title: Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials.
abstract: Statin therapy is effective for the prevention of coronary heart disease and stroke in patients with mild-to-moderate chronic kidney disease, but its effects in individuals with more advanced disease, particularly those undergoing dialysis, are uncertain.
  
  
  
  We did a meta-analysis of individual participant data from 28 trials (n=183 419), examining effects of statin-based therapy on major vascular events (major coronary event [non-fatal myocardial infarction or coronary death], stroke, or coronary revascularisation) and cause-specific mortality. Participants were subdivided into categories of estimated glomerular filtration rate (eGFR) at baseline. Treatment effects were estimated with rate ratio (RR) per mmol/L reduction in LDL cholesterol.
  
  
  
  Overall, statin-based therapy reduced the risk of a first major vascular event by 21% (RR 0·79, 95% CI 0·77-0·81; p<0·0001) per mmol/L reduction in LDL cholesterol. Smaller relative effects on major vascular events were observed as eGFR declined (p=0·008 for trend; RR 0·78, 99% CI 0·75-0·82 for eGFR ≥60 mL/min per 1·73 m(2); 0·76, 0·70-0·81 for eGFR 45 to <60 mL/min per 1·73 m(2); 0·85, 0·75-0·96 for eGFR 30 to <45 mL/min per 1·73 m(2); 0·85, 0·71-1·02 for eGFR <30 mL/min per 1·73 m(2) and not on dialysis; and 0·94, 0·79-1·11 for patients on dialysis). Analogous trends by baseline renal function were seen for major coronary events (p=0·01 for trend) and vascular mortality (p=0·03 for trend), but there was no significant trend for coronary revascularisation (p=0·90). Reducing LDL cholesterol with statin-based therapy had no effect on non-vascular mortality, irrespective of eGFR.
  
  
  
  Even after allowing for the smaller reductions in LDL cholesterol achieved by patients with more advanced chronic kidney disease, and for differences in outcome definitions between dialysis trials, the relative reductions in major vascular events observed with statin-based treatment became smaller as eGFR declined, with little evidence of benefit in patients on dialysis. In patients with chronic kidney disease, statin-based regimens should be chosen to maximise the absolute reduction in LDL cholesterol to achieve the largest treatment benefits.
  
  
  
  UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Community Biomed Programme, Australian National Health and Medical Research Council, Australian National Heart Foundation.
authors.forename: William
authors.initials: WG
authors.lastname: Herrington
authors.forename: Jonathan
authors.initials: J
authors.lastname: Emberson
authors.forename: Borislava
authors.initials: B
authors.lastname: Mihaylova
authors.forename: Lisa
authors.initials: L
authors.lastname: Blackwell
authors.forename: Christina
authors.initials: C
authors.lastname: Reith
authors.forename: Marit
authors.initials: MD
authors.lastname: Solbu
authors.forename: Patrick
authors.initials: PB
authors.lastname: Mark
authors.forename: Bengt
authors.initials: B
authors.lastname: Fellström
authors.forename: Alan
authors.initials: AG
authors.lastname: Jardine
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Hallvard
authors.initials: H
authors.lastname: Holdaas
authors.forename: Jordan
authors.initials: J
authors.lastname: Fulcher
authors.forename: Richard
authors.initials: R
authors.lastname: Haynes
authors.forename: Martin
authors.initials: MJ
authors.lastname: Landray
authors.forename: Anthony
authors.initials: A
authors.lastname: Keech
authors.forename: John
authors.initials: J
authors.lastname: Simes
authors.forename: Rory
authors.initials: R
authors.lastname: Collins
authors.forename: Colin
authors.initials: C
authors.lastname: Baigent
mesh_terms: D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors