Comparison of extended-release niacin and atorvastatin monotherapies and combination treatment of the atherogenic lipid profile in diabetes mellitus

Abstract

• • • Fifty-three diabetic patients with either separate or combined abnormalities of the atherogenic lipid profile, defined by low-density lipoprotein (LDL) peak particle diameter 263 A and/or high-density lipoprotein (HDL) fraction-2 40% were recruited from the Diabetes Research Center. All subjects signed informed consent. This open-label, uncontrolled dosing and efficacy study used retrospective chart review analyses after aggressive antilipid treatment as previously reported in detail. The mean extended-release niacin dose was 2,819 821 mg/day, and atorvastatin was used at 80 mg/day. No patients received fibrates, bile acids, or thiazolidinediones during the observation period. Routine lipid, gel electrophoresis measurements of LDL and HDL species and hemoglobin A1c were performed as previously described in detail before and after 6 weeks of stable dosing. All data are presented as mean 1 SD. Paired and unpaired t tests were used to compare preand post-treatment results and differences between treatment groups, respectively. Table 1 shows the preand post-treatment results for the 3 treatment groups. To compare the 3 treatments, post-treatment lipid values were evaluated (Table 1). All pretreatment comparisons were similar among the groups (p NS), except where indicated. For subjects with abnormal LDL size, a combination therapy of atorvastatin and niaspan tended to be more effective than niaspan (p 0.08) or atorvastatin (p 0.05) monotherapy in lowering mean triglyceride values. Because of substantial baseline differences, an evaluation of the preand post-treatment changes showed combination treatment to be more effective than niaspan monotherapy for triglyceride lowering when percentage change (p 0.002) or delta change (p 0.05) was used. Atorvastatin monotherapy and the combination treatment reduced mean total LDL cholesterol levels substantially more than niaspan monotherapy (p 0.0001 and p 0.0002, respectively). Niaspan monotherapy increased mean LDL size more effectively than atorvastatin monotherapy (p 0.05), and combination treatment further improved size from atorvastatin monotherapy (p 0.03), but not niaspan monotherapy (p NS). Combination treatment reduced mean small, dense LDL cholesterol mass more effectively than niaspan monotherapy (p 0.001), and there was also a trend for atorvastatin monotherapy to be more effective than niaspan (p 0.07). The latter trend remained when preand post-treatment percentage changes were compared (p 0.04). Although mean levels of small, dense LDL cholesterol mass were not statistically different in the atorvastatin monotherapy group versus the combination treatment group because of baseline differences, preand post-treatment percentage change (p 0.05) and delta change (p 0.02) comparisons showed combination treatment to be more effective than atorvastatin monotherapy. Among patients with HDL-2 40%, combination therapy was more effective than atorvastatin monotherapy in reducing mean triglyceride levels (p 0.05). Combination therapy was also more effective than niaspan monotherapy in triglyceride lowering as shown by percentage change (p 0.003). Combination treatment was more effective than atorvastatin monotherapy in improving total HDL cholesterol values as shown by preand post-treatment percentage changes (p 0.001) and delta changes (p 0.002). Combination treatment was also more effective than atorvastatin in increasing HDL-2 cholesterol mass when comparing percentage changes (p 0.04) and delta changes (p 0.04). Niaspan monotherapy increased mean total HDL cholesterol (p 0.005) and HDL-2 cholesterol mass (p 0.03) more effectively than atorvastatin. HDL-2 levels across treatments were not statistically different for mean, percentage, or delta changes. Atorvastatin did not effectively treat lipoprotein(a) (Lp(a)) abnormalities (Lp(a) 25 mg/ dl) with mean preand post-treatment levels of 45 21 versus 44 6 mg/dl (n 4, p NS), whereas niaspan and combination decreased mean Lp(a) levels from 37 10 to 23 10 mg/dl (n 12, p 0.01) and from 54 19 to 35 6 mg/dl, respectively (n 4, p 0.06).