PMID- 18782465
OWN - NLM
STAT- MEDLINE
DCOM- 20090123
LR  - 20190911
IS  - 1473-4877 (Electronic)
IS  - 0300-7995 (Linking)
VI  - 24
IP  - 10
DP  - 2008 Oct
TI  - Long-term (48-week) safety of ezetimibe 10 mg/day coadministered with simvastatin 
      compared to simvastatin alone in patients with primary hypercholesterolemia.
PG  - 2953-66
LID - 10.1185/03007990802365094 [doi]
AB  - OBJECTIVE: This study evaluated the long-term safety and tolerability of 
      ezetimibe/simvastatin coadministration therapy compared to simvastatin 
      monotherapy in patients with primary hypercholesterolemia. RESEARCH DESIGN AND 
      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). MAIN OUTCOME MEASURES AND 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.
FAU - Bays, Harold
AU  - Bays H
AD  - Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, 
      USA. hbaysmd@aol.com
FAU - Sapre, Aditi
AU  - Sapre A
FAU - Taggart, William
AU  - Taggart W
FAU - Liu, Ji
AU  - Liu J
FAU - Capece, Rachel
AU  - Capece R
FAU - Tershakovec, Andrew
AU  - Tershakovec A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20080908
PL  - England
TA  - Curr Med Res Opin
JT  - Current medical research and opinion
JID - 0351014
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Azetidines)
RN  - AGG2FN16EV (Simvastatin)
RN  - EOR26LQQ24 (Ezetimibe)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anticholesteremic Agents/administration & dosage/*adverse effects
MH  - Azetidines/*administration & dosage/*adverse effects
MH  - Ezetimibe
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Hypercholesterolemia/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Simvastatin/*administration & dosage/*adverse effects
MH  - Time Factors
EDAT- 2008/09/11 09:00
MHDA- 2009/01/24 09:00
CRDT- 2008/09/11 09:00
PHST- 2008/09/11 09:00 [pubmed]
PHST- 2009/01/24 09:00 [medline]
PHST- 2008/09/11 09:00 [entrez]
AID - 4628e [pii]
AID - 10.1185/03007990802365094 [doi]
PST - ppublish
SO  - Curr Med Res Opin. 2008 Oct;24(10):2953-66. doi: 10.1185/03007990802365094. Epub 
      2008 Sep 8.