Extended-Release Niacin for Dyslipidemic Patients with HIV Infection
Speaker: James H. Stein, MD, Associate Professor, Section of Cardiovascular Medicine, Department of Medicine, University of Wisconsin Medical School, Madison, Wisconsin
Extended-release (ER) niacin (Niaspan, Kos), well known for its value in lowering low-density lipoprotein-cholesterol (LDL-C) and total cholesterol and its ability to increase HDL-cholesterol (HDL-C) in patients with hypercholes-terolemia and mixed dyslipidemia, has proved safe, well tolerated, and effective for treating dyslipidemia in patients with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy (ART).
A total of 37 patients were initially enrolled into a two-step, open-label, dose-escalating, 48-week, single-arm protocol. All of the patients had triglyceride levels above 200 mg/dl and non-HDL-C levels above 180 mg/dl.
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Step one included a four-week lipid-lowering diet, therapeutic lifestyle changes, and an activity guide. In step two, patients received ER niacin 500 mg nightly, titrated every four to six weeks to a target dose of 2,000 mg daily.
The primary endpoint of the study was to evaluate the safety and tolerability of ER niacin therapy over 44 weeks of lipid goal-directed therapy. Secondary endpoints included the product’s efficacy over 20 weeks and 44 weeks in lowering non-HDL-C, raising HDL-C, lowering triglycerides, and bringing about composite lipid goals over 44 weeks.
Of 33 men who entered step 2, 32 completed the study. Although there was some concern about insulin resistance and hepatotoxicity, which are common in HIV-infected individuals receiving niacin, ER niacin at doses up to 200 mg/day was safe and well tolerated. There were no significant changes in uric acid or aminotransferase levels. Although fasting glucose levels increased minimally at week 12 of treatment, the increase was transient, and there were no changes at weeks 24 or 48.
ART regimens were changed for five patients over the course of the study, but these adjustments did not appear to significantly affect the results of their dyslipidemia treatment.
Nearly 25% of patients (7 of 32) met the strict composite lipid goal at week 44, a rate better than that reported in similar statin and fibrate studies. Eight patients met the non-HDL-C criteria, 11 men met the LDL-C criteria, and 27 subjects met the triglyceride criteria.
On the basis of these findings, it was recommended that ER niacin, in combination with other lipid-lowering drugs, be studied in HIV-positive patients.
Long-Term Fenofibrate/Ezetimibe Effective in Mixed Hyperlipidemia
Speaker: James M. McKenney, PharmD, President and Chief Executive Officer, National Clinical Research, and Professor Emeritus, Virginia Commonwealth University School of Medicine, Richmond, Virginia
Long-term coadministration of fenofibrate (Antara, Reliant; TriCor, Abbott) and ezetimibe (Merck/Schering-Plough) provided superior lipid-altering effects when compared with fenofibrate monotherapy, and it was well tolerated for up to 48 weeks in patients with mixed hyperlipidemia.
Mixed hyperlipidemia is associated with a high risk of coronary heart disease (CHD). Patients require treatment that effectively lowers LDL-C, triglyceride, and non-HDL-C levels while raising HDL-C concentrations. Fenofibrate and ezetim-ibe offer complementary effects on the lipid profile and together may improve mixed hyperlipidemia.
Researchers decided to compare the long-term safety and efficacy of fenofibrate plus ezetimibe with fenofibrate monotherapy in patients with mixed hyperlipidemia. Initially, 625 patients were enrolled in a 12-week base study and were randomly selected, in a 3:3:3:1 ratio, to receive fenofibrate 160 mg/day plus ezetimibe 10 mg/day (185 patients), ezetimibe 10 mg a day (187 patients), a day (189 patients), or placebo (64 patients). Of the 587 patients who completed the 12-week base study, 576 continued into a 48-week extension study, with 340 patients receiving fenofibrate plus ezetimibe and 236 patients receiving fenofibrate monotherapy.
The primary efficacy variable was the percentage of change in LDL-C levels from the baseline of the initial study to the study’s endpoint in the extension, from 0 to 48 weeks. Secondary efficacy endpoints included the percentage of change from the baseline to the study’s endpoint in total cholesterol, HDL-C, triglycerides, non-HDL-C, apolipoprotein B (apo B), apo A-1, and high-sensitivity C-reactive protein (hs CRP).
Coadministration of fenofibrate plus was well tolerated during the 48-week extension study, and the safety profile was similar to that of fenofibrate monotherapy. The fenofibrate/ezetimibe regimen also resulted in significantly greater percentage reductions, compared with canadian fenofibrate monotherapy in LDL-C (-22°% vs. -9°%), total cholesterol (-23°% vs. -14%), TG (-46% vs. -42%) non-HDL-C (-32% vs. -19%) and apo B (-25% vs. -16%). Furthermore, HDL-C was significantly greater (10% vs. 8%), and the differences in hs CRP showed a trend in reduction (-25% vs. -21%). The changes in apo A-1, however, did not differ significantly between the groups (-10% vs. -8%).