Long-term (48-week) safety of ezetimibe 10 mg/day coadministered with simvastatin compared to simvastatin alone in patients with primary hypercholesterolemia.
OBJECTIVE
This study evaluated the long-term safety and tolerability of ezetimibe/simvastatin coadministration therapy compared to simvastatin monotherapy in patients with primary hypercholesterolemia.


METHODS
After completing a 12-week randomized, double-blind, placebo-controlled, factorial, 10-armed study comparing ezetimibe 10 mg/simvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg; or placebo, 768 patients entered a 48-week extension, with randomized, blinded, reassignment of the simvastatin 10 mg, ezetimibe, and placebo groups to one of the ezetimibe/simvastatin groups. Patients previously receiving ezetimibe/simvastatin combination therapy, or simvastatin 20, 40, and 80 mg monotherapy continued the same therapies in this 7-arm extension study. During the extension study, investigators assessed adverse events (AEs).


RESULTS
Ezetimibe/simvastatin (n = 539) and simvastatin monotherapy (n = 229) groups generally had a similar incidence of all clinical AEs (73 vs. 69%), treatment-related AEs (14 vs. 11%), clinical serious AEs (SAE) (5.2 vs. 2.6%), treatment-related SAEs (0.2 vs. 0%), discontinuations due to all clinical AEs (4.5 vs. 2.6%) and discontinuations due to treatment-related AEs (2.8 vs. 2.2%), respectively. The incidence of total laboratory-related AEs for the ezetimibe/simvastatin and simvastatin monotherapy groups was also similar (12.2 vs. 11.9%), as was treatment-related laboratory AEs (6.2 vs. 5.3%), laboratory SAEs (0 vs. 0%), treatment-related laboratory SAEs (0 vs. 0%), discontinuations due to laboratory AEs (3.0 vs. 0.9%) and discontinuations due to treatment-related laboratory AEs (3.0 vs. 0.4%), respectively. There were no cases of myopathy, rhabdomyolysis, or serious hepatotoxicity observed in any group during this extension study.


CONCLUSIONS
During this 48-week extension study, the coadministration of ezetimibe/simvastatin was generally as well tolerated as simvastatin monotherapy. The direct application of study observations to clinical practice is limited by patient selection criteria and dosage regime, which randomly applied relatively high doses rather than titration which often occurs in clinical practice.
Bays
Harold
H
Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA. hbaysmd@aol.com
Sapre
Aditi
A
Taggart
William
W
Liu
Ji
J
Capece
Rachel
R
Tershakovec
Andrew
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects*; D000069438:Ezetimibe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects*; D013997:Time Factors
D000924:Anticholesteremic Agents; D001384:Azetidines; D019821:Simvastatin; D000069438:Ezetimibe