Long-term safety and efficacy of triple combination ezetimibe/simvastatin plus extended-release niacin in patients with hyperlipidemia.
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.
Division of Cardiovascular Medicine, Vanderbilt University, Nashville, Tennessee, USA. sergio.fazio@vanderbilt.edu
Sergio
S
Fazio
John R
JR
Guyton
Adam B
AB
Polis
Adeniyi J
AJ
Adewale
Joanne E
JE
Tomassini
Nicholas W
NW
Ryan
Andrew M
AM
Tershakovec
D000293:Adolescent; D000328:Adult; D000368:Aged; D001384:Azetidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013714:Tennessee; D013997:Time Factors; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D001384:Azetidines; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014803:Vitamin B Complex; D009525:Niacin; D002097:C-Reactive Protein; D019821:Simvastatin; D000069438:Ezetimibe