Introduction

The 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)). Only 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.

Results

After removal of duplicates, titles and abstracts screening and full text analysis, we included 11 articles in our review (Table).

From 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.

Discussion

Statins 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 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

Conclusion

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. 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:

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Conflicts of interest

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Funding

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