerosis progression in 2,237 patients, 416 of whom had diabetes, he noted. In that analysis, PAV increased by 0.05% in diabetics and by 0.6% in nondiabetics, compared with decreases of 1.21% and 1.04%, respectively, in the current analysis. *The TAV decreased by 2.7 mm³ in diabetics and 0.6 mm³ in nondiabetics, much less than the 5.62-mm³ and 7.29-mm³decreases, respectively, in the current analysis (J. Am. Coll. Cardiol. 2008;52:255-62).

The different outcomes in the two analyses may be due to less aggressive treatment in the trials pooled in the 2008 analysis, which did not decrease LDL levels as much as the high-intensity regimens in the SATURN trial. "I think our current study indicates that diabetic patients require fairly aggressive lipid therapy to get the same results as in nondiabetic patients," Dr. Stegman said.

Separate, previous trials using intravascular ultrasound have shown that high-dose statin therapy is more effective than moderate- or low dose regimens to halt progression of atherosclerosis, he added.

The analysis is limited by its post hoc nature, differing patient numbers in each group, and differences in baseline characteristics. Patients in the diabetic group were significantly older, with a higher mean body mass index, and more likely to be female and to have a history of hypertension compared with nondiabetics. Baseline lipid levels were significantly different between groups, with lower total cholesterol, LDL, and HDL levels and higher triglyceride levels in patients with diabetes. Intravascular ultrasound measurements also differed significantly, with greater PAV and TAV in the diabetic group.

The PAV and TAV endpoints were surrogate measures of clinical outcomes, another limitation of the analysis, but previous studies with intravascular ultrasound have reported that greater PAV and greater progression of PAV are associated with an increased risk of major adverse cardiovascular events, he said.

Dr. Stegman reported having no relevant financial disclosures. Some of his associates in the study reported financial associations with multiple pharmaceutical companies, several of which market statins.