INTRODUCTION: The use of statins in hemodialysis patients is a topic of ongoing research and debate. Patients with chronic kidney disease on hemodialysis constitute a large proportion of patients treated in the vascular surgery field. Clinical data of the protective statin effect on this group is scarce and conflicting results exist regarding cardiovascular, cerebrovascular and limb outcomes.


METHODS: We performed a thorough electronic search of the literature using PubMed and Embase databases to understand the relationship between statin effect and cardiovascular, limb outcomes and cerebrovascular outcomes. A narrative review was constructed, based on the obtained literature.


RESULTS: Although the use of statins in hemodialysis patients may provide cardiovascular benefits, the optimal dosage and safety profile of these medications in this population remain uncertain. A carefully evaluation of the risks and benefits of statins should be made based on each patient's specific requirements and circumstances.


CONCLUSION: The role of statins for patients with peripheral arterial disease who are on hemodialysis remains unclear. Further analyses should focus on this subgroup of dialysis patients, who are becoming more prevalent on the vascular surgery departments, allowing for an optimized treatment with better patient outcomes

Celso Nunes

Eduardo Silva

Juliana Sousa

Leonor Baldaia

Luis Orelhas

Manuel Fonseca

Miguel Silva

Vânia Oliveira

Angiologia e Cirurgia Vascular

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ANGIOLOGIA E CIRURGIA VASCULARPUBLICAÇÃO OFICIAL SPACVEffectiveness of statins on haemodialysis patients with concomitant peripheral arterial disease – a narrative reviewCelso Nunes       , Juliana Sousa, Vânia Oliveira, Eduardo Silva       , Leonor Baldaia       , Miguel Silva       , Luis Orelhas       , Manuel FonsecaAngiology and Vascular Surgery Department, Centro Hospitalar e Universitário de Coimbra, PortugaINTRODUCTION: The use of statins in hemodialysis patients is a topic of ongoing research and debate. Patients with chronic kidney disease on hemodialysis constitute a large proportion of patients treated in the vascular surgery field. Clinical data of the protective statin effect on this group is scarce and conflicting results exist regarding cardiovascular, cerebrovascular and limb outcomes. METHODS: We performed a thorough electronic search of the literature using PubMed and Embase databases to understand the relationship between statin effect and cardiovascular, limb outcomes and cerebrovascular outcomes. A narrative review was constructed, based on the obtained literature.RESULTS: Although the use of statins in hemodialysis patients may provide cardiovascular benefits, the optimal dosage and safety profile of these medications in this population remain uncertain. A carefully evaluation of the risks and benefits of statins should be made based on each patient's specific requirements and circumstances. CONCLUSION: The role of statins for patients with peripheral arterial disease who are on hemodialysis remains unclear. Further analyses should focus on this subgroup of dialysis patients, who are becoming more prevalent on the vascular surgery departments, allowing for an optimized treatment with better patient outcomes.Keywords: Statin; Hemodialysis; peripheral arterial disease; patient outcomes;ABSTRACTREVIEW ARTICLECorresponding Author: Celso Nunes | celsomiguel19@gmail.comPraceta Professor Mota Pinto, 3004-561 CoimbraAngiol Vasc Surg 2023;19(4):218-20DOI:  https://doi.org/10.48750/acv.552Submitted: May 9, 2023; Reviewed: May 23, 2023; Accepted: August 9, 2023INTRODUCTIONThe use of statins in hemodialysis patients is a topic of ongoing research and debate. Statins are medications that are commonly used to lower cholesterol levels in patients with or at risk for cardiovascular disease. However, hemodialysis patients often have unique metabolic profiles and comorbidities that may affect the efficacy and safety of statins. Patients with chronic kidney disease on hemodialysis constitute a large proportion of patients treated in the vascular surgery field, either for occlusive arterial disease of the lower limbs or for cerebrovascular disease. Clinical data of the protective statin effect on this group is scarce and conflicting results exist regarding cardiovascular, cerebrovascular and limb outcomes.METHODS We performed a thorough electronic search of the literature using PubMed and Embase databases to understand the relationship between statin effect and cardiovascular, limb and cerebrovascular outcomes. We used the following combination of key words in our search strategy ((statin effect) OR (LDL lowering effect) AND (hemodialysis) AND (vascular events) OR (limb revascularization) OR (cereberovascular)). 219Only articles in English published in the last 10 years were included. Titles and abstracts were screened and served to select full text for further assessment. Cross-referencing was performed.RESULTSAfter removal of duplicates, titles and abstracts screening and full text analysis, we included 11 articles in our review (Table).Article Year Type of study Endpoints Main conclusionBarylski et al(1) 2013 Meta-analysisImpact of statin therapy on cardiovascular events and death from all causes in CKD patientsNon-significant effect on death from all causes and stroke.Positive effect of reducing death from cardiac causes and cardiovascular events.Palmer et al(2) 2013 Systematic ReviewAssess the benefits and harms of statin use in adults who require dialysisNo beneficial effects on mortality or cardiovascular events and uncertain adverse effects.Nikolic et al(3) 2013 Meta-analysis Effects of statins on lipid profile of CKD PatientsLess beneficial effect in patients on dialysis with the trend to be less effective with longer duration of therapy.Wang et al(4) 2014 Meta-analysisOverall incidence of stroke, fatal stroke and hemorrhagic strokeA significant reduction in the incidence of overall stroke;No significant reduction in the incidence of fatal or hemorrhagic stroke.Sun et al(5) 2015 Meta-analysisEffect of statins on all cardiac events, cardiovascular deaths and all-cause mortality. (Dialisys Patients)No significant difference in reducing all-cause mortality and cardiovascular deaths.Reduced major cardiovascular events.Wang et al(6) 2015 Meta-analysisStroke, fatal stroke and hemorrhagic stroke incidences with high dose statin;Subgroup Dialysis/Renal transplant: no statistically significant reduction in all stroke incidences;Herrington et al(7)2016 Meta-analysis Cardiovascular events, stroke, and cause-specific mortalityNo evidence of benefit for any outcome in CKD5;Krane et al(8) 2016Post-trial follow-up of the 4D Study11-year cardiovascular outcomes, cause-specific mortality, and myopathy on hemodialysis patients with type 2 DiabetesNon-significant reduction in cardiovascular events and significant reductions in cardiac deaths and in all cardiac events combined.Messow et al(9) 2017 Meta-analysisCardiovascular events, death and all-cause mortality in CKD patientsNo evidence of benefit for any outcome in CKD5.Ghayda et al(10) 2021Umbrella Review of meta-analysis Statin effect on all-cause and cardiovascular mortality No benefit on dialysis patients.Lo et al(11) 2022Retrospective studyAll-cause death and the composite of endovascular therapy (EVT) and amputationAssociated with reductions in the risk of all-cause death, CV death, and the composite adverse limb outcome of endovascular treatment and amputation.Table 1. Summary of articles included in this reviewFrom the 11 articles, most concern effect of statins on Chronic Kidney Disease patients (CKD) of all stages and not only on hemodialysis patients. Only four articles(2,5,8,11) concerned specifically hemodialysis patients. While statin medication is effective in reducing cardiovascular events, stroke events and cardiovascular death on CKD patients, it becomes less clear when subgroup analyses are made for CKD stage 5 patients. Sun et al. found that statin therapy reduced major cardiovascular events, nevertheless, the relation with all-cause mortality and cardiovascular deaths had no beneficial effect.(5) Similarly, Wang et al. discovered a significant reduction in the incidence of overall stroke but no significant reduction in the incidence of fatal or hemorrhagic stroke.(6)Unfortunately, specific studies of the impact of carotid endarterectomy in this patient subgroup comparing outcomes in relation to statin therapy were not found in this research. After lower limb revascularization, a retrospective cohort found a protective association of statin therapy regarding the risk of all-cause death, cardiovascular death, and the composite adverse limb outcome of endovascular treatment and amputation (11).DISCUSSIONStatins have the potential to lower the risk of cardiovascular disease through multiple mechanisms, such as decreasing LDL-C levels, inhibiting platelet aggregation, improving endothelial function, reducing inflammation, and providing neuroprotection. Although, there have been safety and Effectiveness of statins for PAD patients on haemodialysis 220effectiveness concerns regarding the use of statins in dialysis patients, such as myalgia, myopathy, rhabdomyolysis, and liver disease.Several meta-analyses revealed that statins have no effect on cardiovascular outcomes, even when LDL is effectively lowered, since cardiovascular risk in the dialysis population, is owned to nonatherosclerotic cardiac events.(12) But even myocardial infarction and stroke are not significantly reduced, probably due to the different inherent cholesterol metabolism in these patients and its resistance to statins. Also, the statin procalcifying effect, through vitamin K metabolism which is known to inhibit vascular calcification and, is usually depleted in dialysis patients, can also play a role in accelerating the vascular calcifications.(13) Regarding the impact of statins on hemodialysis access, animal studies have consistently shown a protective effect. However, the translation of these findings to human trials has been more challenging. Some clinical studies have demonstrated benefits of statin therapy, indicating a reduction in stenosis and improved patency of vascular hemodialysis access.(15,16) Currently, while the American Heart Association does not have specific recommendations for statin therapy on dialysis patients, the Kidney Disease Improving Global Outcomes (KDIGO) organization recommends avoiding its initiation but not to stop therapy if the patient is already receiving it.  There is no clear consensus in the medical literature regarding the superiority of hydrophilic or lipophilic statins in hemodialysis patients. However, some studies have suggested that hydrophilic statins, such as pravastatin, may be preferred in patients with impaired kidney function because they are less dependent on renal excretion, reducing the risk of drug accumulation and potential side effects in patients with compromised kidney function.(17,18) A carefull evaluation of the risks and benefits of statins should be made based on each patient's specific requirements and circumstances. It is also still unknown whether statins may be advantageous for specific subgroups of dialysis patients with elevated LDL cholesterol and concomitant history of peripheral arterial occlusive disease. The long-term follow-up of the SHARP study will determine whether the reduction in major atherosclerotic events persists during the long-term follow-up.(14)CONCLUSIONAlthough the use of statins in hemodialysis patients may provide cardiovascular benefits, the optimal dosage and safety profile of these medications in this population remain uncertain. Further analyses should focus on this subgroup of dialysis patients, who are becoming more prevalent on the vascular surgery departments, allowing for an optimized treatment with better patient outcomes.Acknowledgements: NoneConflicts of interest: NoneFunding NoneREFERENCES1. Barylski M, Nikfar S, Mikhailidis DP, Toth PP, Salari P, Ray KK, et al. Lipid and Blood Pressure Meta-Analysis Collaboration Group. Statins decrease all-cause mortality only in CKD patients not requiring dialysis therapy--a meta-analysis of 11 randomized controlled trials involving 21,295 participants. Pharmacol Res. 2013;72:35-44.2. Nikolic D, Nikfar S, Salari P, Rizzo M, Ray KK, Pencina MJ,  et al. Lipid and Blood Pressure Meta-Analysis Collaboration Group. Effects of statins on lipid profile in chronic kidney disease patients: a meta-analysis of randomized controlled trials. Curr Med Res Opin. 2013;29:435-51.3. Palmer SC, Navaneethan SD, Craig JC, Johnson DW, Perkovic V, Nigwekar SU. HMG CoA reductase inhibitors (statins) for dialysis patients. Cochrane Database Syst Rev. 2013;(9):CD0042894. Wang W, Zhang B. Statins for the prevention of stroke: a meta-analysis of randomized controlled trials. PLoS One. 2014;9:e92388.5. Sun L, Zou L, Chen M, Liu B. Meta-analysis of statin therapy in maintenance dialysis patients. Ren Fail. 2015;37:1149-56.6. Wang J, Chen D, Li DB, Yu X, Shi GB. Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention: A meta-analysis. Medicine (Baltimore). 2016;95:e4950.7. Cholesterol Treatment Trialists' (CTT) Collaboration; Herrington WG, Emberson J, Mihaylova B, Blackwell L, Reith C, Solbu MD, et al.  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. Lancet Diabetes Endocrinol. 2016;4:829-39. 8. Krane V, Schmidt KR, Gutjahr-Lengsfeld LJ, Mann JF, März W, Swoboda F, et al. 4D Study Investigators (the German Diabetes and Dialysis Study Investigators). Long-term effects following 4 years of randomized treatment with atorvastatin in patients with type 2 diabetes mellitus on hemodialysis. Kidney Int. 2016;89:1380-79. Messow CM, Isles C. Meta-analysis of statins in chronic kidney disease: who benefits? QJM. 2017;110:493-50010. Ghayda RA, Lee JY, Yang JW, Han CH, Jeong GH, Yoon S, et al.  The effect of statins on all-cause and cardiovascular mortality in patients with non-dialysis chronic kidney disease, patients on dialysis, and kidney transplanted recipients: an umbrella review of meta-analyses. Eur Rev Med Pharmacol Sci. 2021;25:2696-71011. Lo HY, Lin YS, Lin DS, Lee JK, Chen WJ. Association of Statin Therapy With Major Adverse Cardiovascular and Limb Outcomes in Patients With End-stage Kidney Disease and Peripheral Artery Disease Receiving Maintenance Dialysis. JAMA Netw Open. 2022;5:e2229706. 12. Wheeler DC, London GM, Parfrey PS, Block GA, Correa-Rotter R, Dehmel B, et al. EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial Investigators: Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: The Evaluation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial. J Am Heart Assoc. 2015;4:e000570.13. Caluwé R, Pyfferoen L, De Boeck K, De Vriese AS: The effects of vitamin K supplementation and vitamin K antagonists on progression of vascular calcification: Ongoing randomized controlled trials. Clin Kidney J. 2016;9:273–9 14. Sukkar L, Talbot B, Jun M, Dempsey E, Walker R, Hooi L, et al. Protocol for the Study of Heart and Renal Protection-Extended Review: Additional 5-Year Follow-up of the Australian, New Zealand, and Malaysian SHARP Cohort. Can J Kidney Health Dis. 2019;6:2054358119879896. 15. Suh D, Amendola MF, Reeves M, Wolfe L, Posner M, Davis R. Statins Protect against Thrombosis of Cannulated Radiocephalic Fistulas in Diabetic Patients. Ann Vasc Surg. 2021;75:280-616. Chang HH, Chang YK, Lu CW, Huang CT, Chien CT, Hung KY. Statins Improve Long Term Patency of Arteriovenous Fistula for Hemodialysis. Sci Rep. 2016;6:22197.17. Kang MH, Kim W, Kim JS, Jeong KH, Jeong MH, Hwang JY, et al. Hydrophilic Versus Lipophilic Statin Treatments in Patients With Renal Impairment After Acute Myocardial Infarction. J Am Heart Assoc. 2022;11:e024649. 18. Climent E, Benaiges D, Pedro-Botet J. Hydrophilic or Lipophilic Statins? Front Cardiovasc Med. 2021;8:687585.Nunes et al.

Effectiveness of statins on haemodialysis patients with concomitant peripheral arterial disease – a narrative review

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Effectiveness of statins on haemodialysis patients with concomitant peripheral arterial disease – a narrative review

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