Short-term ezetimibe is well tolerated and effective in combination with statin therapy to treat elevated LDL cholesterol in HIV-infected patients.
BACKGROUND
Ezetimibe inhibits intestinal absorption of cholesterol.


METHODS
Multicentered double-blind, randomized, placebo-controlled, crossover study to determine the short-term safety, efficacy, and tolerability of ezetimibe in combination with ongoing statin therapy in HIV-infected adults with elevated low-density lipoprotein cholesterol (LDL-C). Participants on stable HAART with fasting LDL-C at least 130 mg/dl and stable statin were randomized to ezetimibe 10 mg daily or placebo for 12 weeks followed by 4 weeks of washout and then 12 weeks with alternative study assignment. Percentage and absolute change in LDL-C (primary endpoint), total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), apolipoprotein B, and high sensitivity C-reactive protein were compared. Changes in clinical symptoms and safety laboratory measurements were assessed.


RESULTS
Forty-four participants enrolled: 70% men, median age 49 years, 43% White/Non-Hispanic, median CD4 cell count 547 cells/microl, and 95% HIV RNA less than 50 copies/ml. Median (interquartile range) percentage change in LDL-C was -20.8% (-25.4, -10.7) with ezetimibe and -0.7% (-10.3,18.6) with placebo; the median within-participant effect of ezetimibe was -14.1% (-33.0, -5.0; P < 0.0001). Median difference in absolute LDL-C values between ezetimibe and placebo was -32 mg/dl (-58, -6, P < 0.0001). Significant differences in within-participant effect of ezetimibe were noted for total cholesterol -18.60% (-27.22, -11.67, P < 0.001), non-HDL-C -23.18% (-33.14, -14.36, P < 0.0001), and apolipoprotein B -8.73% (-18.75, 1.99, P = 0.02). No significant changes seen in HDL-C, triglyceride, or high sensitivity C-reactive protein. Ezetimibe was well tolerated. Adverse events were similar between phases.


CONCLUSIONS
The present short-term study found adding ezetimibe to ongoing statin therapy was well tolerated and effective in reducing LDL-C, total cholesterol, non-HDL-C, and apolipoprotein B. Adding ezetimibe to statin therapy offers reasonable treatment option for HIV-infected patients with elevated LDL-C.
Chow
Dominic
D
University of Hawaii, John A. Burns School of Medicine, Hawaii AIDS Clinical Research Program, 3675 Kilauea Avenue, 5th Floor, Young Building, Honolulu, HI 96816, USA. dominicc@hawaii.edu
Chen
Huichao
H
Glesby
Marshall J
MJ
Busti
Anthony
A
Souza
Scott
S
Andersen
Janet
J
Kohrs
Sharon
S
Wu
Julia
J
Koletar
Susan L
SL
D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D008078:Cholesterol, LDL / Q000097:blood*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D000069438:Ezetimibe; D005260:Female; D015658:HIV Infections / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe