PMID- 15811480
OWN - NLM
STAT- MEDLINE
DCOM- 20050720
LR  - 20151119
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 27
IP  - 2
DP  - 2005 Feb
TI  - Long-term safety and, tolerability profiles and lipid-modifying efficacy of 
      ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, 
      randomized, double-blind, placebo-controlled, 48-week extension study.
PG  - 174-84
AB  - BACKGROUND: Ezetimibe (EZE) is a cholesterol-lowering drug that inhibits 
      absorption of dietary and biliary cholesterol across the intestinal wall without 
      affecting absorption of bile acids, fatty acids, fat-soluble vitamins, or 
      triglycerides. It has a complementary mechanism of action to the statins, which 
      inhibit cholesterol synthesis in the liver. Coadministration of EZE and statins 
      provides inhibition of 2 sources of cholesterol, leading to greater reductions in 
      low-density lipoprotein cholesterol (LDL-C) than with either agent alone. 
      OBJECTIVES: This study evaluated the long-term safety and tolerability profiles 
      and lipid-modifying efficacy of treatment with EZE 10 mg/d plus simvastatin 
      (SIMVA) 10, 20, 40, or 80 mg/d for 48 weeks in patients with primary 
      hypercholesterolemia. METHODS: This was an extension of a multicenter, 
      double-blind, placebo (PBO)-controlled base study in which hypercholesterolemic 
      patients were randomized to receive EZE 10 mg/d or PBO in addition to their 
      current statin for 8 weeks. Patients who successfully completed the base study 
      could enter the extension study if they were willing to switch from their current 
      statin to an approximately equipotent dose of SIMVA for the 54-week study period. 
      After a 6-week open-label SIMVA run-in phase, patients were rerandomized to 
      receive EZE 10 mg/d or PBO in a 4:1 ratio, respectively, for 48 weeks. At each 
      clinic visit, beginning at week 12, the dose of SIMVA was titrated upward until 
      patients reached their National Cholesterol Education Program Adult Treatment 
      Panel II LDL-C goal or the maximum SIMVA dose of 80 mg/d. Safety/tolerability and 
      lipid efficacy parameters were assessed at 12-week intervals. RESULTS: Of 433 
      patients entering the extension study, 355 were randomized to receive EZE and 78 
      were randomized to receive PBO. Baseline demographic characteristics and lipid 
      levels were similar between treatment groups. Overall, coadministration of EZE + 
      SIMVA was well tolerated. There were no clinically meaningful differences between 
      the EZE and PBO groups with regard to the incidence of treatment-related adverse 
      events (AEs) (19% vs 17%, respectively), discontinuations due to AEs (7% vs 10%), 
      serious AEs (12% vs 17%), consecutive elevations in liver function tests > or =3 
      times the upper limit of normal (ULN) (0.3% vs 0%), or elevations in creatine 
      kinase > or =10 times the ULN (both, 0%). As in the base study, LDL-C levels were 
      significantly lower with the addition of EZE to SIMVA compared with the addition 
      of PBO (-24% vs 3%; P < 0.001). CONCLUSION: In these patients with primary 
      hypercholesterolemia, EZE 10 mg/d added to ongoing SIMVA treatment for 48 weeks 
      had a favorable safety and tolerability profile and was more efficacious than 
      SIMVA monotherapy.
FAU - Masana, Luis
AU  - Masana L
AD  - Universitat Rovira i Virgili, Reus-Tarragona, Madrid, Spain.
FAU - Mata, Pedro
AU  - Mata P
FAU - Gagne, Claude
AU  - Gagne C
FAU - Sirah, Waheeda
AU  - Sirah W
FAU - Cho, Meehyung
AU  - Cho M
FAU - Johnson-Levonas, Amy O
AU  - Johnson-Levonas AO
FAU - Meehan, Alan
AU  - Meehan A
FAU - Troxell, John K
AU  - Troxell JK
FAU - Gumbiner, Barry
AU  - Gumbiner B
CN  - Ezetimibe Study Group
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Azetidines)
RN  - 0 (Lipoproteins)
RN  - AGG2FN16EV (Simvastatin)
RN  - EOR26LQQ24 (Ezetimibe)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anticholesteremic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Azetidines/administration & dosage/adverse effects/*therapeutic use
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Ezetimibe
MH  - Female
MH  - Humans
MH  - Hypercholesterolemia/*drug therapy
MH  - Lipoproteins/blood
MH  - Male
MH  - Middle Aged
MH  - Simvastatin/administration & dosage/adverse effects/*therapeutic use
MH  - Time Factors
EDAT- 2005/04/07 09:00
MHDA- 2005/07/21 09:00
CRDT- 2005/04/07 09:00
PHST- 2004/11/30 00:00 [accepted]
PHST- 2005/04/07 09:00 [pubmed]
PHST- 2005/07/21 09:00 [medline]
PHST- 2005/04/07 09:00 [entrez]
AID - S0149-2918(05)00030-5 [pii]
AID - 10.1016/j.clinthera.2005.02.011 [doi]
PST - ppublish
SO  - Clin Ther. 2005 Feb;27(2):174-84. doi: 10.1016/j.clinthera.2005.02.011.