title: Cost-effectiveness of Simvastatin plus Ezetimibe for Cardiovascular Prevention in CKD: Results of the Study of Heart and Renal Protection (SHARP).
abstract: BACKGROUND
  Simvastatin, 20mg, plus ezetimibe, 10mg, daily (simvastatin plus ezetimibe) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease (CKD) in the Study of Heart and Renal Protection (SHARP), but its cost-effectiveness is unknown.
  
  
  METHODS
  Cost-effectiveness of simvastatin plus ezetimibe in SHARP, a randomized controlled trial.
  
  
  METHODS
  9,270 patients with CKD randomly assigned to simvastatin plus ezetimibe versus placebo; participants in categories by 5-year cardiovascular risk (low, <10%; medium, 10%-<20%; or high, ≥20%) and CKD stage (3, 4, 5 not on dialysis, or on dialysis therapy).
  Assessment during SHARP follow-up from the UK perspective; long-term projections.
  
  
  METHODS
  Simvastatin plus ezetimibe (2015 UK £1.19 per day) during 4.9 years' median follow-up in SHARP; scenario analyses with high-intensity statin regimens (2015 UK £0.05-£1.06 per day).
  
  
  RESULTS
  Additional health care costs per major atherosclerotic event avoided and per quality-adjusted life-year (QALY) gained.
  
  
  RESULTS
  In SHARP, the proportional reductions per 1mmol/L of low-density lipoprotein (LDL) cholesterol reduction with simvastatin plus ezetimibe in all major atherosclerotic events of 20% (95% CI, 6%-32%) and in the costs of vascular hospital episodes of 17% (95% CI, 4%-28%) were similar across participant categories by cardiovascular risk and CKD stage. The 5-year reduction in major atherosclerotic events per 1,000 participants ranged from 10 in low-risk to 58 in high-risk patients and from 28 in CKD stage 3 to 36 in patients on dialysis therapy. The net cost per major atherosclerotic event avoided with simvastatin plus ezetimibe compared to no LDL-lowering regimen ranged from £157,060 in patients at low risk to £15,230 in those at high risk (£30,500-£39,600 per QALY); and from £47,280 in CKD stage 3 to £28,180 in patients on dialysis therapy (£13,000-£43,300 per QALY). In scenario analyses, generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost.
  
  
  CONCLUSIONS
  High-intensity statin-alone regimens were not studied in SHARP.
  
  
  CONCLUSIONS
  Simvastatin plus ezetimibe prevented atherosclerotic events in SHARP, but other less costly statin regimens are likely to be more cost-effective for reducing cardiovascular risk in CKD.
authors.affiliation: Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. Electronic address: boby.mihaylova@dph.ox.ac.uk.
authors.forename: Borislava
authors.initials: B
authors.lastname: Mihaylova
authors.affiliation: Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Iryna
authors.initials: I
authors.lastname: Schlackow
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: Herrington
authors.affiliation: Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Jingky
authors.initials: J
authors.lastname: Lozano-Kühne
authors.affiliation: Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Seamus
authors.initials: S
authors.lastname: Kent
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Emberson
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Christina
authors.initials: C
authors.lastname: Reith
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Haynes
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, Sydney, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Cass
authors.affiliation: School of Public Health, University of Sydney, Sydney, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Craig
authors.affiliation: Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Alastair
authors.initials: A
authors.lastname: Gray
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Rory
authors.initials: R
authors.lastname: Collins
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Landray
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Colin
authors.initials: C
authors.lastname: Baigent
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000191:economics* / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D003362:Cost-Benefit Analysis; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000191:economics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications; D019821:Simvastatin / Q000191:economics* / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D019821:Simvastatin; D000069438:Ezetimibe
keywords: Chronic kidney disease (CKD); LDL-cholesterol lowering; atherosclerotic events; cardiovascular disease risk; cost-effectiveness; ezetimibe; health care costs; lipid lowering; quality-adjusted life-year (QALY); statin