title: Comparative efficacy and adverse effects of the addition of ezetimibe to statin versus statin titration in chronic kidney disease patients.
abstract: OBJECTIVE
  The recent SHARP trial clearly demonstrated that a reduction in low-density lipoprotein (LDL) cholesterol with a daily regimen of simvastatin plus ezetimibe safely reduced the incidence of major atherosclerotic events in patients with chronic kidney disease (CKD). We aimed to compare the efficacy of and adverse effects from statin uptitration versus statin in combination with ezetimibe since only a few studies have addressed this question.
  
  
  METHODS
  This was a randomized, open-label, multicenter trial that included 286 patients with CKD whose LDL cholesterol levels were not reduced below 120 mg/dl despite a minimum dose of statin therapy. Patients received double doses of statin or usual statin dose with the addition of ezetimibe 10 mg daily. The observation period was 1 year during which time patients were checked regularly in clinic for adverse effects as well as for usual laboratory examinations. The key prespecified outcome was the incidence of adverse effects, which included skeletal muscle complaints, myalgia, muscle weakness, and muscle cramps with and without elevated CK levels. Increases in alanine transaminase (ALT) or aspartate transaminase (AST) levels >2 times the upper limit of normal (ULN) were considered clinically significant adverse effects.
  
  
  RESULTS
  Adverse events occurred in 9/145 in the combination group and in 24/141 in the statin uptitration group (p < 0.01). Moreover, in patients with CKD of stages 3-5, rates were 6/58 in the combination group versus 20/52 in the statin uptitration group (p < 0.01). No serious adverse effects such as rhabdomyolysis were noted in either group. Serum creatinine levels remained essentially unchanged in both groups except in CKD stages 4 and 5. Reductions in LDL cholesterol were similar between the two groups at the start of and at the end of the study. During the study, no atherosclerotic events were reported in either group.
  
  
  CONCLUSIONS
  When statin uptitration produces adverse effects such as myopathy, combination therapy with ezetimibe is recommended instead of statin alone.
authors.affiliation: Department of Nephrology, Saitama Medical University.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hiroo
authors.initials: H
authors.lastname: Kumagai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shuto
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D007564:Japan; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe
keywords: cardiovascular diseases; chronic kidney disease; myopathy; statin