The Effect of Lowering LDL Cholesterol on Vascular Access Patency

Herrington, William G; Emberson, Jonathan; Staplin, Natalie; Blackwell, Lisa; Fellström, Bengt; Walker, Robert; Levin, Adeera; Hooi, Lai Seong; Massy, Ziad A.; Tesař, Vladimı́r; Reith, Christina; Haynes, Richard; Baigent, Colin; Landray, Martin J

doi:10.2215/cjn.10371013

Cited by 19 publications

(13 citation statements)

References 28 publications

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“…A reduction in dialysis access revisions or complications was also observed, but in previous exploratory analyses, this finding was not confirmed in data from the AURORA trial, suggesting that any benefits of lowering LDL-C on vascular access patency are likely to be modest [30]. …”

Section: Discussionmentioning

confidence: 99%

Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection

et al. 2017

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BackgroundReducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with chronic kidney disease (CKD), with no evidence of an excess risk of cancer or death from any non-vascular cause. However, non-randomized data have suggested that statin therapy may have effects (both adverse and beneficial) on particular non-vascular conditions that do not cause death.MethodsThe Study of Heart and Renal Protection (SHARP) randomized patients with CKD to simvastatin 20 mg plus ezetimibe 10 mg (simvastatin/ezetimibe) daily versus matching placebo. Participants were followed up at least 6 monthly and all post-randomization serious adverse events (SAEs) were recorded. This supplementary analysis reports the effects of treatment on non-vascular SAEs, overall, by system of disease, by baseline characteristics, and by duration of follow-up.ResultsDuring a median of 4.9 years follow-up, similar numbers of participants in the two groups experienced at least one non-vascular SAE (3551 [76.4%] simvastatin/ezetimibe vs 3537 [76.6%] placebo; risk ratio [RR] 0.99, 95% confidence interval [CI] 0.95–1.04). There was no good evidence of any significant effect of simvastatin/ezetimibe on SAEs attributed to any particular nonvascular disease system (of 43 comparisons, only 3 yielded an uncorrected p value < 0.05, of which the smallest was p = 0.02). The relative risk of any nonvascular SAE did not vary significantly among particular prognostic subgroups or by duration of follow-up.ConclusionsIn the SHARP trial, allocation to simvastatin/ezetimibe combination therapy was not associated with any significant non-vascular hazard.Trials registrationSHARP was retrospectively registered after the first participant was enrolled in 2003 at ISRCTN (ISRCTN54137607 on 31 January 2005: http://www.isrctn.com/ISRCTN54137607) and ClinicalTrials.gov (NCT00125593 on 29 July 2005: https://clinicaltrials.gov/ct2/show/NCT00125593).Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0545-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection

et al. 2017

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“…Exploratory analyses of 2352 participants with a pre‐existing vascular access from the Study of Heart and Renal Protection (SHARP) trial showed a 13% reduction in vascular access occlusive events in participants treated with simvastatin (20 mg) plus ezetimibe (10 mg) compared to placebo (RR 0.87, 95% CI 0.75‐1.00; P = .05). This finding was not replicated in a post hoc analysis of a RCT of 2439 dialysis patients where 29% receiving rosuvastatin had an occlusive vascular access event vs 28% in the placebo group (RR 1.06, 95% CI 0.91‐1.23) . A case–control study of 60 incident dialysis patients suggested a treatment benefit of folic acid and/or statin on primary patency loss of AVFs compared to nonuse .…”

Section: Clinical Trials Of Statin Therapy and Vascular Access Outcommentioning

confidence: 97%

The pathogenesis of hemodialysis vascular access failure and systemic therapies for its prevention: Optimism unfulfilled

Viecelli

Mori

Roy‐Chaudhury³

et al. 2017

Seminars in Dialysis

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In patients receiving hemodialysis, the provision of safe and effective vascular access using an arteriovenous fistula or graft is regarded as a critical priority by patients and health professionals. Vascular access failure is associated with morbidity and mortality, such that strategies to prevent these outcomes are essential. Inadequate vascular remodeling and neointimal hyperplasia resulting in stenosis and frequently thrombosis are critical to the pathogenesis of access failure. Systemic medical therapies with pleiotropic effects including antiplatelet agents, omega-3 polyunsaturated fatty acids (fish oils), statins, and inhibitors of the renin-angiotensin-aldosterone system (RAAS) may reduce vascular access failure by promoting vascular access maturation and reducing stenosis and thrombosis through antiproliferative, antiaggregatory, anti-inflammatory and vasodilatory effects. Despite such promise, the results of retrospective analyses and randomized controlled trials of these agents on arteriovenous fistula and graft outcomes have been mixed. This review describes the current understanding of the pathogenesis of arteriovenous fistula and graft failure, the biological effects of antiplatelet agents, fish oil supplementation, RAAS blockers and statins that may be beneficial in improving vascular access survival, results from clinical trials that have investigated the effect of these agents on arteriovenous fistula and graft outcomes, and it explores future therapeutic approaches combining these agents with novel treatment strategies.

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“…Our search identified one RCT and six RCS with chronic renal failure undergoing HD therapy using AVFs (7,(12)(13)(14)(15)(16)(17). We present reasons for study exclusion and progress through stages in Figure 1.…”

Section: Study Characteristics and Quality Assessmentmentioning

confidence: 99%

“…The AURORA trial was an international, multicenter, large-scale statin trial among hemodialysis patients (25). To test the effect of statins on AVFs vascular access patency, Herrington et al performed a retrospective cohort study using the AURORA database (14), finding that there was no significant effect on vascular access occlusive events (28.9%) in the 1219 HD patients using rosuvastatin versus (27.6%) in the 1220 HD patients using placebo (P = 0.44) during a median 4.5 years of follow-up. Due to the available trial data not confirming a clear benefit of statins therapy on vascular access patency, we carried out the present large-scale meta-analysis.…”

Section: Statins For Arteriovenous Fistulasmentioning

confidence: 99%

Impact of Statins on Arteriovenous Fistulas Outcomes: A Meta‐Analysis

Wan

Yang

et al. 2017

Ther Apher Dial

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Statins are effective lipid-lowering drugs with beneficial pleiotropic effects for vascular remodeling processes, statins may have a beneficial effect on the function of arteriovenous fistulas (AVFs) in hemodialysis (HD) patients. Therefore, we performed this systematic review to assess the protective effects of statin therapy in HD patients. The randomized controlled trials (RCTs) or quasiRCTs and retrospective cohort studies (RCS) of statin therapy for the function of AVFs in HD patients were searched from multiple databases. Relevant studies were screened according to predefined inclusion criteria and then pooled-analyses were performed using RevMan 5.2 software. One RCT and six RCS containing 20 246 HD patients were included in this meta-analysis, of whom 9847 were treated with statins and 10 399 were treated with placebo. Our meta-analysis showed that there was no significant difference between statins and placebo groups, with those who received statin therapy showing similar AVF failure rates compared to control (pooled risk ratio = 0.89; 95% CI, 0.70 to 1.12, P = 0.32), and there was obvious evidence of statistical heterogeneity (P = 0.005; I 2 = 68%). In addition, subgroup pooled analyses revealed that statin therapy did not ameliorate AVF failure in participants from the same racial background or similar sample size trials. There was no evidence that statins therapy could reduce the AVFs failure. However, due to methodological limitations and obvious statistical heterogeneity, high-quality, long-term and multicenter trials are required to fully elucidate the clinical value of statins administration for the outcomes of AVFs in HD patients.

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The Effect of Lowering LDL Cholesterol on Vascular Access Patency

Cited by 19 publications

References 28 publications

Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection

Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection

The pathogenesis of hemodialysis vascular access failure and systemic therapies for its prevention: Optimism unfulfilled

Impact of Statins on Arteriovenous Fistulas Outcomes: A Meta‐Analysis

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