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.
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.


CONCLUSIONS
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.
Strony
John
J
Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0530, USA. john.strony@sprcorp.com
Hoffman
Robert
R
Hanson
Mary
M
Veltri
Enrico
E
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use; D018771:Arthralgia / Q000139:chemically induced; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D005500:Follow-Up Studies; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008148:Lovastatin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts / Q000706:statistics & numerical data; D017035:Pravastatin / Q000009:adverse effects / Q000627:therapeutic use*; D012141:Respiratory Tract Infections / Q000139:chemically induced; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D012852:Sinusitis / Q000139:chemically induced; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D008148:Lovastatin; D019821:Simvastatin; D000069438:Ezetimibe; D017035:Pravastatin