Effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels - Effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels

Description:

The goal of the trial was to assess the efficacy and safety of rosuvastatin and extended-release (ER) niacin alone and in combination in patients with combined hyperlipidemia and low high-density lipoprotein (HDL) cholesterol levels.

Study Design

Study Design:

Patients Screened: 774
Patients Enrolled: 270
Mean Follow Up: 24 weeks
Female: 28%

Patient Populations:

Age ≥18 years; dyslipidemia (Fredrickson's type IIb or IV hyperlipidemia); fasting total cholesterol levels ≥200 mg/dl; fasting triglycerides 200-800 mg/dl; apolipoprotein B ≥110 mg/dl; and HDL cholesterol <45 mg/dl

Exclusions:

Pregnant or lactating women; active liver disease or hepatic dysfunction; active arterial disease within past three months; uncontrolled hypertension or hypothyroidism; serum creatine kinase concentrations >3 times the upper limit of normal; serum creatinine concentrations >1.8 mg/dl; and the use of concomitant medications known to affect serum lipid levels or present potential safety concerns

Primary Endpoints:

Percent change from baseline in fasting plasma LDL cholesterol levels at 24 weeks

Secondary Endpoints:

Percent change in fasting plasma levels of total cholesterol, non-HDL cholesterol (total cholesterol minus HDL cholesterol), triglycerides, very–low-density lipoprotein cholesterol, apolipoprotein B, HDL cholesterol, apolipoprotein A-I, and lipoprotein(a), all at 24 weeks

Drug/Procedures Used:

Following a dietary lead-in period, patients were randomized open-label in a 2:3:3:3 ratio to rosuvastatin monotherapy (n=46), ER niacin monotherapy (n=72), rosuvastatin 40 mg/ER niacin 1 g (n=72), or rosuvastatin 10 mg/ER niacin 2 g (n=80). All other lipid-lowering medications were discontinued.

Principal Findings:

Low-density lipoprotein (LDL) cholesterol was reduced by 48% in the rosuvastatin monotherapy arm, significantly more than either ER niacin 2 g (-0.1%, p<0.001) or rosuvastatin 10 mg/ER niacin 2 g (-36%, p<0.01), but did not differ from rosuvastatin 10 mg/ER niacin 1 g (-42%, p=NS). Similar results were observed in non-HDL cholesterol (-49% vs. -11%, p<0.001; -38%, p<0.01; and -47%, p=NS, respectively) and total cholesterol (-41% vs. -7%, p<0.001; -28%, p<0.001; and -38%, p=NS, respectively). There was no significant difference by treatment group in triglyceride reductions (-33% vs. -21%, -34%, and -39%, respectively).

Compared with rosuvastatin alone, rosuvastatin 10 mg/ER niacin 2 g was associated with significantly larger increases in HDL cholesterol (11% vs. 24%, p<0.001) and apolipoprotein A-I (5% vs. 11%, p<0.01), but there were no significant differences between the monotherapy groups (11% vs. 12% for HDL; 5% vs. 7% for apolipoprotein A-I).

Adverse events occurred in 74% of patients in the rosuvastatin monotherapy arm, 90% in the ER niacin monotherapy arm, and 85% in the groups receiving combination therapy. There were no treatment-related serious adverse events in any arm.

Interpretation:

Among patients with combined hyperlipidemia and low HDL cholesterol levels, treatment with rosuvastatin monotherapy was associated with larger reductions in LDL and total cholesterol than niacin alone or rosuvastatin in combination with ER niacin 2 g, but did not differ from rosuvastatin in combination with ER niacin 1 g.

The finding that ER niacin alone did not reduce LDL cholesterol levels from baseline was unlike results observed by Morgan et al. in an earlier trial of ER niacin, which showed a 6% and 15% reduction in LDL for 1 g and 2 g doses, respectively, in patients with primary hypercholesterolemia, but not unlike results from studies by Guyton et al. and Grundy et al., which showed no significant effect on LDL.

References:

Capuzzi DM, Morgan JM, Weiss RJ, Chitra RR, Hutchinson HG, Cressman MD. Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels. Am J Cardiol 2003;91:1304-10.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet

Keywords: Fluorobenzenes, Cholesterol, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Apolipoprotein A-I, Pyrimidines, Niacin, Hypercholesterolemia, Triglycerides, Fasting, Sulfonamides


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