PMID- 19167588
OWN - NLM
STAT- MEDLINE
DCOM- 20090319
LR  - 20151119
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 30
IP  - 12
DP  - 2008 Dec
TI  - Tolerability and effects on lipids of ezetimibe coadministered with pravastatin 
      or simvastatin for twelve months: results from two open-label extension studies 
      in hypercholesterolemic patients.
PG  - 2280-97
LID - 10.1016/j.clinthera.2008.12.008 [doi]
AB  - OBJECTIVE: The aim of these studies was to assess the long-term tolerability and 
      effects on lipids of ezetimibe coadministered with pravastatin or simvastatin 
      during treatment of hypercholesterolemic patients. METHODS: Two separate 
      12-month, open-label extension studies enrolled patients who had successfully 
      completed one of three 12-week, double-blind, placebo-controlled trials of 
      ezetimibe coadministered with pravastatin, lovastatin, or simvastatin. In the 
      extensions, the initial dose of each drug administered was 10 mg/d, with the 
      option to up-titrate the statins if low-density lipoprotein cholesterol (LDL-C) 
      goals were not met. Tolerability was assessed using monitoring of clinical and 
      laboratory adverse events (AEs). Changes from baseline in LDL-C, total 
      cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were 
      calculated. RESULTS: Overall, 436 patients received ezetimibe + pravastatin 10 to 
      40 mg/d, including patients from the parent studies who received coadministration 
      treatment but did not continue in the extension studies; 359 patients received 
      ezetimibe + simvastatin 10 to 80 mg/d in the extension study. The majority of 
      patients in both studies were white (ezetimibe + pravastatin, 374 [86%]; 
      ezetimibe + simvastatin, 314 [87%]) and female (ezetimibe + pravastatin, 246 
      [56%]; ezetimibe + simvastatin, 210 [58%]). The mean ages were 55.7 and 57.7 
      years and the mean body mass indexes were 29.4 and 28.8 kg/m2 in the ezetimibe + 
      pravastatin and ezetimibe + simvastatin studies, respectively. The most commonly 
      reported AEs with ezetimibe + pravastatin were upper respiratory tract infection 
      (78 [18%]), headache (47 [11%]), musculoskeletal pain (45 [10%]), arthralgia (43 
      [10%]), and sinusitis (42 [10%]); with ezetimibe + simvastatin, they were upper 
      respiratory tract infection (67 [19%]), arthralgia (39 [11%]), and 
      musculoskeletal pain (37 [10%]). AEs considered treatment related were reported 
      in 98 (22%) and 80 (22%) patients in the ezetimibe + pravastatin and ezetimibe + 
      simvastatin studies, respectively. Serious AEs were reported in 29 patients (7%) 
      who received ezetimibe + pravastatin and 36 patients (10%) who received ezetimibe 
      + simvastatin; <1% were considered treatment related in either study. Forty-one 
      (9%) and 29 patients (8%), respectively, were withdrawn due to AEs. One death 
      occurred due to cardiopulmonary arrest in the ezetimibe + simvastatin study and 
      was not considered treatment related. Percentage changes from baseline in LDL-C 
      were -36.5% and -40.4% in patients who received ezetimibe + pravastatin and 
      ezetimibe + simvastatin. CONCLUSION: In these 12-month, open-label extension 
      studies in these patients with hypercholesterolemia, ezetimibe + pravastatin or 
      simvastatin was generally well tolerated. Both treatments were associated with 
      maintaining improvements in lipid parameters throughout the studies in these 
      patients.
FAU - Strony, John
AU  - Strony J
AD  - Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0530, USA. 
      john.strony@sprcorp.com
FAU - Hoffman, Robert
AU  - Hoffman R
FAU - Hanson, Mary
AU  - Hanson M
FAU - Veltri, Enrico
AU  - Veltri E
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
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 (Cholesterol, HDL)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Triglycerides)
RN  - 9LHU78OQFD (Lovastatin)
RN  - AGG2FN16EV (Simvastatin)
RN  - EOR26LQQ24 (Ezetimibe)
RN  - KXO2KT9N0G (Pravastatin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anticholesteremic Agents/adverse effects/therapeutic use
MH  - Arthralgia/chemically induced
MH  - Azetidines/adverse effects/*therapeutic use
MH  - Body Mass Index
MH  - Cholesterol, HDL/blood
MH  - Cholesterol, LDL/blood
MH  - Drug Therapy, Combination
MH  - Ezetimibe
MH  - Female
MH  - Follow-Up Studies
MH  - Headache/chemically induced
MH  - Humans
MH  - Hypercholesterolemia/blood/*drug therapy
MH  - Lovastatin/adverse effects/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Patient Dropouts/statistics & numerical data
MH  - Pravastatin/adverse effects/*therapeutic use
MH  - Respiratory Tract Infections/chemically induced
MH  - Simvastatin/adverse effects/*therapeutic use
MH  - Sinusitis/chemically induced
MH  - Treatment Outcome
MH  - Triglycerides/blood
EDAT- 2009/01/27 09:00
MHDA- 2009/03/20 09:00
CRDT- 2009/01/27 09:00
PHST- 2008/10/03 00:00 [accepted]
PHST- 2009/01/27 09:00 [entrez]
PHST- 2009/01/27 09:00 [pubmed]
PHST- 2009/03/20 09:00 [medline]
AID - S0149-2918(08)00434-7 [pii]
AID - 10.1016/j.clinthera.2008.12.008 [doi]
PST - ppublish
SO  - Clin Ther. 2008 Dec;30(12):2280-97. doi: 10.1016/j.clinthera.2008.12.008.