Long-term safety and efficacy of triple combination ezetimibe/simvastatin plus extended-release niacin in patients with hyperlipidemia.

Abstract

The safety and efficacy of combination ezetimibe/simvastatin (E/S) plus extended-release niacin was assessed in 942 patients with type IIa/IIb hyperlipidemia for 64 weeks in a randomized, double-blind study. Patients received E/S (10/20 mg) plus niacin (to 2 g) or E/S (10/20 mg) for 64 weeks, or niacin (to 2 g) for 24 weeks and then E/S (10/20 mg) plus niacin (2 g) or E/S (10/20 mg) for an additional 40 weeks. The primary end point, the safety of E/S plus niacin, included prespecified adverse events (ie, liver, muscle, discontinuations due to flushing, gallbladder-related, cholecystectomy, fasting glucose changes, new-onset diabetes). The secondary end points included the percentage of change from baseline in high-density lipoprotein (HDL) cholesterol, triglycerides, non-HDL cholesterol, and low-density lipoprotein cholesterol, other lipids, lipoprotein ratios and high-sensitivity C-reactive protein. The anticipated niacin-associated flushing led to a greater rate of study discontinuations with the E/S plus niacin regimen than with E/S alone (0.7%, p <0.001). The rate of liver and muscle adverse events was low (<1%) in both groups. Four patients had gallbladder-related adverse events; 1 patient in the E/S and 1 in the E/S plus niacin group underwent cholecystectomy. The occurrence of new-onset diabetes was 3.1% for the E/S and 4.9% for the E/S plus niacin group. The fasting glucose levels increased to greater than baseline during the first 12 weeks (E/S, 3.2 mg/dl; E/S plus niacin, 7.7 mg/dl) and gradually decreased to pretreatment levels by 64 weeks in both groups. E/S plus niacin significantly improved HDL cholesterol, triglycerides, non-HDL cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and A-I, and lipoprotein ratios compared with E/S (p <or=0.004). The changes in high-sensitivity C-reactive protein were comparable for both groups. In conclusion, the combination of E/S plus niacin was generally well tolerated, aside from niacin-associated flushing, and was significantly superior to E/S alone in improving several lipoprotein parameters during a 64-week trial in patients with hyperlipidemia. E/S plus niacin provided a broad, lipid-altering therapeutic option for these patients, even in the presence of diabetes with glucose monitoring.

• Authors: Sergio Fazio, John R Guyton, Adam B Polis, Adeniyi J Adewale, Joanne E Tomassini, Nicholas W Ryan, Andrew M Tershakovec
• Journal: The American journal of cardiology (Am J Cardiol) Vol. 105 Issue 4 Pg. 487-94 (Feb 15 2010) ISSN: 1879-1913 [Electronic] United States
• PMID: 20152243 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Azetidines
• Biomarkers
• Cholesterol, HDL
• Cholesterol, LDL
• Delayed-Action Preparations
• Hypolipidemic Agents
• Lipoproteins
• Vitamin B Complex
• Niacin
• C-Reactive Protein
• Simvastatin
• Ezetimibe

Topics

• Adolescent
• Adult
• Aged
• Azetidines (administration & dosage, adverse effects, therapeutic use)
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Cholesterol, HDL (blood)
• Cholesterol, LDL (blood)
• Delayed-Action Preparations
• Double-Blind Method
• Drug Therapy, Combination
• Ezetimibe
• Female
• Follow-Up Studies
• Humans
• Hyperlipidemias (blood, diagnosis, drug therapy)
• Hypolipidemic Agents (administration & dosage, adverse effects, therapeutic use)
• Lipoproteins (blood)
• Male
• Middle Aged
• Niacin (administration & dosage, adverse effects, therapeutic use)
• Severity of Illness Index
• Simvastatin (administration & dosage, adverse effects, therapeutic use)
• Tennessee
• Time Factors
• Treatment Outcome
• Vitamin B Complex (administration & dosage, adverse effects, therapeutic use)