title: The effect of lowering LDL cholesterol on vascular access patency: post hoc analysis of the Study of Heart and Renal Protection.
abstract: OBJECTIVE
  Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with CKD, including dialysis patients, but the effect of lowering LDL-C on vascular access patency is unclear.
  
  
  METHODS
  The Study of Heart and Renal Protection (SHARP) randomized patients with CKD to 20 mg simvastatin plus 10 mg ezetimibe daily versus matching placebo. This study aimed to explore the effects of treatment on vascular access occlusive events, defined as any access revision procedure, access thrombosis, removal of an old dialysis access, or formation of new permanent dialysis access.
  
  
  RESULTS
  Among 2353 SHARP participants who had functioning vascular access at randomization, allocation to simvastatin plus ezetimibe resulted in a 13% proportional reduction in vascular access occlusive events (355 [29.7%] for simvastatin/ezetimibe versus 388 [33.5%] for placebo; risk ratio [RR], 0.87; 95% confidence interval [95% CI], 0.75 to 1.00; P=0.05). There was no evidence that the effects of treatment differed for any of the separate components of this outcome. To test the hypothesis raised by SHARP, comparable analyses were performed using the AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) trial cohort. AURORA did not provide independent confirmation (vascular access occlusive events: 352 [28.9%] for rosuvastatin versus 337 [27.6%] for placebo; RR, 1.06, 95% CI, 0.91 to 1.23; P=0.44). After combining the two trials, the overall effect of reducing LDL-C with a statin-based regimen on vascular access occlusive events was not statistically significant (707 [29.3%] with any LDL-C-lowering therapy versus 725 [30.5%] with placebo; RR, 0.95, 95% CI, 0.85 to 1.05; P=0.29).
  
  
  CONCLUSIONS
  Exploratory analyses from SHARP suggest that lowering LDL-C with statin-based therapy may improve vascular access patency, but there was no evidence of benefit in AURORA. Taken together, the available evidence suggests that any benefits of lowering LDL-C on vascular access patency are likely to be modest.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: William
authors.initials: W
authors.lastname: Herrington
authors.forename: Jonathan
authors.initials: J
authors.lastname: Emberson
authors.forename: Natalie
authors.initials: N
authors.lastname: Staplin
authors.forename: Lisa
authors.initials: L
authors.lastname: Blackwell
authors.forename: Bengt
authors.initials: B
authors.lastname: Fellström
authors.forename: Robert
authors.initials: R
authors.lastname: Walker
authors.forename: Adeera
authors.initials: A
authors.lastname: Levin
authors.forename: Lai Seong
authors.initials: LS
authors.lastname: Hooi
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tesar
authors.forename: Christina
authors.initials: C
authors.lastname: Reith
authors.forename: Richard
authors.initials: R
authors.lastname: Haynes
authors.forename: Colin
authors.initials: C
authors.lastname: Baigent
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Landray
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D002404:Catheterization; D008078:Cholesterol, LDL / Q000097:blood*; D020878:Device Removal; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000628:therapy*; D012086:Reoperation; D019821:Simvastatin / Q000627:therapeutic use*; D013927:Thrombosis / Q000517:prevention & control; D062666:Vascular Access Devices; D014654:Vascular Patency / Q000187:drug effects*
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019821:Simvastatin; D000069438:Ezetimibe
keywords: lipids; statins; vascular access