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.