Wetmore James B, Shireman Theresa I
Department of Medicine, Division of Nephrology and Hypertension, University of Kansas School of Medicine, Kansas City, KS 66160, USA.
Am J Kidney Dis. 2009 Mar;53(3):457-66. doi: 10.1053/j.ajkd.2008.07.037. Epub 2008 Nov 20.
Several classes of medications have been shown to decrease all-cause and cardiovascular mortality in the general population. However, dialysis patients have been systematically excluded from these large trials, and the benefits of angiotensin-converting enzyme (ACE) inhibitors, adrenergic beta antagonists (beta-blockers), and calcium channel blockers (CCBs) are uncertain in this population.
We performed a systematic review using the MEDLINE database (inception to October 14, 2007) to identify studies.
SETTING & POPULATION: Incident and prevalent dialysis patients.
English-language randomized controlled trials (RCTs) and observational studies investigating the use of ACE inhibitors, beta-blockers, and CCBs in humans.
ACE-inhibitor, beta-blocker, and CCB administration.
Decreases in all-cause and cardiovascular mortality and cardiovascular morbidity.
674 reports yielded 13 suitable reports for ACE inhibitors, 12 for beta-blockers, and 6 for CCBs. Because most studies investigated more than 1 class of drug, there were 17 unique reports; 2 were RCTs, 1 was a "pseudo-RCT," and 14 were observational studies. Meta-analysis was not possible because of the heterogeneity of studies. There is considerable discrepancy in the literature about the utility of these agents. ACE inhibitors have not consistently shown survival benefits in either the single RCT or observational studies. beta-Blockers showed mortality benefit in only 1 large cohort study plus an RCT of patients with congestive heart failure, but results were not duplicated in other studies; the magnitude of beta-blocker benefit after myocardial infarction was similar in dialysis and nondialysis individuals in another study. CCBs show the most consistent benefits, albeit only from observational studies, of the classes examined.
Several major limitations were present, including a paucity of RCTs and nonrandom treatment assignment and lack of data for longitudinal medication exposure in observational studies.
Despite considerable uncertainty about the benefits and risks in this population, for individuals with well-established traditional indications for these medications, refraining from prescribing them may be imprudent at this time. However, RCTs, as well as well-designed observational studies that adjust for nonrandom treatment assignment and longitudinal drug exposure, are needed.
几类药物已被证明可降低普通人群的全因死亡率和心血管死亡率。然而,透析患者被系统性地排除在这些大型试验之外,血管紧张素转换酶(ACE)抑制剂、肾上腺素能β受体拮抗剂(β受体阻滞剂)和钙通道阻滞剂(CCB)在该人群中的益处尚不确定。
我们使用MEDLINE数据库(从创建到2007年10月14日)进行了一项系统评价以识别研究。
新发病例和现患透析患者。
调查人类使用ACE抑制剂、β受体阻滞剂和CCB的英文随机对照试验(RCT)和观察性研究。
给予ACE抑制剂、β受体阻滞剂和CCB。
全因死亡率和心血管死亡率的降低以及心血管发病率。
674篇报告产生了13篇关于ACE抑制剂的合适报告、12篇关于β受体阻滞剂的报告和6篇关于CCB的报告。由于大多数研究调查了不止一类药物,因此有17篇独特的报告;2篇为RCT,1篇为“伪RCT”,14篇为观察性研究。由于研究的异质性,无法进行荟萃分析。关于这些药物的效用,文献中存在相当大的差异。ACE抑制剂在单一RCT或观察性研究中均未始终显示出生存益处。β受体阻滞剂仅在1项大型队列研究以及1项充血性心力衰竭患者的RCT中显示出死亡率益处,但在其他研究中结果未被重复;在另一项研究中,透析和非透析个体心肌梗死后β受体阻滞剂的益处程度相似。在所研究的类别中,CCB显示出最一致的益处,尽管仅来自观察性研究。
存在几个主要局限性,包括RCT数量不足、非随机治疗分配以及观察性研究中缺乏纵向药物暴露数据。
尽管该人群的益处和风险存在相当大的不确定性,但对于有明确传统用药指征的个体,此时不处方这些药物可能是不明智的。然而,需要进行RCT以及针对非随机治疗分配和纵向药物暴露进行调整的精心设计的观察性研究。