TY - JOUR
T1 - Long-Term Safety and Efficacy of Triple Combination Ezetimibe/Simvastatin Plus Extended-Release Niacin in Patients With Hyperlipidemia
AU - Fazio, Sergio
AU - Guyton, John R.
AU - Polis, Adam B.
AU - Adewale, Adeniyi J.
AU - Tomassini, Joanne E.
AU - Ryan, Nicholas W.
AU - Tershakovec, Andrew M.
N1 - Funding Information:
This study was funded by Merck/Schering-Plough Pharmaceuticals, Inc., North Wales, Pennsylvania. Drs. Fazio and Guyton have received honoraria from Merck/Schering-Plough Pharmaceuticals, Inc. (North Wales, Pennsylvania). Dr. Fazio has also received honoraria from Abbott Laboratories (North Chicago, Illinois), GlaxoSmithKline (Philadelphia, Pennsylvania), and research support from ISIS (Carlsbad, California)/Genzyme (Cambridge, Massachusetts) and Takeda (Osaka, Japan). Dr. Guyton has also received educational and research grants from Merck and Co., Inc. (Whitehouse Station, New Jersey) and consulting fees and honoraria from Abbott Laboratories (North Chicago, Illinois). Drs. Tershakovec, Tomassini, and Adewale and Mr. Polis and Mr. Ryan are employees of Merck and Co., Inc. (Whitehouse Station, New Jersey) and own stock and stock options in the company. Preventive cardiology
PY - 2010/2/15
Y1 - 2010/2/15
N2 - 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 ≤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.
AB - 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 ≤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.
UR - http://www.scopus.com/inward/record.url?scp=75349106253&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75349106253&partnerID=8YFLogxK
U2 - 10.1016/j.amjcard.2009.10.001
DO - 10.1016/j.amjcard.2009.10.001
M3 - Article
C2 - 20152243
AN - SCOPUS:75349106253
SN - 0002-9149
VL - 105
SP - 487
EP - 494
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 4
ER -