Extended-release niacin/laropiprant lipid-altering consistency across patient subgroups.

BACKGROUND: In patients with primary hypercholesterolemia or mixed dyslipidemia, extended-release niacin/laropiprant (ERN/LRPT) improves key lipid parameters associated with increased atherosclerotic coronary heart disease (CHD) risk. AIM: This analysis examined data from four Phase III, randomised, double-blind trials to determine the consistency of ERN/LRPT's lipid-altering efficacy among subgroups of patients. METHODS: Data from four Phase III, randomised, double-blind trials of ERN/LRPT were analysed to determine the consistency of ERN/LRPT's lipid-altering efficacy among subgroups of gender, race (white, non-white), region (US, ex-US), baseline age (<65, ≥65 years), use of statin therapy, CHD risk status (low, multiple, high) and type of hyperlipidemia (primary hypercholesterolemia, mixed dyslipidemia), as well as across baseline low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels. End-points included the per cent change from baseline in LDL-C, HDL-C and TG levels. Consistency of the treatment effects on LDL-C, HDL-C and TG across subgroups was evaluated by examining treatment difference estimates with 95% confidence intervals. RESULTS: Treatment with ERN/LRPT significantly improved LDL-C, HDL-C and TG levels compared with placebo/active comparator in each study cohort. These effects were generally consistent across all examined subgroups. CONCLUSION: Extended-release niacin/laropiprant represents an effective therapeutic option for the treatment of dyslipidemia across a range of patient types.

Efficacy and safety of extended-release niacin/laropiprant plus statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia.

BACKGROUND: Co-administration of niacin with statin offers the potential for additional lipid management and cardiovascular risk reduction. However, niacin is underutilised because of the side effects of flushing, mediated primarily by prostaglandin D(2) (PGD(2)). A combination tablet containing extended-release niacin and laropiprant (ERN/LRPT), a PGD(2) receptor (DP1) antagonist, offers improved tolerability. This study assessed the efficacy and safety of ERN/LRPT added to statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia who were not at their National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol (LDL-C) goal based on their coronary heart disease risk category (high, moderate or low). METHODS: After a 2- to 6-week run-in statin (simvastatin 10 or 20 mg or atorvastatin 10 mg) period, 1216 patients were randomised equally to one of two treatment groups in a double-blind fashion: group 1 received ERN/LRPT (1 g) plus the run-in statin dose and advanced to ERN/LRPT (2 g) after 4 weeks for an additional 8 weeks, with no adjustments to the run-in statin dose; group 2 received simvastatin or atorvastatin at twice their run-in statin dose and remained on this stable dose for 12 weeks. RESULTS: ERN/LRPT added to statin (pooled across statin and statin dose) significantly improved key lipid parameters vs. the doubled statin dose (pooled): the between-treatment group difference in least squares mean per cent change [95% confidence interval (CI)] from baseline to week 12 in LDL-C (primary end-point) was -4.5% (-7.7, -1.3) and in high-density lipoprotein cholesterol (HDL-C) was 15.6% (13.4, 17.9) and in median per cent change for triglyceride (TG) was -15.4% (-19.2, -11.7). Treatment-related adverse experiences (AEs) related to flushing, pruritis, rash, gastrointestinal upset and elevations in liver transaminases and fasting serum glucose occurred more frequently with ERN/LRPT added to statin vs. statin dose doubled. CONCLUSIONS: The addition of ERN/LRPT to ongoing statin treatment produced significantly improved lipid-modifying benefits on LDL-C, HDL-C and TG and all other lipid parameters compared with doubling the statin dose in patients with primary hypercholesterolaemia or mixed dyslipidaemia. The types of AEs that occurred at a greater frequency in the ERN/LRPT group were those typically associated with niacin.

Safety and efficacy of ezetimibe monotherapy in 1624 primary hypercholesterolaemic patients for up to 2 years.

AIMS: This report examined the safety and efficacy of treatment for up to 2 years with the cholesterol absorption inhibitor, ezetimibe (EZE). METHODS: Two identical, randomised, double-blind trials (starting with 827 and 892 patients), evaluated the efficacy and safety of EZE 10 mg/day vs. placebo for 12 weeks in patients with primary hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) 3.3-5.1 mmol/l]. Upon completion of these base studies, patients were offered a 2-year, open-label extension study. Adverse event (AE) reports for EZE monotherapy-treated patients were summarised for 3-month intervals to allow for comparison with the placebo group of the 3-month base studies. The primary end-point for this analysis was the evaluation of the long-term safety and tolerability of EZE 10 mg monotherapy dosed daily for up to 24 months. RESULTS: The incidences of new AEs, treatment-related (TR) AEs, serious AEs (SAEs), TRSAEs and discontinuations as a result of AEs during any 3-month interval were comparable with the respective observations in the placebo group of the base studies. The incidences of AEs, TRAEs, SAEs, TRSAEs and discontinuations as a result of AEs decreased in almost every interval compared with earlier intervals throughout the 2-year study. In addition, the incidences of > or = 3-fold consecutive elevations of liver transaminases (0.7%) or > or = 10-fold increases in creatine phosphokinase (0.4%) for the entire 2-year treatment period were comparable with those of the placebo group (0.7% and 0.2% respectively). LDL-C reductions of approximately 18% were maintained throughout the study. CONCLUSIONS: Compared with placebo, treatment with EZE for up to 2 years in 1624 patients showed no evidence of increased incidence of AEs with increased treatment duration, while showing sustained effects on LDL-C reduction.

Efficacy and safety of ezetimibe 40 mg vs. ezetimibe 10 mg in the treatment of patients with homozygous sitosterolaemia.

OBJECTIVE: To assess the effect of ezetimibe (EZE) 40 mg/day on non-cholesterol sterol plasma concentrations in patients with homozygous sitosterolaemia (HoS). METHODS: This was a multi-centre, randomised, double-blind, placebo-controlled parallel group study. Twenty-seven patients (> or = 18 years) with HoS and plasma sitosterol levels > 5 mg/dl who had been taking EZE 10 mg/day for > or = 6 months prior to enrolment received open-label EZE 10 mg/day for the duration of the study and were randomised 1 : 1 to blinded EZE 30 mg/day (4 x EZE 10 mg tablets; n = 13) or placebo (1 x EZE 10 mg tablet and 3 x matching placebo tablets; n = 14) for 26 weeks. Patients were permitted to remain on other ongoing treatments (e.g. bile salt-binding resin, statin and/or low sterol diet). End-points included median per cent between-group changes from baseline in plasma sitosterol, campesterol, lathosterol, low-density lipoprotein (LDL) sterols, LDL cholesterol (LDL-C) measured by gas-liquid chromatography, and Achilles tendon thickness size measured radiographically. RESULTS: Ezetimibe 40 mg/day resulted in median per cent changes from baseline in plasma sitosterol levels of 3.3% vs. -10% in the EZE 10 mg/day group, in plasma campesterol of -0.5% vs. -9.7% in the EZE 10 mg/day group, and in plasma lathosterol of 0.8% vs. 1.1% in the EZE 10 mg/day group (p = ns for all between-group differences). Median per cent changes in the EZE 40 mg/day and EZE 10 mg/day groups, respectively, were 1.3% and 0% for LDL sterols and 2.5% and 4.4% for LDL-C (p = ns for both between-group differences). At study end-point, Achilles tendon thickness remained unchanged in the EZE 40 mg/day group and increased slightly in the EZE 10 mg/day group (2.2%), yielding a non-significant between-group difference of -2.2%. EZE 40 mg/day was generally well tolerated. CONCLUSIONS: In patients with HoS, treatment with EZE 40 mg/day for 26 weeks was no more effective at reducing plasma plant sterol concentrations vs. EZE 10 mg/day. EZE 40 mg/day had a safety and tolerability profile similar to EZE 10 mg/day.

Efficacy of ezetimibe/simvastatin 10/20 and 10/40 mg compared with atorvastatin 20 mg in patients with type 2 diabetes mellitus.

AIM: This randomized, double-blind study evaluated the efficacy of switching from atorvastatin (ATV) 10 mg to ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg, EZE/SIMVA 10/40 mg or doubling the dose of ATV from 10 to 20 mg in patients with type 2 diabetes (T2D). METHODS: Eligible patients had haemoglobin A(1C)< or =10%, were aged > or =18 years and were on ATV 10 mg for > or =6 weeks before study entry. After a 4-week open-label ATV 10 mg run-in, patients were randomized to EZE/SIMVA 10/20 mg (n = 220), EZE/SIMVA 10/40 mg (n = 222) or ATV 20 g (n = 219) daily for 6 weeks. RESULTS: Greater (p < or = 0.001) reductions in low-density lipoprotein cholesterol (LDL-C) (the primary end-point) were achieved by switching to EZE/SIMVA 10/20 mg (26.2%) or 10/40 mg (30.1%) than by doubling the dose of ATV to 20 mg (8.5%). EZE/SIMVA 10/20 mg and 10/40 mg produced greater (p < or = 0.001) reductions in total cholesterol, non-high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B relative to ATV 20 mg. A reduction (p < or = 0.050) in C-reactive protein was observed with EZE/SIMVA 10/40 mg vs. ATV 20 mg. Similar reductions in triglycerides were observed across the three groups, and none of the treatments produced a significant change in HDL-C. A greater (p < or = 0.001) proportion of patients achieved LDL-C <2.5 mmol/l with EZE/SIMVA 10/20 mg (90.5%) and 10/40 mg (87.0%) than with ATV 20 mg (70.4%). Both EZE/SIMVA doses were generally well tolerated, with an overall safety profile similar to ATV 20 mg. CONCLUSIONS: EZE/SIMVA 10/20 and 10/40 mg provided greater lipid-altering efficacy than doubling the dose of ATV from 10 to 20 mg and were well tolerated in patients with T2D.