RESEARCH - Tolerability and effects on lipids of ezetimibe coadministered with pravastatin or simvastatin for 12 months

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Clin Ther. 2008 Dec;30(12):2280-97.

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.

Strony J, Hoffman R, Hanson M, Veltri E.

Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0530, USA.

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.

PMID: 19167588

http://www.ncbi.nlm.nih.gov/pubmed/19167588

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