title: Lipid lowering efficacy and safety of Ezetimibe combined with rosuvastatin compared with titrating rosuvastatin monotherapy in HIV-positive patients.
abstract: BACKGROUND
  HIV-infected patients on antiretroviral therapy frequently develop dyslipidemias and, despite therapy with potent lipid-lowering agents, a high percentage does not achieve guideline recommended lipid targets. In this study, we examined the efficacy of combination treatment with a statin and the cholesterol transport blocker, ezetimibe, vs. monotherapy with a statin in HIV-infected patients not achieving lipid goals.
  
  
  METHODS
  This was a 12-week, prospective, randomized, open-label clinical trial. Patients were eligible if they had an apolipoprotein B (apoB) >0.80 g/L despite therapy with rosuvastatin 10 mg daily for a minimum of 12 weeks. Patients were randomized to take ezetimibe 10 mg/rosuvastatin 10 mg or rosuvastatin 20 mg for 12 weeks. Percentage and absolute change in apoB (primary outcome), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apoliporpotein A1 (apoA1), apoB/apoA1, TC/HDL-C, atherogenic index of plasma (API), and high-sensitivity C-reactive protein (hsCRP) were compared. Changes in safety parameters (such as AST, ALT, CK) and clinical symptoms were also assessed.
  
  
  RESULTS
  Forty-three patients (23 on ezetimibe 10 mg/rosuvastatin 10 mg and 20 on rosuvastatin 20 mg) completed the trial. Baseline characteristics did not differ between the groups. Significant improvements in apoB were seen with both ezetimibe plus rosuvastatin (mean of -0.17 g/L, p < 0.001) and rosuvastatin 20 mg (mean of -0.13 g/L, p = 0.03) treatment groups, but did not differ between groups (p = 0.53). Significant between-group differences were observed for mean TC (-1.01 mmol/L vs. -0.50 mmol/L, p = 0.03), TG (-0.62 mmol/L vs -0.17 mmol/L, p = 0.03), and non-HDL-C (-0.97 mmol/L vs. -0.53 mmol/L, p = 0.03) all in favour of the ezetimibe plus rosuvastatin group. Two patients, both in the rosuvastatin 20 mg group, experienced mild myalgias; neither discontinued the study.
  
  
  CONCLUSIONS
  The addition of ezetimibe to rosuvastatin appears to be safe in patients with HIV. Furthermore, the combination of ezetimibe and rosuvastatin improved TG, AIP and non-HDL cholesterol levels more than a dose increase in rosuvastatin in patients with HIV-associated dyslipidemia.
authors.affiliation: Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, Canada. rsaeedi@providencehealth.bc.ca.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Saeedi
authors.affiliation: Experimental Medicine Program, Faculty of Medicine, University of British Columbia, Vancouver, Canada. kevinwjohns@me.com.
authors.forename: Kevin
authors.initials: K
authors.lastname: Johns
authors.affiliation: Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, Canada. jifr@mail.ubc.ca.
authors.forename: Jiri
authors.initials: J
authors.lastname: Frohlich
authors.affiliation: Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, Canada. Matthew.bennett@vch.ca.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Bennett
authors.affiliation: Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, Canada. gbondy@providencehealth.bc.ca.|Departments of Medicine and Pathology, Faculty of Medicine, University of British Columbia, Vancouver, Canada. gbondy@providencehealth.bc.ca.
authors.forename: Gregory
authors.initials: G
authors.lastname: Bondy
mesh_terms: D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003710:Demography; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068718:Rosuvastatin Calcium / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D000068718:Rosuvastatin Calcium; D000069438:Ezetimibe