The effect of lowering LDL cholesterol on vascular access patency: Post hoc analysis of the study of heart and renal protection

William Herrington, Jonathan Emberson, Natalie Staplin, L Blackwell, Bengt Fellstrom, Robert Walker, Adeera Levin, Lai Hooi, Ziad Massy, Vladimir Tesar, Christina Reith, Richard Haynes, Colin Baigent, Martin Landray, David Wheeler, Charles Tomson, Christoph Wanner, Vera Krane, Alan Cass, Jonathan CraigBruce Neal, Lixin Jiang, Lawrence Agodoa, Mike Gaziano, Bertram Kasiske, Bo Feldt-Rasmussen, Udom Krairittichai, Vuddidhej Ophascharoensuk, Hallvard Holdaas, Andrzej Wiecek, Diederick Grobbee, Dick de Zeeuw, Carola Gronhagen-Riska, Tanaji Dasgupta, David Lewis, Marion Mafham, William Majoni, Karl Wallendszus, Richard Grimm, Terje Pedersen, Jonathan Tobert, Jane Armitage, Alex Baxter, Christopher Bray, Yiping Chen, Zhengming Chen, Michael Hill, Carol Knott, Sarah Parish, David Simpson, Peter Sleight, Alan Young, Rory Collins

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Abstract

Background and objectives 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. Design, setting, participants, & measurements The Study of Heart and Renal Protection (SHARP) randomized patients withCKDto20 mg simvastatinplus 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.

Original languageEnglish
Pages (from-to)914-919
Number of pages6
JournalClinical Journal of the American Society of Nephrology
Volume9
Issue number5
DOIs
Publication statusPublished - 2014

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