Department of Clinical Pharmacy, School of Pharmacy, University of Colorado, Aurora, CO 80045, USA.
Pharmacotherapy. 2010 Aug;30(8):823-9. doi: 10.1592/phco.30.8.823.
In the general population, dyslipidemia is an established independent risk factor for cardiovascular disease. In patients with end-stage renal disease (ESRD), comorbid cardiovascular disease is present at alarming rates, and those who require hemodialysis and have cardiovascular disease continue to have a high mortality rate. Lipid abnormalities associated with chronic kidney disease (CKD) vary depending on the stage of disease (stages 1-5), but low-density lipoprotein cholesterol (LDL) has been established as the primary lipid treatment target. Guidelines support an LDL level of less than 100 mg/dl in patients with all stages of CKD, except when the triglyceride level is above 500 mg/dl. As patients progress to stage 5 CKD (ESRD with hemodialysis), the high triglyceride, low high-density lipoprotein cholesterol, and increased lipoprotein(a) levels of the early stages become more pronounced, with increases in small dense LDL particles; however, total cholesterol and LDL values remain normal or decrease. In patients undergoing hemodialysis, lipid abnormalities are driven by an increase in hepatic secretion and delayed catabolism of very low-density lipoproteins, as well as a reduction in lipoprotein lipase and hepatic lipase. Epidemiologic data support the role of cholesterol lowering as a means to lower cardiovascular events in the hemodialysis population. We conducted a literature search of various databases (1966-September 2009) to identify relevant clinical trials that evaluated the efficacy and safety of multiple lipid-lowering agents for the treatment of dyslipidemia in patients with ESRD requiring hemodialysis. Only those trials that used clinical primary end points of coronary heart disease (e.g., cardiovascular death, myocardial infarction, stroke) were included in this review. Evidence demonstrates that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy (i.e., atorvastatin and rosuvastatin) significantly reduces surrogate cardiovascular markers, particularly LDL, in patients with ESRD requiring hemodialysis; however, no statin has proved to reduce cardiovascular morbidity or mortality in this population. Trials evaluating omega-3 fatty acids did not show significant reductions in LDL or cardiovascular events in this population. Clinicians should appreciate these limitations when deciding whether to continue lipid-lowering pharmacotherapy in these patients, depending on their overall cardiovascular risk assessment.
在普通人群中，血脂异常是心血管疾病的一个既定独立危险因素。在终末期肾病（ESRD）患者中，合并心血管疾病的发病率很高，需要进行血液透析且患有心血管疾病的患者继续存在高死亡率。与慢性肾脏病（CKD）相关的脂质异常随疾病阶段（1-5 期）而变化，但已证实低密度脂蛋白胆固醇（LDL）是主要的脂质治疗靶点。指南支持所有 CKD 阶段的患者 LDL 水平低于 100mg/dl，除非甘油三酯水平高于 500mg/dl。随着患者进展到 CKD 5 期（ESRD 伴血液透析），早期的高甘油三酯、低高密度脂蛋白胆固醇和脂蛋白（a）水平增加，小而密 LDL 颗粒增加；然而，总胆固醇和 LDL 值保持正常或降低。在进行血液透析的患者中，脂质异常是由于极低密度脂蛋白的肝分泌增加和代谢延迟、脂蛋白脂酶和肝脂酶减少所致。流行病学数据支持降低胆固醇作为降低血液透析人群心血管事件的一种手段。我们对各种数据库（1966 年-2009 年 9 月）进行了文献检索，以确定评估多种降脂药物治疗需要血液透析的 ESRD 患者血脂异常的疗效和安全性的相关临床试验。只有那些使用冠心病（例如，心血管死亡、心肌梗死、中风）的临床主要终点的试验被纳入本综述。证据表明，3-羟基-3-甲基戊二酰基辅酶 A 还原酶抑制剂（他汀类药物）治疗（即阿托伐他汀和罗苏伐他汀）可显著降低需要血液透析的 ESRD 患者的替代心血管标志物，特别是 LDL；然而，没有他汀类药物已被证明可降低该人群的心血管发病率或死亡率。评估ω-3 脂肪酸的试验并未显示该人群 LDL 或心血管事件的显著减少。临床医生在决定是否继续对这些患者进行降脂药物治疗时，应根据其总体心血管风险评估来考虑这些局限性。
